Search results for: cancer cell

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

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It has been reported that deer antler extract has bone-strengthening activity and effectively used in bone diseases therapy. However, little is known about the cellular and molecular mechanism of this effect. The upper section, mid section, and base of the antler has been known to exhibit different biological properties. Present study investigated the effects of these three parts of deer antler extracts on bone formation and resorption. The effects of deer antler extracts (DH) on bone formation were determined by cell proliferation, alkaline phosphatase (ALP) activity, collagen synthesis, and mineralization in human osteoblastic MG-63 cells. The effect on bone resorption was determined by osteoclastogenesis from bone marrow-derived precursor cells driven by RANKL. Ethanol extracts of DH (50 ~ 100 µg/ml) dose-dependently increased cell proliferation, and upper part increased the cell proliferation by 118.4% while mid and base parts increased proliferation by 107.8% and 102.3%, respectively. ALP activity was significantly increased by upper part of the DH treatment. After enhancement of ALP activity, significant augmentation of collagen synthesis and calcification assessed by Sirus red and Alzarin red staining, respectively, was observed in upper part of the DH treatment. The effect of DH on bone resorption was not observed in all three parts of the DH. These results could provide a mechanistic explanation for the bone-strengthening effects of DH.

Keywords: alkaline phosphatase, collagen synthesis, deer antler, osteoblastic MG-63 cells

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Authors: Sh. Foroughi, V. Karamzadeh, M. Packirisamy

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This paper presents design and analysis of an electrothermally symmetrical actuated microgripper applicable for performing micro assembly or biological cell manipulation. Integration of micro-optics with microdevice leads to achieve extremely precise control over the operation of the device. Geometry, material, actuation, control, accuracy in measurement and temperature distribution are important factors which have to be taken into account for designing the efficient microgripper device. In this work, analyses of four different geometries are performed by means of COMSOL Multiphysics 5.2 with implementing Finite Element Methods. Then, temperature distribution along the fingertip, displacement of gripper site as well as optical efficiency vs. displacement and electrical potential are illustrated. Results show in addition to the industrial application of this device, the usage of that as a cell manipulator is possible.

Keywords: electro thermal actuator, MEMS, microgripper, MOEMS

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Authors: Hanan Alsaeid Alshenawy

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Background: Cervical dysplasia, which is potentially precancerous, has increased in young women. Detection of cervical is important for reducing morbidity and mortality in cervical cancer. This study analyzes the immunohistochemical expression of p16, HPV L1 capsid protein and Ki67 in cervical intraepithelial lesions and correlates them with lesion grade to develop a set of markers for diagnosis and detect the prognosis of cervical cancer precursors. Methods: 75 specimens were analyzed including 15 cases CIN 1, 28 CIN 2, 20 CIN 3, and 12 cervical squamous carcinoma, besides 10 normal cervical tissues. They were stained for p16, HPV L1 and Ki-67. Sensitivity, specificity, predictive values and accuracy were evaluated for each marker. Results: p16 expression increased during the progression from CIN 1 to carcinoma. HPV L1 positivity was detected in CIN 2 and decreased gradually as the CIN grade increased but disappear in carcinoma. Strong Ki-67 expression was observed with high grades CIN and carcinoma. p16, HPV L1 and Ki67 were sensitive but with variable specificity in detecting CIN lesions. Conclusions: p16, HPV L1 and Ki67 are useful set of markers in establishing the risk of high-grade CIN. They complete each other to reach accurate diagnosis and prognosis.

Keywords: p16, HPV L1, Ki67, CIN, cervical carcinoma

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Authors: M. Hosseinnejad, K. Gharanjig

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In the present study, metal free organic dyes were prepared and used as photo-sensitizers in dye-sensitized solar cells. Double rhodanine was utilized as the fundamental electron acceptor group to which electron donor aldehyde with varying substituents was attached to produce new organic dye. This dye was first purified and then characterized by analytical techniques. Spectrophotometric evaluations of the prepared dye in solution and on a nano anatase TiO₂ substrate were carried out in order to assess possible changes in the status of the dyes in different environments. The results show that the dye form j-type aggregates on the nano TiO₂. Additionally, oxidation potential measurements were also carried out. Finally, dye sensitized solar cell based on synthesized dye was fabricated in order to determine the photovoltaic behavior and conversion efficiency of individual dye.

Keywords: conversion efficiency, dye-sensitized solar cell, photovoltaic behavior, sensitizer

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Authors: Dahi Ghareab Abdelsalam Ibrahim, R. H. Bakr

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Ionizing radiation, such as gamma radiation and X-rays, has many applications in medical diagnoses and cancer treatment. In this paper, we used the windowed Fourier transform to extract the complex image of the deformed red blood cells. The real values of the complex image are used to extract the best fitting of the deformed cell boundary. Male albino rats are irradiated by γ-rays from ⁶⁰Co. The male albino rats are anesthetized with ether, and then blood samples are collected from the eye vein by heparinized capillary tubes for studying the radiation-damaging effect in-vivo by the proposed windowed Fourier transform. The peripheral blood films are prepared according to the Brown method. The peripheral blood film is photographed by using an Automatic Image Contour Analysis system (SAMICA) from ELBEK-Bildanalyse GmbH, Siegen, Germany. The SAMICA system is provided with an electronic camera connected to a computer through a built-in interface card, and the image can be magnified up to 1200 times and displayed by the computer. The images of the peripheral blood films are then analyzed by the windowed Fourier transform method to extract the precise deformation from the best fitting. Based on accurate deformation evaluation of the red blood cells, diseases can be diagnosed in their primary stages.

Keywords: windowed Fourier transform, red blood cells, phase wrapping, Image processing

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Authors: B. Fazekas, I. Korolov, K. Kutasi

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Plasma medicine, which involves the use of gas discharge plasmas for medical applications is a rapidly growing research field. The use of non-thermal atmospheric pressure plasmas in dermatology to assist tissue regeneration by improving the healing of infected and/or chronic wounds is a promising application. It is believed that plasma can activate cells, which are involved in the wound closure. Non-thermal atmospheric plasmas are rich in chemically active species (such as O and N-atoms, O2(a) molecules) and radiative species such as the NO, N2+ and N2 excited molecules, which dominantly radiate in the 200-500 nm spectral range. In order to understand the effect of plasma species, both of chemically active and radiative species on wound healing process, the interaction of physical plasma with the human skin cells is necessary. In order to clarify the effect of plasma radiation on the wound healing process we treated keratinocyte cells – that are one of the main cell types in human skin epidermis – covered with a layer of phosphate-buffered saline (PBS) with a low power atmospheric pressure plasma. For the generation of such plasma we have applied a plasma needle. Here, the plasma is ignited at the tip of the needle in flowing helium gas in contact with the ambient air. To study the effect of plasma radiation we used a plasma needle configuration, where the plasma species – chemically active radicals and charged species – could not reach the treated cells, but only the radiation. For the comparison purposes, we also irradiated the cells using a UV-B light source (FS20 lamp) with a 20 and 40 mJ cm-2 dose of 312 nm. After treatment the viability and the proliferation of the cells have been examined. The proliferation of cells has been studied with a real time monitoring system called Xcelligence. The results have indicated, that the 20 mJ cm-2 dose did not affect cell viability, whereas the 40 mJ cm-2 dose resulted a decrease in cell viability. The results have shown that the plasma radiation have no quantifiable effect on the cell proliferation as compared to the non-treated cells.

Keywords: UV radiation, non-equilibrium gas discharges (non-thermal plasmas), plasma emission, keratinocyte cells

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Authors: M. Chaichanyut, S. Tungjitkusolmun

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This paper is concerned with microwave (MW) ablation for a liver cancer tissue by using helix antenna. The antenna structure supports the propagation of microwave energy at 2.45 GHz. A 1½ turn spiral catheter-based microwave antenna applicator has been developed. We utilize the three-dimensional finite element method (3D FEM) simulation to analyze where the tissue heat flux, lesion pattern and volume destruction during MW ablation. The configurations of helix antenna where Helix air-core antenna and Helix Dielectric-core antenna. The 3D FEMs solutions were based on Maxwell and bio-heat equations. The simulation protocol was power control (10 W, 300s). Our simulation result, both helix antennas have heat flux occurred around the helix antenna and that can be induced the temperature distribution similar (teardrop). The region where the temperature exceeds 50°C the microwave ablation was successful (i.e. complete destruction). The Helix air-core antenna and Helix Dielectric-core antenna, ablation zone or axial ratios (Widest/length) were respectively 0.82 and 0.85; the complete destructions were respectively 4.18 cm³ and 5.64 cm³.

Keywords: liver cancer, Helix antenna, finite element, microwave ablation

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Authors: Chinedu Peter, Dashrath Singh

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Membrane computing is a computability model which abstracts its structures and functions from the biological cell. The main ingredient of membrane computing is the notion of a membrane structure, which consists of several cell-like membranes recurrently placed inside a unique skin membrane. The emergence of several variants of membrane computing gives rise to the notion of a P system. The paper presents a variant of P systems for arithmetic operations on non-negative integers based on the weak priorities for rule application. Consequently, we obtain deterministic P systems. Two membranes suffice. There are at most four objects for multiplication and five objects for division throughout the computation processes. The model is simple and has a potential for possible extension to non-negative integers and real numbers in general.

Keywords: P system, binary operation, determinism, weak rule priority

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Authors: Shen Jian, Hu Jie, Ma Jin, Peng Ying Hong, Fang Yi, Liu Wen Hai

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Biologically inspired design inspires inventions and new technologies in the field of engineering by mimicking functions, principles, and structures in the biological domain. To deal with the obstacles of cross-domain knowledge acquisition in the existing biologically inspired design process, functional semantic clustering based on functional feature semantic correlation and environmental constraint clustering composition based on environmental characteristic constraining adaptability are proposed. A knowledge cell clustering algorithm and the corresponding prototype system is developed. Finally, the effectiveness of the method is verified by the visual prosthetic device design.

Keywords: knowledge clustering, knowledge acquisition, knowledge based engineering, knowledge cell, biologically inspired design

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Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: Hyun-jin Kim, Gumgyung Gu, Dae-Hyun Ko, Woochang Lee, Sail Chun, Won-Ki Min

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Background: Ovarian carcinoma is the fourth most common cause of cancer-related death in women worldwide. HE4, a novel marker for ovarian cancer could be used for monitoring recurrence or progression of disease in patients with invasive epithelial ovarian carcinoma. It is further intended to be used in conjunction with CA 125 to estimate the risk of epithelial ovarian cancer in women presenting with an adnexal mass. In this study, we aim to evaluate the analytical performance and clinical utility of HE4 assay using Architect i 2000SR(Abbott Diagnostics, USA). Methods: The precision was evaluated according to Clinical and Laboratory Standards Institute(CLSI) EP5 guideline. Three levels of control materials were analyzed twice a day in duplicate manner over 20 days. We calculated within run and total coefficient of variation (CV) at each level of control materials. The linearity was evaluated based on CLSI EP6 guideline. Five levels of calibrator were prepared by mixing high and low level of calibrators. For 43 women with adnexal masses, HE4 and CA 125 were measured and Risk of ovarian malignancy (ROMA) scores were calculated. The patients’ medical records were reviewed to determine the clinical utility of HE4 and ROMA score. Results: In a precision study, the within-run and total CV were 2.0 % and 2.3% for low level of control material, 1.9% and 2.4% for medium level and 0.5 % and 1.1% for high level, respectively. The linear range of HE4 was 14.63 to 1475.15pmol/L. Of the 43 patients, two patients in pre-menopausal group showed the ROMA score above the cut-off level (7.3%). One of them showed CA 125 level within the reference range, while the HE4 was higher than the cut-off. Conclusion: The overall analytical performance of HE4 assay using Architect showed high precision and good linearity within clinically important range. HE4 could be an useful marker for managing patients with adnexal masses.

Keywords: HE4, CA125, ROMA, evaluation, performance

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Authors: Felipa De Mello-Sampayo

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Background: The aim of this study is to undertake, from a patient perspective, an economic analysis of presurgical teledermatology, comparing it with a conventional referral system. Store-and-forward teledermatology allows surgical planning, saving both time and number of visits involving travel, thereby reducing patients’ out-of-pocket expenses, i.e., costs that patients incur when traveling to and from health providers for treatment, visits’ fees, and the opportunity cost of time spent in visits. Method: Patients’ out-of-pocket expenses-effectiveness of presurgical teledermatology were analyzed in the setting of a public hospital during two years. The mean delay in surgery was used to measure effectiveness. The teledermatology network covering the area served by the Hospital Garcia da Horta (HGO), Portugal, linked the primary care centers of 24 health districts with the hospital’s dermatology department. The patients’ opportunity cost of visits, travel costs, and visits’ fee of each presurgical modality (teledermatology and conventional referral), the cost ratio between the most and least expensive alternative, and the incremental cost-effectiveness ratio were calculated from initial primary care visit until surgical intervention. Two groups of patients: those with squamous cell carcinoma and those with basal cell carcinoma were distinguished in order to compare the effectiveness according to the dermatoses. Results: From a patient perspective, the conventional system was 2.15 times more expensive than presurgical teledermatology. Teledermatology had an incremental out-of-pocket expenses-effectiveness ratio of €1.22 per patient and per day of delay avoided. This saving was greater in patients with squamous cell carcinoma than in patients with basal cell carcinoma. Conclusion: From a patient economic perspective, teledermatology used for presurgical planning and preparation is the dominant strategy in terms of out-of-pocket expenses-effectiveness than the conventional referral system, especially for patients with severe dermatoses.

Keywords: economic analysis, out-of-pocket expenses, opportunity cost, teledermatology, waiting time

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Authors: Rojith K. Balakrishnan

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Plasmablastic lymphoma (PBL) is an uncommon, recently described B-cell derived lymphoma that is most commonly seen in patients with Human Immunodeficiency Virus (HIV) infection. Here we report a case of PBL in a 35 year old man with HIV who presented with multiple subcutaneous swellings all over the body and oral mucosal lesions.The biopsy report was suggestive of Diffuse Large B Cell Lymphoma. Immunohistochemistry was done which showed, lymphoma cells, positive for MUM1, CD 138, and VS 38. The proliferation index (MIB) was 95%. Final report was consistent with the diagnosis of Plasmablastic Lymphoma. The lesion completely regressed after treatment with systemic chemotherapy. Up to date, only a few cases of plasmablastic lymphoma have been reported from India. Increased frequency of this lymphoma in HIV patients and rarity of the tumour, along with rapid response of the same to chemotherapy, make this case a unique one. Hence the knowledge about this new entity is important for clinicians who deal with HIV patients.

Keywords: human immunodeficiency virus (HIV), oral cavity lesion, plasmablastic lymphoma, subcutaneous swelling

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Authors: Yuriko Takayama, Norihiro Kato

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Quorum sensing (QS) is a cell-to-cell communication system in bacteria to regulate expression of target genes. In gram-negative bacteria, activation on QS is controlled by a concentration increase of N-acylhomoserine lactone (AHL), which can diffuse in and out of the cell. Effective control of QS is expected to avoid virulence factor production in infectious pathogens, biofilm formation, and antibiotic production because various cell functions in gram-negative bacteria are controlled by AHL-mediated QS. In this research, we applied cyclodextrins (CDs) as artificial hosts for the AHL signal to reduce the AHL concentration in the culture broth below its threshold for QS activation. The AHL-receptor complex induced under the high AHL concentration activates transcription of the QS-target gene. Accordingly, artificial reduction of the AHL concentration is one of the effective strategies to inhibit the QS. A hydrophobic cavity of the CD can interact with the acyl-chain of the AHL due to hydrophobic interaction in aqueous media. We studied N-hexanoylhomoserine lactone (C6HSL)-mediated QS in Serratia marcescens; accumulation of C6HSL is responsible for regulation of the expression of pig cluster. Inhibitory effects of added CDs on QS were demonstrated by determination of prodigiosin amount inside cells after reaching stationary phase, because production of prodigiosin depends on the C6HSL-mediated QS. By adding approximately 6 wt% hydroxypropyl-β-CD (HP-β-CD) in Luria-Bertani (LB) medium prior to inoculation of S. maecescens AS-1, the intracellularly accumulated prodigiosin was drastically reduced to 7-10%, which was determined after the extraction of prodigiosin in acidified ethanol. The AHL retention ability of HP-β-CD was also demonstrated by Chromobacterium violacuem CV026 bioassay. The CV026 strain is an AHL-synthase defective mutant that activates QS solely by adding AHLs from outside of cells. A purple pigment violacein is induced by activation of the AHL-mediated QS. We demonstrated that the violacein production was effectively suppressed when the C6HSL standard solution was spotted on a LB agar plate dispersing CV026 cells and HP-β-CD. Physico-chemical analysis was performed to study the affinity between the immobilized CD and added C6HSL using a quartz crystal microbalance (QCM) sensor. The COOH-terminated self-assembled monolayer was prepared on a gold electrode of 27-MHz AT-cut quartz crystal. Mono(6-deoxy-6-N, N-diethylamino)-β-CD was immobilized on the electrode using water-soluble carbodiimide. The C6HSL interaction with the β-CD cavity was studied by injecting the C6HSL solution to a cup-type sensor cell filled with buffer solution. A decrement of resonant frequency (ΔFs) clearly showed the effective C6HSL complexation with immobilized β-CD and its stability constant for MBP-SpnR-C6HSL complex was on the order of 102 M-1. The CD has high potential for engineered control of QS because it is safe for human use.

Keywords: acylhomoserine lactone, cyclodextrin, intracellular signaling, quorum sensing

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Authors: Edward Hage, Pieter Lietaert, Gabriel Abedrabbo

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Musculoskeletal disorders are an important category of work-related diseases. They are often caused by working in non-ergonomic postures and are preventable with proper workplace design, possibly including human-machine collaboration. This paper presents a methodology and a supporting software prototype to design a simple assembly cell with minimal ergonomic risk. The methodology helps to determine the optimal position and orientation of workpieces and workplace resources for specific operator assembly actions. The methodology is tested on an industrial use case: a collaborative robot (cobot) assisted assembly of a clamping device. It is shown that the automated methodology results in a workplace design with significantly reduced ergonomic risk to the operator compared to a manual design of the cell.

Keywords: ergonomics optimization, design for ergonomics, workplace design, pose generation

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Authors: Anamarija Kuhar, Veronika Kloboves Prevodnik, Nataša Nolde, Ulrika Klopčič

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The decision for immunocytochemistry (ICC) is usually made in the basis of the findings in Giemsa- and/or Papanicolaou- smears. More demanding diagnostic cases require preparation of additional cytological preparations. Therefore, it is convenient to suspend cytological samples in a liquid based medium (LBM) that preserve antigen and morphological properties. However, the duration of these properties being preserved in the medium is usually unknown. Eventually, cell morphology becomes impaired and altered, as well as antigen properties may be lost or become diffused. In this study, the influence of cytological sample storage length in in-house liquid based medium on antigen properties and cell morphology is evaluated. The question is how long the cytological samples in this medium can be stored so that the results of immunocytochemical reactions are still reliable and can be safely used in routine cytopathological diagnostics. The stability of 6 ICC markers that are most frequently used in everyday routine work were tested; Cytokeratin AE1/AE3, Calretinin, Epithelial specific antigen Ep-CAM (MOC-31), CD 45, Oestrogen receptor (ER), and Melanoma triple cocktail were tested on methanol fixed cytospins prepared from fresh fine needle aspiration biopsies, effusion samples, and disintegrated lymph nodes suspended in in-house cell medium. Cytospins were prepared on the day of the sampling as well as on the second, fourth, fifth, and eight day after sample collection. Next, they were fixed in methanol and immunocytochemically stained. Finally, the percentage of positive stained cells, reaction intensity, counterstaining, and cell morphology were assessed using two assessment methods: the internal assessment and the UK NEQAS ICC scheme assessment. Results show that the antigen properties for Cytokeratin AE1/AE3, MOC-31, CD 45, ER, and Melanoma triple cocktail were preserved even after 8 days of storage in in-house LBM, while the antigen properties for Calretinin remained unchanged only for 4 days. The key parameters for assessing detection of antigen are the proportion of cells with a positive reaction and intensity of staining. Well preserved cell morphology is highly important for reliable interpretation of ICC reaction. Therefore, it would be valuable to perform a similar analysis for other ICC markers to determine the duration in which the antigen and morphological properties are preserved in LBM.

Keywords: cytology samples, cytospins, immunocytochemistry, liquid-based cytology

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Authors: Débora P. Jaeschke, Eduardo A. Merlo, Rosane Rech, Giovana D. Mercali, Ligia D. F. Marczak

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Carotenoids are high value added pigments that can be alternatively extracted from some microalgae species. However, the application of carotenoids synthetized by microalgae is still limited due to the utilization of organic toxic solvents. In this context, studies involving alternative extraction methods have been conducted with more sustainable solvents to replace and reduce the solvent volume and the extraction time. The aim of the present work was to evaluate the extraction time of carotenoids from the microalgae Heterochlorella luteoviridis using moderate electric field (MEF) as a pre-treatment to the extraction. The extraction methodology consisted of a pre-treatment in the presence of MEF (180 V) and ethanol (25 %, v/v) for 10 min, followed by a diffusive step performed for 50 min using a higher ethanol concentration (75 %, v/v). The extraction experiments were conducted at 30 °C and, to keep the temperature at this value, it was used an extraction cell with a water jacket that was connected to a water bath. Also, to enable the evaluation of MEF effect on the extraction, control experiments were performed using the same cell and conditions without voltage application. During the extraction experiments, samples were withdrawn at 1, 5 and 10 min of the pre-treatment and at 1, 5, 30, 40 and 50 min of the diffusive step. Samples were, then, centrifuged and carotenoids analyses were performed in the supernatant. Furthermore, an exhaustive extraction with ethyl acetate and methanol was performed, and the carotenoids content found for this analyses was considered as the total carotenoids content of the microalgae. The results showed that the application of MEF as a pre-treatment to the extraction influenced the extraction yield and the extraction time during the diffusive step; after the MEF pre-treatment and 50 min of the diffusive step, it was possible to extract up to 60 % of the total carotenoids content. Also, results found for carotenoids concentration of the extracts withdrawn at 5 and 30 min of the diffusive step did not presented statistical difference, meaning that carotenoids diffusion occurs mainly in the very beginning of the extraction. On the other hand, the results for control experiments showed that carotenoids diffusion occurs mostly during 30 min of the diffusive step, which evidenced MEF effect on the extraction time. Moreover, carotenoids concentration on samples withdrawn during the pre-treatment (1, 5 and 10 min) were below the quantification limit of the analyses, indicating that the extraction occurred in the diffusive step, when ethanol (75 %, v/v) was added to the medium. It is possible that MEF promoted cell membrane permeabilization and, when ethanol (75 %) was added, carotenoids interacted with the solvent and the diffusion occurred easily. Based on the results, it is possible to infer that MEF promoted the decrease of carotenoids extraction time due to the increasing of the permeability of the cell membrane which facilitates the diffusion from the cell to the medium.

Keywords: moderate electric field (MEF), pigments, microalgae, ethanol

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Authors: Brian M. Mehling, Louis Quartararo, Marine Manvelyan, Paul Wang, Dong-Cheng Wu

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Numerous investigations suggest that Mesenchymal Stem Cells (MSCs) in general represent a valuable tool for therapy of symptoms related to chronic inflammatory diseases. Blue Horizon Stem Cell Therapy Program is a leading provider of adult and children’s stem cell therapies. Uniquely we have safely and efficiently treated more than 600 patients with documenting each procedure. The purpose of our study is primarily to monitor the immune response in order to validate the safety of intravenous infusion of human umbilical cord blood derived MSCs (UC-MSCs), and secondly, to evaluate effects on biomarkers associated with chronic inflammation. Nine patients were treated for conditions associated with chronic inflammation and for the purpose of anti-aging. They have been given one intravenous infusion of UC-MSCs. Our study of blood test markers of 9 patients with chronic inflammation before and within three months after MSCs treatment demonstrates that there is no significant changes and MSCs treatment was safe for the patients. Analysis of different indicators of chronic inflammation and aging included in initial, 24-hours, two weeks and three months protocols showed that stem cell treatment was safe for the patients; there were no adverse reactions. Moreover data from follow up protocols demonstrates significant improvement in energy level, hair, nails growth and skin conditions. Intravenously administered UC-MSCs were safe and effective in the improvement of symptoms related to chronic inflammation. Further close monitoring and inclusion of more patients are necessary to fully characterize the advantages of UC-MSCs application in treatment of symptoms related to chronic inflammation.

Keywords: chronic inflammatory diseases, intravenous infusion, stem cell therapy, umbilical cord blood derived mesenchymal stem cells (UC-MSCs)

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Authors: Pratthana Ammaraphitak, Piyachon Ketsuwan, Rattapoom Prommana

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Electricity production from vermicompost liquid was investigated in microbial fuel cells (MFCs). The aim of this study was to determine the performance of vermicompost liquid as a biocatalyst for electricity production by MFCs. Chemical and physical parameters of vermicompost liquid as total nitrogen, ammonia-nitrogen, nitrate, nitrite, total phosphorus, potassium, organic matter, C:N ratio, pH, and electrical conductivity in MFCs were studied. The performance of MFCs was operated in open circuit mode for 7 days. The maximum open circuit voltage (OCV) was 0.45 V. The maximum power density of 5.29 ± 0.75 W/m² corresponding to a current density of 0.024 2 ± 0.0017 A/m² was achieved by the 1000 Ω on day 2. Vermicompost liquid has efficiency to generate electricity from organic waste.

Keywords: vermicompost liquid, microbial fuel cell, nutrient, electricity production

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Authors: Haiyan Wang, Dongyun Wang, Yongyong Yan, Richard T. Jaspers, Gang Wu

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Mesenchymal stem cell and 3D printing-based bone tissue engineering present a promising technique to repair large-volume bone defects. Its success is highly dependent on cell attachment, spreading, osteogenic differentiation, and in vivo survival of stem cells on 3D-printed scaffolds. In this study, human salivary histatin-1 (Hst1) was utilized to enhance the interactions between human adipose-derived stem cells (hASCs) and 3D-printed β-tricalcium phosphate (β-TCP) bioceramic scaffolds. Fluorescent images showed that Hst1 significantly enhanced the adhesion of hASCs to both bioinert glass and 3D-printed β-TCP scaffold. In addition, Hst1 was associated with significantly higher proliferation and osteogenic differentiation of hASCs on 3D-printed β-TCP scaffolds. Moreover, coating 3D-printed β-TCP scaffolds with histatin significantly promotes the survival of hASCs in vivo. The ERK and p38 but not JNK signaling was found to be involved in the superior adhesion of hASCs to β-TCP scaffolds with the aid of Hst1. In conclusion, Hst1 could significantly promote the adhesion, spreading, osteogenic differentiation, and in vivo survival of hASCs on 3D-printed β-TCP scaffolds, bearing a promising application in stem cell/3D printing-based constructs for bone tissue engineering.

Keywords: 3d printing, adipose-derived stem cells, bone tissue engineering, histatin-1, osteogenesis

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Authors: Chakrit Thapphan, Suteeraporn Chaowattanapanit, Sorutsiri Chareonsudjai, Wisitsak Phoksawat, Supranee Phantanawiboon, Kiatichai Faksri, Steve W. Edwards, Kanin Salao

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Background: Psoriasis is a chronic inflammatory disease of the skin that is mediated by crosstalk between keratinocytes and immune cells, especially CD4+ T helper (Th) cells. To date, psoriasis is established as a T helper 17 (Th17) cell-mediated inflammatory process driven by the over-expression of Th17. However, the role of other CD4+T helper cells is rather controversial. Objective: Our study, thereby, aimed to characterize and analyze T cell subsets in the circulating blood of psoriasis patients and compare them to healthy controls. Methods: Peripheral blood mononuclear cells were isolated from the participants and stained with fluorescent dye-conjugated monoclonal antibodies specific for intracellular cytokines, including interferon-gamma (IFN- γ), interleukin (IL-4), IL-17 and forkhead box P3 (FOXP3), that can be used to define T helper 1 (Th1) cells, T helper 2 (Th2), T helper 17 (Th17) and regulatory T cells (Treg) respectively. Results: We found that the numbers of Th2 (59.6% ± 17.0) and Th17 (4.0% ± 2.0) cells in the circulating blood of psoriasis patients were significantly higher than those of the healthy controls (p= 0.0007 and 0.0013 respectively). In contrast, the numbers of Th1 and Treg cells were not significantly different between psoriasis patients and healthy controls (p= 0.0593 and 0.8518, respectively). Additionally, when adjusting these numbers of Th cells to Treg, we observed a similar trend that the ratio of Th2/Treg and Th17/Treg also elevated (p = 0.0007 and 0.0047, respectively). Conclusion: Taken together, our results suggest an imbalanced T exhibit toward the Th2 and Th17 skewed-immune responses in psoriasis patients.

Keywords: psoriasis, Th cell subsets, Th2 cells, Th17 cells, Treg cells

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Authors: Farideh Halakou, Emel Sen, Attila Gursoy, Ozlem Keskin

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Protein–Protein Interactions (PPIs) mediate major biological processes in living cells. The study of PPIs as networks and analyze the network properties contribute to the identification of genes and proteins associated with diseases. In this study, we have created the sub-networks of brain and lung metastasis from primary tumor in breast cancer. To do so, we used seed genes known to cause metastasis, and produced their interactions through a network-topology based prioritization method named GUILDify. In order to have the experimental support for the sub-networks, we further curated them using STRING database. We proceeded by modeling structures for the interactions lacking complex forms in Protein Data Bank (PDB). The functional enrichment analysis shows that KEGG pathways associated with the immune system and infectious diseases, particularly the chemokine signaling pathway, are important for lung metastasis. On the other hand, pathways related to genetic information processing are more involved in brain metastasis. The structural analyses of the sub-networks vividly demonstrated their difference in terms of using specific interfaces in lung and brain metastasis. Furthermore, the topological analysis identified genes such as RPL5, MMP2, CCR5 and DPP4, which are already known to be associated with lung or brain metastasis. Additionally, we found 6 and 9 putative genes that are specific for lung and brain metastasis, respectively. Our analysis suggests that variations in genes and pathways contributing to these different breast metastasis types may arise due to change in tissue microenvironment. To show the benefits of using structural PPI networks instead of traditional node and edge presentation, we inspect two case studies showing the mutual exclusiveness of interactions and effects of mutations on protein conformation which lead to different signaling.

Keywords: breast cancer, metastasis, PPI networks, protein conformational changes

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Authors: Nasim Nosoudi, Amir Zadeh, Hunter White, Joshua Conrad, Joon W. Shim

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De novo Malignancy has become one of the major causes of death after transplantation, so early cancer diagnosis and detection can drastically improve survival rates post-transplantation. Most previous work focuses on using artificial intelligence (AI) to predict transplant success or failure outcomes. In this work, we focused on predicting de novo malignancy after liver transplantation using AI. We chose the patients that had malignancy after liver transplantation with no history of malignancy pre-transplant. Their donors were cancer-free as well. We analyzed 254,200 patient profiles with post-transplant malignancy from the US Organ Procurement and Transplantation Network (OPTN). Several popular data mining methods were applied to the resultant dataset to build predictive models to characterize de novo malignancy after liver transplantation. Recipient's bilirubin, creatinine, weight, gender, number of days recipient was on the transplant waiting list, Epstein Barr Virus (EBV), International normalized ratio (INR), and ascites are among the most important factors affecting de novo malignancy after liver transplantation

Keywords: De novo malignancy, bilirubin, data mining, transplantation

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Authors: Sandeep Kumar Agrawal, Aditi Bhattacharya, Janvie Manhas, Krushna Bhatt, Yatin Kholakiya, Nupur Khera, Ajoy Roychoudhury, Sudip Sen

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Autologous cultured explants of human oral mucosal epithelial cells (OMEC) are a potential therapeutic modality for limbal stem cell deficiency (LSCD). Injury or inflammation of the ocular surface in the form of burns, chemicals, Stevens Johnson syndrome, ocular cicatricial pemphigoid etc. can lead to destruction and deficiency of limbal stem cells. LSCD manifests in the form of severe ocular surface diseases (OSD) characterized by persistent and recurrent epithelial defects, conjuntivalisation and neovascularisation of the corneal surface, scarring and ultimately opacity and blindness. Most of the cases of OSD are associated with severe dry eye pertaining to diminished mucin and aqueous secretion. Mycophenolate mofetil (MMF) has been shown to upregulate the mucin expression in conjunctival goblet cells in vitro. The aim of this study was to evaluate the effects of MMF on mucin expression in primary cultures of oral mucosal epithelial cells. With institutional ethics committee approval and written informed consent, thirty oral mucosal epithelial tissue samples were obtained from patients undergoing oral surgery for non-malignant conditions. OMEC were grown on human amniotic membrane (HAM, obtained from expecting mothers undergoing elective caesarean section) scaffold for 2 weeks in growth media containing DMEM & Ham’s F12 (1:1) with 10% FBS and growth factors. In vitro dosage of MMF was standardised by MTT assay. Analysis of stem cell markers was done using RT-PCR while mucin mRNA expression was quantified using RT-PCR and q-PCR before and after treating cultured OMEC with graded concentrations of MMF for 24 hours. Protein expression was validated using immunocytochemistry. Morphological studies revealed a confluent sheet of proliferating, stratified oral mucosal epithelial cells growing over the surface of HAM scaffold. The presence of progenitor stem cell markers (p63, p75, β1-Integrin and ABCG2) and cell surface associated mucins (MUC1, MUC15 and MUC16) were elucidated by RT-PCR. The mucin mRNA expression was found to be upregulated in MMF treated primary cultures of OMEC, compared to untreated controls as quantified by q-PCR with β-actin as internal reference gene. Increased MUC1 protein expression was validated by immunocytochemistry on representative samples. Our findings conclude that OMEC have the ability to form a multi-layered confluent sheet on the surface of HAM similar to a cornea, which is important for the reconstruction of the damaged ocular surface. Cultured OMEC has stem cell properties as demonstrated by stem cell markers. MMF can be a novel enhancer of mucin production in OMEC. It has the potential to improve dry eye in patients undergoing OMEC transplantation for bilateral OSD. Further clinical trials are required to establish the role of MMF in patients undergoing OMEC transplantation.

Keywords: limbal stem cell deficiency, mycophenolate mofetil, mucin, ocular surface disease

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Authors: Kristel Dame Bañez Sumagaysay, Marie Victoria Cruz-javier

Abstract:

The current subject is a case of a 21 year-old woman at 29 1/7 weeks of gestation with Pre-B cell Acute Lymphoblastic Leukemia who was admitted to the coronary care unit (CCU) of the St. Luke’s Medical Center-Global City for Severe Acute Respiratory Distress Syndrome (ARDS) secondary to hospital-acquired pneumonia secondary to pneumocystis jiroveci; central line-associated bloodstream infection (E. aerogenes). She presented with chronic hypoxemia caused by Pulmonary edema, probably secondary to heart failure secondary to cardiomyopathy chemotherapy-induced. Due to worsening feto-maternal status, extracorporeal membrane oxygenation (ECMO) for respiratory support was instituted, and an elective cesarean section was done due to multiple maternal factors and deteriorating health status under total intravenous anesthesia assisted by veno-venous extracorporeal membrane oxygenation. She delivered a live preterm newborn male, APGAR Score: 1, 0, 0, birth weight 985 grams, birth length: 40.5cm, small for gestational age.

Keywords: extracorporeal membrane oxygenation, pre-b cell acute lymphoblastic leukemia, severe acute respiratory distress syndrome, ethical dilemmas

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Authors: Hung-Chih Hsu, Pey-Jium Chang, Ching-Hsein Chen, Jer-Liang Andrew Yeh

Abstract:

Osteoarthritis (OA) is a common disorder in rehabilitation clinic. The main characteristics include joint pain, localized tenderness and enlargement, joint effusion, cartilage destruction, loss of adhesion of perichondrium, synovium hyperplasia. Synoviocytes inflammation might be a cause of local tenderness and effusion. Inflammation cytokines might also play an important role in joint pain, cartilage destruction, decrease adhesion of perichondrium to the bone. Treatments of osteoarthritis include non-steroid anti-inflammation drugs (NSAID), glucosamine supplementation, hyaluronic acid, arthroscopic debridement, and total joint replacement. Total joint replacement is commonly used in patients with severe OA who failed respond to pharmacological treatment. However, some patients received surgery had serious adverse events, including instability of the implants due to insufficient adhesion to the adjacent bony tissue or synovial inflammation. We tried to develop ideal nano-topographic oxidized silicon nanosponges by using with various chemicals to produce thickness difference in nanometers in order to study more about the cell-environment interactions in vitro like the alterations of cell adhesion, morphology, extracellular matrix secretions in the pathogenesis of osteoarthritis. Cytokines studies like growth factor, reactive oxygen species, reactive inflammatory materials (Like nitrous oxide and prostaglandin E2), extracellular matrix (ECM) degradation enzymes, and synthesis of collagen will also be observed and discussed. Extracellular and intracellular expression transforming growth factor beta (TGF-β) will be studied by reverse transcription-polymerase chain reaction (RT-PCR). The degradation of ECM will be observed by the bioactivity ratio of matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase by ELISA (Enzyme-linked immunosorbent assay). When rabbit synoviocytes were cultured on these nano-topographic structures, they demonstrate better cell adhesion rate, decreased expression of MMP-2,9 and PGE2, and increased expression of TGF-β when cultured in nano-topographic oxidized silicon nanosponges than in the planar oxidized silicon ones. These results show cell behavior, cytokine production can be influenced by physical characteristics from different nano-topographic structures. Our study demonstrates the possibility of manipulating cell behavior in these nano-topographic biomaterials.

Keywords: osteoarthritis, synoviocyte, oxidized silicon surfaces, reactive oxygen species

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Authors: Alessandra N. Santos, Max P. Ferreira, Alexandra R. P. Silva, Agda A. R. de Oliveira, Marivalda M. Pereira

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The literature describes experiments, in which ceria nanoparticles in the bioactive glass significantly improve differentiation of stem cells into osteoblasts and increase production of collagen. It is not known whether this effect observed due to the presence of nanoceria can be also observed in the presence of cerium in the bioactive glass network. The effect of cerium into bioactive glasses using the sol–gel route is the focus of this work, with the goal to develop a material for tissue engineering with the potential to enhance osteogenesis. A bioactive glass composition based on 70% SiO2–30% CaO is produced with the addition of cerium. The analyses XRD, FTIR, SEM/EDS, BET/BJH, in vitro bioactivity test and the Cell viability assay were performed. The results show that cerium remains in the bioactive glass structure. The obtained material present in vitro bioactivity and promote the cell viability.

Keywords: bioactive glass, bioactivity, cerium salt, material characterization, sol-gel method

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Authors: Ugo Rovigatti

Abstract:

Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

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Authors: Chia-Jung Li, Li-Te Lin, Kuan-Hao Tsui

Abstract:

The study identifies SPP1 as a potential gene associated with ovarian aging, revealing a significant decline in its expression in aged ovaries. SPP1, also known as osteopontin (OPN), is a multifunctional glycoprotein involved with regulatory proteins and pro-inflammatory immune chemokines. However, its genetic links to ovarian aging have not been extensively explored. Spatial transcriptomic analyses were conducted on ovaries from young and aged female mice, along with a sample from a 73-year-old individual. Additionally, single-cell RNA sequencing analysis was performed to identify associations between SPP1 and key genes. The study focused on crucial genes, including ITGAV, ITGB1, CD44, MMP3, and FN1, with a particular emphasis on the correlation between SPP1 and ITGB1. The findings indicate a significant decline in SPP1 expression in aged ovaries, which was consistent in the 73-year-old sample. Single-cell RNA sequencing unveiled associations between SPP1 and key genes, emphasizing a strong co-expression correlation between SPP1 and ITGB1. While the study provides valuable insights, further research is necessary to understand the broader implications and potential applications of SPP1 in ovarian aging. Translating these findings to clinical settings requires careful consideration. The identification of SPP1 as a gene implicated in ovarian aging opens new avenues for advancing precision medicine and refining treatment strategies for conditions related to ovarian aging.

Keywords: SPP1, ovarian aging, spatial transcriptomic, single-cell RNA sequencing

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Authors: Hitesh Gupta, Surender Dabas

Abstract:

TORS is increasingly gaining widespread use and has been explored as minimally invasive surgery for the treatment of supraglottic cancer (SGC). Being a central critical role of Supraglottis in deglutition, swallowing outcomes post TORS remain a most important factor. Available published studies show inconsistent swallowing outcomes and are deficient in standardized outcome measures, description of swallowing recovery and rehabilitation. So, the objective of this study is to find out swallowing outcomes in SGC patients after TORS provided with early dysphagia management using standardized measures. Prospectively 16 patients were recruited in the study who underwent TORS for primary tumor of Supraglottis, involving one or more sub-sites or invading to sites other than Supraglottis at the BLK Super Specialty Hospital, New Delhi from March 2019 to June 2020. All patients were evaluated for dysphagia with subsequent swallowing rehabilitation on post operative day 3 in the hospital or at the time of discharge, whichever was earlier. Functional oral intake scale (FOIS) and penetration-aspiration score (PAS) were used as outcome measures to quantify swallowing recovery at one month and six month post operatively. Post TORS, patients achieved functional swallow in less than one month, where resection was limited to Supraglottis, while the recovery was delayed in patients with extended resection to tongue base or hypopharynx. Overall, out of Total 16 cases including all supraglottis sub-catagories, 13 (81%) could remove their NG tube (FOIS ≥5 and PAS=1 ) within 6 months. In which 8 cases(62%) achieved functional swallow in less than one month. Swallowing outcomes post TORS supraglottic laryngectomy are favorable if provided with early dysphagia management (or swallowing rehabilitation).

Keywords: dysphagia, supraglottic cancer, swallowing, TORS

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