Search results for: tumor cell lines

Authors: Neha P. Amin, Maliha Zainib, Sean Parker, Malcolm Mattes

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Purpose/Objectives: Combination immunotherapy (IT) and radiation therapy (RT) is an actively growing field of clinical investigation due to promising findings of synergistic effects from immune-mediated mechanisms observed in preclinical studies and clinical data from case reports of abscopal effects. While there are many ongoing trials of combined IT-RT, there are still limited data on toxicity and outcome optimization regarding RT dose, fractionation, and sequencing of RT with IT. Nivolumab (NIVO), an anti-PD-1 monoclonal antibody, has been rapidly adopted in the clinic over the past 2 years, resulting in more patients being considered for concurrent RT-NIVO. Knowledge about the toxicity profile of combined RT-NIVO is important for both the patient and physician when making educated treatment decisions. The acute toxicity profile of concurrent RT-NIVO was analyzed in this study. Materials/Methods: A retrospective review of all consecutive patients who received NIVO from 1/2015 to 5/2017 at 4 separate centers within two separate institutions was performed. Those patients who completed a course of RT from 1 day prior to initial NIVO infusion through 1 month after last NIVO infusion were considered to have received concurrent therapy and included in the subsequent analysis. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed acute toxicities within 3 months of RT completion. Results: Among 261 patients who received NIVO, 46 (17.6%) received concurrent RT to 67 different sites. The median f/u was 3.3 (.1-19.8) months, and 11/46 (24%) were still alive at last analysis. The most common histology, RT prescription, and treatment site included non-small cell lung cancer (23/46, 50%), 30 Gy in 10 fractions (16/67, 24%), and central thorax/abdomen (26/67, 39%), respectively. 79% (53/67) of irradiated sites were treated with 3D-conformal technique and palliative dose-fractionation. Grade 3, 4, and 5 toxicities were experienced by 11, 1, and 2 patients, respectively. However all grade 4 and 5 toxicities were outside of the irradiated area and attributed to the NIVO alone, and only 4/11 (36%) of the grade 3 toxicities were attributed to the RT-NIVO. The irradiated site in these cases included the brain [2/10 (20%)] and central thorax/abdomen [2/19 (10.5%)], including one unexpected grade 3 pancreatitides following stereotactic body RT to the left adrenal gland. Conclusions: Concurrent RT-NIVO is generally well tolerated, though with potentially increased rates of severe toxicity when irradiating the lung, abdomen, or brain. Pending more definitive data, we recommend counseling patients on the potentially increased rates of side effects from combined immunotherapy and radiotherapy to these locations. Future prospective trials assessing fractionation and sequencing of RT with IT will help inform combined therapy recommendations.

Keywords: combined immunotherapy and radiation, immunotherapy, Nivolumab, toxicity of concurrent immunotherapy and radiation

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Authors: Strahinja Kovačević, Lidija Jevrić, Miloš Kuzmanović, Sanja Podunavac-Kuzmanović

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In this paper, various derivatives of benzimidazole have been evaluated against Gram-negative bacteria Escherichia coli. For all investigated compounds the minimum inhibitory concentration (MIC) was determined. Quantitative structure-activity relationships (QSAR) attempts to find consistent relationships between the variations in the values of molecular properties and the biological activity for a series of compounds so that these rules can be used to evaluate new chemical entities. The correlation between MIC and some absorption, distribution, metabolism and excretion (ADME) parameters was investigated, and the mathematical models for predicting the antibacterial activity of this class of compounds were developed. The quality of the multiple linear regression (MLR) models was validated by the leave-one-out (LOO) technique, as well as by the calculation of the statistical parameters for the developed models and the results are discussed on the basis of the statistical data. The results of this study indicate that ADME parameters have a significant effect on the antibacterial activity of this class of compounds. Principal component analysis (PCA) and agglomerative hierarchical clustering algorithms (HCA) confirmed that the investigated molecules can be classified into groups on the basis of the ADME parameters: Madin-Darby Canine Kidney cell permeability (MDCK), Plasma protein binding (PPB%), human intestinal absorption (HIA%) and human colon carcinoma cell permeability (Caco-2).

Keywords: benzimidazoles, QSAR, ADME, in silico

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Authors: Mojtaba Noghabaei, Khashayar Asadi, Kevin Han

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Simultaneous Localization and Mapping (SLAM) technology has recently attracted the attention of construction companies for real-time performance monitoring. To effectively use SLAM for construction performance monitoring, SLAM results should be registered to a Building Information Models (BIM). Registring SLAM and BIM can provide essential insights for construction managers to identify construction deficiencies in real-time and ultimately reduce rework. Also, registering SLAM to BIM in real-time can boost the accuracy of SLAM since SLAM can use features from both images and 3d models. However, registering SLAM with the BIM in real-time is a challenge. In this study, a novel SLAM platform named Model-Based SLAM (MB-SLAM) is proposed, which not only provides automated registration of SLAM and BIM but also improves the localization accuracy of the SLAM system in real-time. This framework improves the accuracy of SLAM by aligning perspective features such as depth, vanishing points, and vanishing lines from the BIM to the SLAM system. This framework extracts depth features from a monocular camera’s image and improves the localization accuracy of the SLAM system through a real-time iterative process. Initially, SLAM can be used to calculate a rough camera pose for each keyframe. In the next step, each SLAM video sequence keyframe is registered to the BIM in real-time by aligning the keyframe’s perspective with the equivalent BIM view. The alignment method is based on perspective detection that estimates vanishing lines and points by detecting straight edges on images. This process will generate the associated BIM views from the keyframes' views. The calculated poses are later improved during a real-time gradient descent-based iteration method. Two case studies were presented to validate MB-SLAM. The validation process demonstrated promising results and accurately registered SLAM to BIM and significantly improved the SLAM’s localization accuracy. Besides, MB-SLAM achieved real-time performance in both indoor and outdoor environments. The proposed method can fully automate past studies and generate as-built models that are aligned with BIM. The main contribution of this study is a SLAM framework for both research and commercial usage, which aims to monitor construction progress and performance in a unified framework. Through this platform, users can improve the accuracy of the SLAM by providing a rough 3D model of the environment. MB-SLAM further boosts the application to practical usage of the SLAM.

Keywords: perspective alignment, progress monitoring, slam, stereo matching.

Procedia PDF Downloads 219

Authors: P. Joris, E. Lombard, X. Cameleyre, G. Navarro, A. Paillet, N. Gorret, S. E. Guillouet

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Today, on the international space station, multiple supplies are needed per year to supply food and spare parts and to take out waste. But as it is planned to go longer and further into space these supplies will no longer be possible. The astronaut life support system must be able of continuously transform waste into valuable compounds. Two types of production were identified as critical and could be be supplemented by microorganisms. On the one hand, since microgravity causes rapid muscle loss, single cell proteins (SCPs) could be used as protein rich feed or food. On the other hand, having enough building materials to build an advanced habitat will not be possible only by transporting space goods from earth to mars for example. The bacterium Cupriavidus. necator is well known for its ability to produce a large amount of proteins or of polyhydroxyalkanoate biopolymers (PHAs) depending on its implementation. By coupling the life support system to a 3D-printer, astronauts could be supplied with an unlimited amount of building materials. Additionally, based on the design of the life support system, waste streams have been identified: urea from the crew urine and volatile fatty acids (VFAs) from a first stage of organic waste (excrement and food waste) treatment through anaerobic digestion. Thus, the objective of this, within the Spaceship.Fr project, was to demonstrate the feasibility of producing SCPs and PHAs from VFAs and urea in bioreactor. Because life support systems operate continuously as loops, continuous culture experiments were chosen and the effect of the bioreactor dilution rate on biomass composition was investigated. Total transformation of the carbon source into biomass with high SCP or PHA content was achieved in all cases. We will present the transformation performances of VFAs and urea by the bacteria in bioreactor in terms of titers, yields and productivities but also in terms of the quality of SCP and PHA produced, nucleic acid content. We will further discuss the envisioned integration of our process within life support systems.

Keywords: life support system, space travel, waste treatment, single cell proteins, polyhydroxyalkanoates, bioreactor

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Authors: Sara R. Knigge, Sugat R. Tuladhar, Alexander Becker, Tobias Schilling, Birgit Glasmacher

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Commercially available mechanical or biological heart valve prostheses both tend to fail long-term due to thrombosis, calcific degeneration, infection, or immunogenic rejection. Moreover, these prostheses are non-viable and do not grow with the patients, which is a problem for young patients. As a result, patients often need to undergo redo-operations. Tissue-engineered (TE) heart valves based on degradable electrospun fiber scaffolds represent a promising approach to overcome these limitations. Such scaffolds need sufficient mechanical properties to withstand the hydrodynamic stress of intracardiac hemodynamics. Additionally, the scaffolds should be colonized by autologous or homologous cells to facilitate the in vivo remodeling of the scaffolds to a viable structure. This study investigates how process parameters of electrospinning and degradation affect the mechanical properties of electrospun scaffolds made of FDA-approved, biodegradable polymer polycaprolactone (PCL). Fiber mats were produced from a PCL/tetrafluoroethylene solution by electrospinning. The e-spinning process was varied in terms of scaffold thickness, fiber diameter, fiber orientation, and fiber interconnectivity. The morphology of the fiber mats was characterized with a scanning electron microscope (SEM). The mats were degraded in different solutions (cell culture media, SBF, PBS and 10 M NaOH-Solution). At different time points of degradation (2, 4 and 6 weeks), tensile and cyclic loading tests were performed. Fresh porcine pericardium and heart valves served as a control for the mechanical assessment. The progression of polymer degradation was quantified by SEM and differential scanning calorimetry (DSC). Primary Human aortic endothelial cells (HAECs) and Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) were seeded on the fiber mats to investigate the cell colonization potential. The results showed that both the electrospinning parameters and the degradation significantly influenced the mechanical properties. Especially the fiber orientation has a considerable impact and leads to a pronounced anisotropic behavior of the scaffold. Preliminary results showed that the polymer became strongly more brittle over time. However, the embrittlement can initially only be detected in the mechanical test. In the SEM and DSC investigations, neither morphological nor thermodynamic changes are significantly detectable. Live/Dead staining and SEM imaging of the cell-seeded scaffolds showed that HAECs and iPSC-ECs were able to grow on the surface of the polymer. In summary, this study's results indicate a promising approach to the development of a TE aortic heart valve based on an electrospun scaffold.

Keywords: electrospun scaffolds, long-term polymer degradation, mechanical behavior of electrospun PCL, tissue engineered aortic heart valve

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Authors: Anupuma Raina, Ajay Parkash

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In forensic investigation, DNA analysis helps in the identification of a particular individual under investigation. A set of Short Tandem Repeats loci are widely used for individualization at a molecular level in forensic testing. STRs with tetrameric repeats of DNA are highly polymorphic and widely used for forensic DNA analysis. Identification of an individual became challenging for forensic examiners after Hematopoietic Stem Cell Transplantation. HSCT is a well-accepted and life-saving treatment to treat malignant and nonmalignant diseases. It involves the administration of healthy donor stem cells to replace the patient’s own unhealthy stem cells. A successful HSCT results in complete donor-derived cells in a patient’s hematopoiesis and hence have the capability to change the genetic makeup of the patient. Although an individual who has undergone HSCT and then committed a crime is a very rare situation, but not impossible. Keeping such a situation in mind, various biological samples like blood, buccal swab, and hair follicle were collected and studied after a certain interval of time after HSCT. Blood was collected from both the patient and the donor before the transplant. The DNA profile of both was analyzed using a short tandem repeat kit for autosomal chromosomes. Among all exhibits studied, only hair follicles were found to be the most suitable biological exhibit, as no donor DNA profile was observed for up to 90 days of study.

Keywords: chimerism, HSCT, STRs analysis, forensic identification

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Authors: Otilia Ruxandra Vasile, Ecaterina Andronescu, Cristina Daniela Ghitulica, Bogdan Stefan Vasile, Roxana Trusca, Eugeniu Vasile, Alina Maria Holban, Carmen Mariana Chifiriuc, Florin Iordache, Horia Maniu

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Engineered powders offer great promise in several applications, but little information is known about cytotoxicity effects. The aim of the current study was the synthesis and cytotoxicity examination of silver powders using pyrosol method at temperatures of 600°C, 650°C and 700°C, respectively sol-gel method and calcinations at 500°C, 600°C, 700°C and 800°C. We have chosen to synthesize and examine silver particles cytotoxicity due to its use in biological applications. The synthesized Ag powders were characterized from the structural, compositional and morphological point of view by using XRD, SEM, and TEM with SAED. In order to determine the influence of the synthesis route on Ag particles cytotoxicity, different sizes of micro and nanosilver synthesized powders were evaluated for their potential toxicity. For the study of their cytotoxicity, cell cycle and apoptosis have been done analysis through flow cytometry on human colon carcinoma cells and mesenchymal stem cells and through the MTT assay, while the viability and the morphological changes of the cells have been evaluated by using cloning studies. The results showed that the synthesized silver nanoparticles have displayed significant cytotoxicity effects on cell cultures. Our synthesized silver powders were found to present toxicity in a synthesis route and time-dependent manners for pyrosol synthesized nanoparticles; whereas a lower cytotoxicity has been measured after cells were treated with silver nanoparticles synthesized through sol-gel method.

Keywords: Ag, cytotoxicity, pyrosol method, sol-gel method

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Authors: Zhuohan Li, Jing Yang, Yaoyuan Cui

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The gut-brain axis (GBA), a communication network between gut microbiota and the brain, benefits for investigation of brain diseases. Currently, organ chips are considered one of the potential tools for GBA research. However, most of the available GBA chips have limitations in replicating the three-dimensional (3D) growth environment of cells and lack the required cell types for barrier function. In the present study, a microfluidic chip was developed for GBA interaction. Blood-brain barrier (BBB) module was prepared with HBMEC, HBVP, U87 cells and decellularized matrix (dECM). Intestinal epithelial barrier (IEB) was prepared with Caco-2 and vascular endothelial cells and dECM. GBA microfluidic device was integrated with IEB and BBB modules using 3D printing interconnecting microchannel scaffolds. BBB and IEB interaction on this GBA chip were evaluated with lipopolysaccharide (LPS) exposure. The present GBA chip achieved multicellular three-dimensional cultivation. Compared with the co-culture cell model in the transwell, fluorescein was absorbed more slowly by 5.16-fold (IEB module) and 4.69-fold (BBB module) on the GBA chip. Accumulation of Rhodamine 123 and Hoechst33342 was dramatically decreased. The efflux function of transporters on IEB and BBB was significantly increased on the GBA chip. After lipopolysaccharide (LPS) disrupted the IEB, and then BBB dysfunction was further observed, which confirmed the interaction between IEB and BBB modules. These results demonstrated that this GBA chip may offer a promising tool for gut-brain interaction study.

Keywords: decellularized matrix, gut-brain axis, organ-on-chip, three-dimensional printing.

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Authors: S. Wiak, L. Szymanski, Z. Kolacinski, G. Raniszewski, L. Pietrzak, Z. Staniszewska

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The term ‘cancer’ is given to a collection of related diseases that may affect any part of the human body. It is a pathological behaviour of cells with the potential to undergo abnormal breakdown in the processes that control cell proliferation, differentiation, and death of particular cells. Although cancer is commonly considered as modern disease, there are beliefs that drastically growing number of new cases can be linked to the extensively prolonged life expectancy and enhanced techniques for cancer diagnosis. Magnetic hyperthermia therapy is a novel approach to cancer treatment, which may greatly contribute to higher efficiency of the therapy. Employing carbon nanotubes as nanocarriers for magnetic particles, it is possible to decrease toxicity and invasiveness of the treatment by surface functionalisation. Despite appearing in recent years, magnetic particle hyperthermia has already become of the highest interest in the scientific and medical environment. The reason why hyperthermia therapy brings so much hope for future treatment of cancer lays in the effect that it produces in malignant cells. Subjecting them to thermal shock results in activation of numerous degradation processes inside and outside the cell. The heating process initiates mechanisms of DNA destruction, protein denaturation and induction of cell apoptosis, which may lead to tumour shrinkage, and in some cases, it may even cause complete disappearance of cancer. The factors which have the major impact on the final efficiency of the treatment include temperatures generated inside the tissues, time of exposure to the heating process, and the character of an individual cancer cell type. The vast majority of cancer cells is characterised by lower pH, persistent hypoxia and lack of nutrients, which can be associated to abnormal microvasculature. Since in healthy tissues we cannot observe presence of these conditions, they should not be seriously affected by elevation of the temperature. The aim of this work is to investigate the influence of iron content in iron filled Carbon Nanotubes on the desired nanoparticles for cancer therapy. In the article, the development and demonstration of the method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nanocontainers. The methodology of the production carbon- ferromagnetic nanocontainers (FNCs) includes the synthesis of carbon nanotubes, chemical, and physical characterization, increasing the content of a ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. The ferromagnetic nanocontainers were synthesised in CVD and microwave plasma system. The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013.

Keywords: hyperthermia, carbon nanotubes, cancer colon cells, radio frequency field

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Authors: Debasmita Dubey, Rajesh Kumar Meher, Smruti Pragya Samal, Pradeep Kumar Naik

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Background: To determine antioxidant properties and anticancer activity by ROS and mitochondrial transmembrane potential mediated apoptosis against MCF7, MDA-MB-231, cell line. Methods: Leaf sample was extracted using methanol by microwave digestion technique. The antioxidant properties of the methanolic extract were determined by a DPPH scavenging assay. In vitro anticancer activity, mitochondrial transmembrane potential, apoptosis activity and DNA fragmentation study, as well as intracellular ROS activity of most potential leaf extract, were also determined by using the MDA-MB-231cell line. In vivo animal toxicity study was carried out using mice model. Results: Methanolic leaf extract has shown the highest antioxidant, as well as anticancer activity, is based on the assay conducted. For the identification of active phytochemicals from methanolic extract, High-resolution mass spectroscopy-LCMS was used. In vitro cytotoxicity study against MCF-7 and MDA-MB-231 cell line and IC 50 value was found to be 37.5µg/ml. From histopathological studies, no toxicity in liver and kidney tissue was identified. Conclusion: This plant tuber can be used as a regular diet to reduce the chance of breast cancer. Further, more studies should be conducted to isolate and identify the responsible compound.

Keywords: human breast adenocarcinoma, ROS, mitochondrial transmembrane, apoptosis

Procedia PDF Downloads 113

Authors: Jannika Dombrowski, Sabine Ambros, Ulrich Kulozik

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Due to the increasing popularity of healthy products, probiotics are still of rising importance in food manufacturing. With the aim to amplify the field of probiotic application to non-chilled products, the cultures have to be preserved by drying. Microwave drying has proved to be a suitable technique to achieve relatively high survival rates, resulting from drying at gentle temperatures, among others. However, diffusion limitation due to compaction of cell suspension during drying can prolong drying times as well as deteriorate product properties (grindability, rehydration performance). Therefore, we aimed to embed probiotics in an aerated matrix of whey proteins (surfactants) and di-/polysaccharides (foam stabilization, probiotic protection) during drying. As a result of the manifold increased inner surface of the cell suspension, drying performance was enhanced significantly as compared to non-foamed suspensions. This work comprises investigations on suitable foam matrices, being stable under vacuum (variation of protein concentration, type and concentration of di-/polysaccharide) as well as development of an applicable microwave drying process in terms of microwave power, chamber pressure and maximum product temperatures. Performed analyses included foam characteristics (overrun, drainage, firmness, bubble sizes), and properties of the dried cultures (survival, activity). In addition, efficiency of the drying process was evaluated.

Keywords: foam structure, microwave drying, polysaccharides, probiotics

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Authors: Azza El-Medany, Jamila El-Medany

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Residential and agricultural pesticide use is widespread in the world. Their extensive and indiscriminative use, in addition with their ability to interact with biological systems other than their primary targets constitute a health hazards to both humans and animals. The toxic effects of pesticides include alterations in metabolism; there is a lack of knowledge that organophosphates can cause pancreatic toxicity. The primary goal of this work is to study the effects of chronic exposure to Diazinon an organophosphate used in agriculture on pancreatic tissues and evaluate the ameliorating effect of Mesna as antioxidant on the toxicity of Diazinon on pancreatic tissues.40 adult male rats, their weight ranged between 300-350 g. The rats were classified into three groups; control (10 rats) was received corn oil at a dose of 1 0 mg/kg/day by gavage once a day for 2 months. Diazinon (15 rats) was received Diazinon at a dose of 10 mg/kg/day dissolved in corn oil by gavage once a day for 2 months. Treated group (15 rats), were received Mesna 180mg/kg once a week by gavage 15 minutes before administration of Diazinon for 2 months. At the end of the experiment, animals were anesthetized, blood samples were taken by cardiac puncture for glucose and insulin assays and pancreas was removed and divided into 3 portions; first portion for histopathological study; second portion for ultrastructural study; third portion for biochemical study using Elisa Kits including determination of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), myeloperoxidase activity (MPO), interleukin 1β (IL-1β). A significant increase in the levels of MDA, TNF-α, MPO activity, IL-1β, serum glucose levels in the toxicated group with Diazinon were observed, while a significant reduction was noticed in GSH in serum insulin levels. After treatment with Mesna a significant reduction was observed in the previously mentioned parameters except that there was a significant rise in GSH in insulin levels. Histopathological and ultra-structural studies showed destruction in pancreatic tissues and β cells were the most affected cells among the injured islets as compared with the control group. The current study try to spot light about the effects of chronic exposure to pesticides on vital organs as pancreas also the role of oxidative stress that may be induced by them in evoking their toxicity. This study shows the role of antioxidant drugs in ameliorating or preventing the toxicity. This appears to be a promising approach that may be considered as a complementary treatment of pesticide toxicity.

Keywords: Diazinon, reduced glutathione, myeloperoxidase activity, tumor necrosis factor α, Mesna

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Authors: M. I. Tyletc, O. I. Podgornya, T. G. Shaposhnikova, S. V. Shabelnikov, A. G. Mittenberg, M. A. Daugavet

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Ascidiacea is the most numerous class of the Tunicata subtype. These chordates' distinctive feature of the anatomical structure is a tunic consisting of cellulose fibrils, protein molecules, and single cells. The mechanisms of the tunic formation are not known in detail; tunic formation could be used as the model system for studying the interaction of cells with the extracellular matrix. Our model species is the ascidian Styela rustica, which is prevalent in benthic communities of the White Sea. As previously shown, the tunic formation involves morula blood cells, which contain the major 48 kDa protein p48. P48 participation in the tunic formation was proved using antibodies against the protein. The nature of the protein and its function remains unknown. The current research aims to determine the amino acid sequence of p48, as well as to clarify its role in the tunic formation. The peptides that make up the p48 amino acid sequence were determined by mass spectrometry. A search for peptides in protein sequence databases identified sequences homologous to p48 in Styela clava, Styela plicata, and Styela canopus. Based on sequence alignment, their level of similarity was determined as 81-87%. The correspondent sequence of ascidian Styela canopus was used for further analysis. The Styela rustica p48 sequence begins with a signal peptide, which could indicate that the protein is secretory. This is consistent with experimentally obtained data: the contents of morula cells secreted in the tunic matrix. The isoelectric point of p48 is 9.77, which is consistent with the experimental results of acid electrophoresis of morula cell proteins. However, the molecular weight of the amino acid sequence of ascidian Styela canopus is 103 kDa, so p48 of Styela rustica is a shorter homolog. The search for conservative functional domains revealed the presence of two Ca-binding EGF-like domains, thrombospondin (TSP1) and tyrosinase domains. The p48 peptides determined by mass spectrometry fall into the region of the sequence corresponding to the last two domains and have amino acid substitutions as compared to Styela canopus homolog. The tyrosinase domain (pfam00264) is known to be part of the phenoloxidase enzyme, which participates in melanization processes and the immune response. The thrombospondin domain (smart00209) interacts with a wide range of proteins, and is involved in several biological processes, including coagulation, cell adhesion, modulation of intercellular and cell-matrix interactions, angiogenesis, wound healing and tissue remodeling. It can be assumed that the tyrosinase domain in p48 plays the role of the phenoloxidase enzyme, and TSP1 provides a link between the extracellular matrix and cell surface receptors, and may also be responsible for the repair of the tunic. The results obtained are consistent with experimental data on p48. The domain organization of protein suggests that p48 is an enzyme involved in the tunic tunning and is an important regulator of the organization of the extracellular matrix.

Keywords: ascidian, p48, thrombospondin, tyrosinase, tunic, tunning

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Authors: Karthyayani Rajamani, Yi-Chun Lin, Tung-Chou Wen, Jeanne Hsieh, Yi-Maun Subeq, Jen-Wei Liu, Po-Cheng Lin, Horng-Jyh Harn, Shinn-Zong Lin, Tzyy-Wen Chiou

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Assuring cell quality is an essential parameter for the success of stem cell therapy, utilization of various components to improve this potential has been the primary goal of stem cell research. The aim of this study was not only to demonstrate the capacity of trans-cinnamaldehyde (TC) to reverse stress-induced senescence but also improve the therapeutic abilities of stem cells. Because of the availability and the promising application potential in regenerative medicine, adipose-derived stem cells (ADSCs) were chosen for the study. We found that H2O2 treatment resulted in the expression of senescence characteristics in the ADSCs, including decreased proliferation rate, increased senescence-associated- β-galactosidase (SA-β-gal) activity, decreased SIRT1 (silent mating type information regulation 2 homologs) expression and decreased telomerase activity. However, TC treatment was sufficient to rescue or reduce the effects of H2O2 induction, ultimately leading to an increased proliferation rate, a decrease in the percentage of SA-β-gal positive cells, upregulation of SIRT1 expression, and increased telomerase activity of the senescent ADSCs at the cellular level. Further recently it was observed that the ADSCs were treated with TC without induction of senescence, all the before said positives were observed. Moreover, a chemically induced liver fibrosis animal model was used to evaluate the functionality of these rescued cells in vivo. Liver dysfunction was established by injecting 200 mg/kg thioacetamide (TAA) intraperitoneally into Wistar rats every third day for 60 days. The experimental rats were separated into groups; normal group (rats without TAA induction), sham group (without ADSC transplantation), positive control group (transplanted with normal ADSCs); H2O2 group (transplanted with H2O2 -induced senescent ADSCs), H2O2+TC group (transplanted with ADSCs pretreated with H2O2 and then further treated with TC) and TC group (ADSC treated with TC without H2O2 treatment). In the transplantation group, 1 × 106 human ADSCs were introduced into each rat via direct liver injection. Based on the biochemical analysis and immunohistochemical staining results, it was determined that the therapeutic effects on liver fibrosis by the induced senescent ADSCs (H2O2 group) were not as significant as those exerted by the normal ADSCs (the positive control group). However, the H2O2+TC group showed significant reversal of liver damage when compared to the H2O2 group 1 week post-transplantation. Further ADSCs without H2O2 treatment but with just TC treatment performed much better than all the groups. These data confirmed that the TC treatment had the potential to improve the therapeutic effect of ADSCs. It is therefore suggested that TC has potential applications in maintaining stem cell quality and could possibly aid in the treatment of senescence-related disorders.

Keywords: senescence, SIRT1, adipose derived stem cells, liver fibrosis

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Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe

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Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.

Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline

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Authors: Taha Kadir Yesin, Hanyu Liu, Zhangfan Ding, Amit Singh, Qi Tian, Yuheng Zhang, Biswajyoti Borah, Junyu Chen, Anjali P. Kusumbe

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The skeletal structure and bone marrow endothelium collectively form a critical functional unit essential for bone development, health, and aging. At the core of osteogenesis and bone formation lies the dynamic process of angiogenesis. In this study, we reveal a potent endogenous anabolic NCAM1-14.3.3. ζδ-derived- Peptide interaction, which stimulates bone angiogenesis and osteogenesis during homeostasis, aging, and age-related bone diseases. Employing high-resolution imaging and inducible cell-specific mouse genetics, our results elucidate the pivotal role of the NCAM1-14.3.3.ζδ-derived-Peptide interaction in driving the expansion of Clec14a+ angiogenic endothelial cells. Notably, Clec14a+ endothelial cells express key osteogenic factors. The NCAM1-14.3.3.ζδ-derived-Peptide interaction in osteoblasts drives osteoblast differentiation, ultimately contributing to the genesis of bone. Moreover, the NCAM1-14.3.3.ζδ-derived-Peptide interaction leads to a reduction in bone resorption. In age-associated vascular and bone loss diseases, stimulating the NCAM1-14.3.3.ζδ-derived-Peptide interaction not only promotes angiogenesis but also reverses bone loss. Consequently, harnessing the endogenous anabolic potential of the NCAM1-14.3.3.ζδ-derived-Peptide interaction emerges as a promising therapeutic modality for managing age-related bone diseases.

Keywords: endothelial cell, NCAM1, Clec14a, 14.3.3.ζδ

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Authors: Emanuela Chiarella, Clelia Nisticò, Nicola Lombardo, Giovanna Lucia Piazzetta, Nadia Lobello, Maria Mesuraca

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Killian’s Antrochoanal Polyp is a benign lesion of the maxillary sinus characterized by unilateral nasal obstruction, pus discharge, and headache. It affects, more commonly children and young adults. Although its etiology still remains unclear, chronic inflammation, autoreactivity, allergies, and viral infections are strongly associated with its formation and development, resulting in nasal tissue remodeling. We aimed to investigate the stem cells components which reside in this pathological tissue. In particular, we adopted a protocol for the isolation and culturing of mesenchymal stem cells from surgical biopsies of three Killian nasal polyp patients (KNP-MSCs) as well as from their healthy nasal tissue (HNT-MSCs) that were used as controls. The immunophenotype profile of HNT-MSCs and KNP-MSCs was more similar, with a marked positivity for CD73, CD90, and CD105 expression, while being negative for CD34 and CD14 haematopoietic genes. Cell proliferation assay showed that KNP-MSCs had a replicative disadvantage compared to HNT-MSCs, as evidenced by the significantly lower number of cells in the S-phase of the cell cycle. KNP-MSCs also took longer to close a wound than HNT-MSCs, indicating a partial epithelial phenotype in which low levels of ICAM-1 mRNA and a significant increase in E-CAD transcript were detectable. Subsequently, the differentiation potential of both MSCs populations was analyzed by inducing osteoblastic or adipocyte differentiation for up to 20 days. KNP-MSCs showed the ability to differentiate into osteoblasts, although ALP activity as well as the number and size of calcium deposits were lower than osteogenic induced-HNT-MSCs. Also, mRNA levels of osteoblastic marker genes (OCN, OPN, OSX, RUNX2) resulted lower compared to control cell population. Instead, the analysis of the adipogenic differentiation potential showed a similar behavior between KNP-MSCs and HNT-MSCs considering that the amount of lipid droplets, the expression of adipocyte-specific genes (FABP4, AdipoQ, PPARγ2, LPL) and the content of triacylglycerols were almost overlapping. Taken together, these results first demonstrated that Killian's nasal polyp is a source of mesenchymal stem cells with self-renewal and multi-differentiative capabilities.

Keywords: Mesenchymal stem cells, adipogenic differentiation, osteogenic differentiation, EMT

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Authors: Shwu-Ling Peng, Chiung-Man Tsai, Chia-Jui Weng

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Chronic micro-inflammation is a hallmark of many aging-related neurodegenerative and metabolic syndrome-driven diseases. In high glucose (HG) environment, reactive oxygen species (ROS) is generated and the ROS induced inflammation, cytokines secretion, DNA damage, and cell cycle arrest to lead to cellular senescence. Water chestnut shell (WCS) is a plant hull which containing polyphenolic compounds and showed antioxidant and anticancer activities. Orchid, which containing a natural polysaccharide compound, possesses many physiological activities including anti-inflammatory and neuroprotective effects. These agricultural plants might be able to reduce oxidative stress and inflammation. This study was used HG-induced human normal dermal fibroblasts (HG-HNDFs) as an in vitro model to disclose the effects of water extract of Phalaenopsis orchid flower (WEPF) and ethanol extract of water chestnut shell (EEWCS) on the anti-aging and their underlying molecular mechanisms. The toxicity of extracts on human normal dermal fibroblasts (HNDFs) was determined by MTT method. The senescence of cells was assayed by β-galactosidase (SA-β-gal) kit. ROS and nitrate production was analyzed by Intracellular ROS contents and ELISA, respectively. Western blotting was used to detect the proteins in cells. The results showed that the exposure of HNDFs to HG (30 mM) for 72 h were caused cellular senescence and arrested cells at G0/G1 phase. Indeed, the treatment of HG-HNDFs with WEPF (200 μg/ml) and EEWCS (10 μg/ml) significantly released cell cycle arrest and promoted cell proliferation. The G1/S phase transition regulatory proteins such as protein retinoblastoma (pRb), p53, and p16ᴵᴺᴷ⁴ᵃ depressed by WEPF and EEWCS were also observed. Additionally, the treatment of WEPF and EEWCS increased the activity of HO-1 through upregulating Nrf2 as well as decreased the ROS and NO of HG-HNDFs. Therefore, the senescence marker protein-30 (SMP30) in cells was diminished. In conclusion, the WEPF and EEWCS might inhibit HG-induced aging of HNDFs by reducing oxidative stress and free radicals.

Keywords: agricultural plant extract, anti-aging, high glucose, Phalaenopsis orchid flower, water chestnut shell

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Authors: Zeynep Busra Velioglu, Deniz Pulat, Beril Demirbakan, Burak Ozcan, Ece Bayrak, Cevat Erisken

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Bone tissue has the ability to perform a wide array of functions including providing posture, load-bearing capacity, protection for the internal organs, initiating hematopoiesis, and maintaining the homeostasis of key electrolytes via calcium/phosphate ion storage. The most common cause for bone defects is extensive trauma and subsequent infection. Bone tissue has the self-healing capability without a scar tissue formation for the majority of the injuries. However, some may result with delayed union or fracture non-union. Such cases include reconstruction of large bone defects or cases of compromised regenerative process as a result of avascular necrosis and osteoporosis. Several surgical methods exist to treat bone defects, including Ilizarov method, Masquelete technique, growth factor stimulation, and bone replacement. Unfortunately, these are technically demanding and come with noteworthy disadvantages such as lengthy treatment duration, adverse effects on the patient’s psychology, repeated surgical procedures, and often long hospitalization times. These limitations associated with surgical techniques make bone substitutes an attractive alternative. Here, it was hypothesized that a 3D printed scaffold will mimic trabecular bone in terms of biomechanical properties and that such scaffolds will support cell attachment and survival. To test this hypothesis, this study aimed at fabricating poly(lactic acid), PLA, structures using 3D printing technology for trabecular bone defects, characterizing the scaffolds and comparing with bovine trabecular bone. Capacity of scaffolds on human bone marrow stem cell (hBMSC) attachment and survival was also evaluated. Cubes with a volume of 1 cm³ having pore sizes of 0.50, 1.00 and 1.25 mm were printed. The scaffolds/grafts were characterized in terms of porosity, contact angle, compressive mechanical properties as well cell response. Porosities of the 3D printed scaffolds were calculated based on apparent densities. For contact angles, 50 µl distilled water was dropped over the surface of scaffolds, and contact angles were measured using ‘Image J’ software. Mechanical characterization under compression was performed on scaffolds and native trabecular bone (bovine, 15 months) specimens using a universal testing machine at a rate of 0.5mm/min. hBMSCs were seeded onto the 3D printed scaffolds. After 3 days of incubation with fully supplemented Dulbecco’s modified Eagle’s medium, the cells were fixed using 2% formaldehyde and glutaraldehyde mixture. The specimens were then imaged under scanning electron microscopy. Cell proliferation was determined by using EZQuant dsDNA Quantitation kit. Fluorescence was measured using microplate reader Spectramax M2 at the excitation and emission wavelengths of 485nm and 535nm, respectively. Findings suggested that porosity of scaffolds with pore dimensions of 0.5mm, 1.0mm and 1.25mm were not affected by pore size, while contact angle and compressive modulus decreased with increasing pore size. Biomechanical characterization of trabecular bone yielded higher modulus values as compared to scaffolds with all pore sizes studied. Cells attached and survived in all surfaces, demonstrating higher proliferation on scaffolds with 1.25mm pores as compared with those of 1mm. Collectively, given lower mechanical properties of scaffolds as compared to native bone, and biocompatibility of the scaffolds, the 3D printed PLA scaffolds of this study appear as candidate substitutes for bone repair and regeneration.

Keywords: 3D printing, biomechanics, bone repair, stem cell

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Authors: Somorjeet Sharma Shamurailatpam, Rabindra Das, A. Suchitra Devi

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Computer and video display users might complain about Asthenopia, burning, dry eyes etc. The management of dry eyes is often not in the lines of severity. Following systematic evaluation and grading, dry eye disease is one condition that can be practiced at all levels of ophthalmic care. In the present study, different spectrum causing dry eye and prevalence of dry eye disease in computer users of Manipur, India are determined with 600 individuals (300 cases and 300 control). Individuals between 15 and 50 years who used computers for more than 3 hrs a day for 1 year or more were included. Tear break up time (TBUT) and Schirmer’s test were conducted. It shows that 33 (20.4%) out of 164 males and 47 (30.3%) out of 136 females have dry eye. Possible explanation for the observed result is discussed.

Keywords: asthenopia, computer vision syndrome, dry eyes, Schirmer's test, TBUT

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Authors: Richard Joseph, Nerey Mvungi

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An electric power system includes a generating, a transmission, a distribution and consumers subsystems. An electrical power network in Tanzania keeps growing larger by the day and become more complex so that, most utilities have long wished for real-time monitoring and remote control of electrical power system elements such as substations, intelligent devices, power lines, capacitor banks, feeder switches, fault analyzers and other physical facilities. In this paper, the concept of automation of management of power systems from generation level to end user levels was determined by using Power System Simulator for Engineering (PSS/E) version 30.3.2.

Keywords: automation, distribution subsystem, generating subsystem, PSS/E, TANESCO, transmission subsystem

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Authors: Ji Jiazheng, Wang Jingrao, Jin Xin, Zhang Hong

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Diabetes mellitus is a metabolic disease characterized by high blood sugar. A long-standing hyperglycemic state can lead to various tissue damage. Diabetic retinopathy is the most common and widely studied ocular complication and has become the leading cause of blindness in my country. At the same time, diabetes has profound clinically relevant effects on the cornea, leading to keratopathy and vision-threatening. The cornea is an avascular tissue and is sensitive to hyperglycemia, Keratopathy caused by diabetes is usually chronic, they are called diabetic keratopathy or diabetic neurotrophic keratopathy, leading to several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity. Corneal stem cell dysfunction in diabetic patients as an important influencing factor of diabetic keratopathy. The consequences of this condition are often underestimated. The limbus is located between the cornea and the sclera tissue. The limbal stroma consists of a series of radial elevations with fibrovascular centers known as palisades of Vogt (POV). Previous studies have shown that palisades of Vogt (POV), as the main site of limbal stem cells, plays an important role in the homeostasis of the corneal epithelium. Therefore, POV plays a vital role in the healing of corneal epithelial surgery and postoperative evaluation. IVCM can observe the condition of the corneal epithelium at the cellular level. It has profound significance and guidance for the evaluation of limbal and limbal stem cells. We have previously observed structural changes in POV in HSK and HZO patients on IVCM. At present, there have been reports involving limbal stem cell dysfunction in diabetic patients, but the specific pathogenesis is still unclear. However, there are no studies on POV morphological changes in patients with DM. Therefore, we performed statistics and compared the correlation between POV morphological changes and corneal epithelial basal cell density, corneal nerves, and length of disease in DM patients and normal humans using IVCM studies. At the same time, fundoscopy was used to observe the correlation between the thickness of RNFL and the thickness of GCC and POV in diabetic patients. And to observe the correlation between SVD, DVD and POV for research.

Keywords: confocal microscopy, fundus, limbal stem cells, diabetes

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Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

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The elaboration of effective drug delivery vehicles is still topical nowadays since targeted drug delivery is one of the most important challenges of the modern nanomedicine. The last decade has witnessed enormous research focused on synthetic cationic polymers (CPs) due to their flexible properties, in particular as non-viral gene delivery systems, facile synthesis, robustness, not oncogenic and proven gene delivery efficiency. However, the toxicity is still an obstacle to the application in pharmacotherapy. For overcoming the problem, creation of new cationic compounds including the polymeric nano-size particles – nano-containers (NCs) loading with different pharmaceuticals and biologicals is still relevant. In this regard, a variety of NCs-based drug delivery systems have been developed. We have found that amino acid-based biodegradable polymers called as pseudo-proteins (PPs), which can be cleared from the body after the fulfillment of their function are highly suitable for designing pharmaceutical NCs. Among them, one of the most promising are NCs made of biodegradable Cationic PPs (CPPs). For preparing new cationic NCs (CNCs), we used CPPs composed of positively charged amino acid L-arginine (R). The CNCs were fabricated by two approaches using: (1) R-based homo-CPPs; (2) Blends of R-based CPPs with regular (neutral) PPs. According to the first approach NCs we prepared from CPPs 8R3 (composed of R, sebacic acid and 1,3-propanediol) and 8R6 (composed of R, sebacic acid and 1,6-hexanediol). The NCs prepared from these CPPs were 72-101 nm in size with zeta potential within +30 ÷ +35 mV at a concentration 6 mg/mL. According to the second approach, CPPs 8R6 was blended in organic phase with neutral PPs 8L6 (composed of leucine, sebacic acid and 1,6-hexanediol). The NCs prepared from the blends were 130-140 nm in size with zeta potential within +20 ÷ +28 mV depending on 8R6/8L6 ratio. The stability studies of fabricated NCs showed that no substantial change of the particle size and distribution and no big particles’ formation is observed after three months storage. In vitro biocompatibility study of the obtained NPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed both type cathionic NCs are biocompatible. The obtained data allow concluding that the obtained CNCs are promising for the application as biodegradable drug delivery vehicles. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 'New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications'.

Keywords: biodegradable polymers, cationic pseudo-proteins, nano-containers, drug delivery vehicles

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Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

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Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.

Keywords: kynurenine metabolites, neurotoxicity, quinolinic acid, SH-SY5Y neuroblastoma

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Authors: N. Slepickova Kasalkova, P. Slepicka, L. Bacakova, V. Svorcik

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Tissue engineering includes combination of materials and techniques used for the improvement, repair or replacement of the tissue. Scaffolds, permanent or temporally material, are used as support for the creation of the "new cell structures". For this important component (scaffold), a variety of materials can be used. The advantage of some polymeric materials is their cytocompatibility and possibility of biodegradation. Poly(L-lactic acid) (PLLA) is a biodegradable,  semi-crystalline thermoplastic polymer. PLLA can be fully degraded into H₂O and CO₂. In this experiment, the effect of the surface modification of biodegradable polymer (performed by plasma treatment) on the various cell types was studied. The surface parameters and changes of the physicochemical properties of modified PLLA substrates were studied by different methods. Surface wettability was determined by goniometry, surface morphology and roughness study were performed with atomic force microscopy and chemical composition was determined using photoelectron spectroscopy. The physicochemical properties were studied in relation to cytocompatibility of human osteoblast (MG 63 cells), rat vascular smooth muscle cells (VSMC), and human stem cells (ASC) of the adipose tissue in vitro. A fluorescence microscopy was chosen to study and compare cell-material interaction. Important parameters of the cytocompatibility like adhesion, proliferation, viability, shape, spreading of the cells were evaluated. It was found that the modification leads to the change of the surface wettability depending on the time of modification. Short time of exposition (10-120 s) can reduce the wettability of the aged samples, exposition longer than 150 s causes to increase of contact angle of the aged PLLA. The surface morphology is significantly influenced by duration of modification, too. The plasma treatment involves the formation of the crystallites, whose number increases with increasing time of modification. On the basis of physicochemical properties evaluation, the cells were cultivated on the selected samples. Cell-material interactions are strongly affected by material chemical structure and surface morphology. It was proved that the plasma treatment of PLLA has a positive effect on the adhesion, spreading, homogeneity of distribution and viability of all cultivated cells. This effect was even more apparent for the VSMCs and ASCs which homogeneously covered almost the whole surface of the substrate after 7 days of cultivation. The viability of these cells was high (more than 98% for VSMCs, 89-96% for ASCs). This experiment is one part of the basic research, which aims to easily create scaffolds for tissue engineering with subsequent use of stem cells and their subsequent "reorientation" towards the bone cells or smooth muscle cells.

Keywords: poly(L-lactic acid), plasma treatment, surface characterization, cytocompatibility, human osteoblast, rat vascular smooth muscle cells, human stem cells

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Authors: Shivani Khare

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It is of paramount concern for economists to uncover the factors that determine human capital development, considered now to be one of the major factors behind economic growth and development. However, no human action is isolated but rather works within the set-up of the society. In recent years, a new field of investigation has come up that analyses the relationships that exist between social and human capital. Along these lines, this paper explores the effect of social capital on the indicators of human capital development – life expectancy at birth, mean years of schooling, and per capita income. The applied part of the analysis is performed using a panel data model for OECD countries and by using a series of chronological periods that within the 2005–2020 time frame.

Keywords: social capital, human capital development, trust, social networks, socioeconomics

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Authors: Yufan Mu

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High salinity process water (HSPW) is often applied in copper ore flotation to alleviate freshwater shortage; however, it is detrimental to copper flotation as it strongly enhances copper activation of pyrite. In this study, the depression effect of a strong oxidiser, potassium ferrate (𝐾₂𝐹₄), on the flotation of copper-activated pyrite was tested to realise the selective separation of pyrite from copper minerals (e.g., chalcopyrite) in flotation using HSPW. The flotation results show that when (𝐾₂𝐹₄) was added in the flotation cell during conditioning, (𝐾₂𝐹₄) could selectively depress copper-activated pyrite while improving chalcopyrite flotation. The depression mechanism of (𝐾₂𝐹₄) on pyrite was ascribed to the significant increase in the pulp potential (Eₕ), dissolved oxygen (DO) concentration and the amount of ferric oxyhydroxides as a result of ferrate decomposition. In the flotation cell, the high Eh and DO concentration promoted the oxidation of low valency metal species (𝐶⁺𝐹e²⁺) released from mineral surfaces and forged steel grinding media, and the resultant high valency metal oxyhydroxides 𝐶u(𝑂H)₂⁄Fe(OH)₃ together with the ferric oxyhydroxides from ferrate decomposition preferentially precipitated on pyrite surface due to its more cathodic nature compared with chalcopyrite, which increased pyrite surface hydrophilicity and reduced its floatability. This study reveals that (𝐾₂𝐹₄) is a highly efficient depressant for pyrite when separating copper minerals from pyrite in flotation using HSPW if dosed properly.

Keywords: copper flotation, pyrite depression, copper-activated pyrite, potassium ferrate, high salinity process water

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Authors: Ching-Yi Yiu, Hui-Chen Hsu

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Objectives: Head and neck cancer (HNC) is a big global health problem in the world. Despite the development of diagnosis and treatment, the overall survival of HNC is still low. The well recognition of the interaction of the host immune system and cancer cells has led to realizing the processes of tumor initiation, progression and metastasis. Many systemic inflammatory responses have been shown to play a crucial role in cancer progression. The pre and post-treatment nutritional and immunological status of HNC patients is a reliable prognostic indicator of tumor outcomes and survivors. Methods: Between July 2020 to June 2022, We have enrolled 60 HNC patients, including 59 males and 1 female, in Chi Mei Medical Center, Liouying, Taiwan. The age distribution was from 37 to 81 years old (y/o), with a mean age of 57.6 y/o. We evaluated the pre-and post-treatment nutritional and immunological status of these HNC patients with body weight, body weight loss, body mass index (BMI), whole blood count including hemoglobin (Hb), lymphocyte, neutrophil and platelet counts, biochemistry including prealbumin, albumin, c-reactive protein (CRP), with the time period of before treatment, post-treatment 3 and 6 months. We calculated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to assess how these biomarkers influence the outcomes of HNC patients. Results: We have carcinoma of the hypopharynx in 21 cases with 35％, carcinoma of the larynx in 9 cases, carcinoma of the tonsil and tongue every 6 cases, carcinoma soft palate and tongue base every 5 cases, carcinoma of buccal mucosa, retromolar trigone and mouth floor every 2 cases, carcinoma of the hard palate and low lip each 1 case. There were stage I 15 cases, stage II 13 cases, stage III 6 cases, stage IVA 10 cases, and stage IVB 16 cases. All patients have received surgery, chemoradiation therapy or combined therapy. We have wound infection in 6 cases, 2 cases of pharyngocutaneous fistula, flap necrosis in 2 cases, and mortality in 6 cases. In the wound infection group, the average BMI is 20.4 kg/m2; the average Hb is 12.9 g/dL, the average albumin is 3.5 g/dL, the average NLR is 6.78, and the average PLR is 243.5. In the PC fistula and flap necrosis group, the average BMI is 21.65 kg/m2; the average Hb is 11.7 g/dL, the average albumin is 3.15 g/dL, average NLR is 13.28, average PLR is 418.84. In the mortality group, the average BMI is 22.3 kg/m2; the average Hb is 13.58 g/dL, the average albumin is 3.77 g/dL, the average NLR is 6.06, and the average PLR is 275.5. Conclusion: HNC is a big challenging public health problem worldwide, especially in the high prevalence of betel nut consumption area Taiwan. Besides the definite risk factors of smoking, drinking and betel nut related, the other biomarkers may play significant prognosticators in the HNC outcomes. We concluded that the average BMI is less than 22 kg/m2, the average Hb is low than 12.0 g/dL, the average albumin is low than 3.3 g/dL, the average NLR is low than 3, and the average PLR is more than 170, the surgical complications and mortality will be increased, and the prognosis is poor in HNC patients.

Keywords: nutritional, immunological, neutrophil-to-lymphocyte ratio, paltelet-to-lymphocyte ratio.

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Authors: Fadilah Aleanizy

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Colicins are a family of bacterial toxins that kill Escherichia coli and other closely related species. The mode of action of colicins involves binding to an outer membrane receptor and translocation across the cell envelope, leading to cytotoxicity through specific targets. The mechanism of colicin cytotoxicity includes a non-specific endonuclease activity or depolarization of the cytoplasmic membrane by pore-forming activity. For Group A colicins, translocation requires an interaction between the N-terminal domain of the colicin and a series of membrane- bound and periplasmic proteins known as the Tol system (TolB, TolR, TolA, TolQ, and Pal and the active domain must be translocated through the outer membranes. Protein-protein interactions are intrinsic to virtually every cellular process. The transient protein-protein interactions of the colicin include the interaction with much more complicated assemblies during colicin translocation across the cellular membrane to its target. The potassium release assay detects variation in the K+ content of bacterial cells (K+in). This assays is used to measure the effect of pore-forming colicins such as ColA on an indicator organism by measuring the changes of the K+ concentration in the external medium (K+out ) that are caused by cell killing with a K+ selective electrode. One of the goals of this work is to employ a quantifiable in-vivo method to spot which Tol protein are more implicated in the interaction with colicin A as it is translocated to its target.

Keywords: K+ efflux, Colicin A, Tol-proteins, E. coli

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Authors: Tie-Qing Zhang, Seunghun Jung, Young-Bae Kim

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This research is devoted to developing a membrane reactor to flexibly meet the hydrogen demand of onboard fuel cells, which is an important part of green energy development. Among many renewable chemical products, dimethyl ether (DME) has the advantages of low reaction temperature (400 °C in this study), high hydrogen atom content, low toxicity, and easy preparation. Autothermal reforming, on the other hand, has a high hydrogen recovery rate and exhibits thermal neutrality during the reaction process, so the additional heat source in the hydrogen production process can be omitted. Therefore, the DME auto thermal reforming process was adopted in this study. To control the temperature of the reaction catalyst bed and hydrogen production rate, a Model Predictive Control (MPC) scheme was designed. Taking the above two variables as the control objectives, stable operation of the reformer can be achieved by controlling the flow rates of DME, steam, and high-purity air in real-time. To prevent catalyst poisoning in the fuel cell, the hydrogen needs to be purified to reduce the carbon monoxide content to below 50 ppm. Therefore, a Pd-Ag hydrogen semi-permeable membrane with a thickness of 3-5 μm was inserted into the auto thermal reactor, and the permeation efficiency of hydrogen was improved by steam purging on the permeation side. Finally, hydrogen with a purity of 99.99 was obtained.

Keywords: hydrogen production, auto thermal reforming, membrane, fuel cell

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