Search results for: differentiation period

Authors: Rajendra N. Ghosh, Paramjeet Singh, Niranjan Khandelwal, Sameer Vyas, Pratibha Singhi, Naveen Sankhyan

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Background: Tuberculoma and neurocysticercosis (NCC) are two most common intracranial infections in developing country. They often simulate on neuroimaging and in absence of typical imaging features cause significant diagnostic dilemmas. Differentiation is extremely important to avoid empirical exposure to antitubercular medications or nonspecific treatment causing disease progression. Purpose: Better characterization and differentiation of CNS tuberculoma and NCC by using morphological and multiple advanced functional MRI. Material and Methods: Total fifty untreated patients (20 tuberculoma and 30 NCC) were evaluated by using conventional and advanced sequences like CISS, SWI, DWI, DTI, Magnetization transfer (MT), T2Relaxometry (T2R), Perfusion and Spectroscopy. rCBV,ADC,FA,T2R,MTR values and metabolite ratios were calculated from lesion and normal parenchyma. Diagnosis was confirmed by typical biochemical, histopathological and imaging features. Results: CISS was most useful sequence for scolex detection (90% on CISS vs 73% on routine sequences). SWI showed higher scolex detection ability. Mean values of ADC, FA,T2R from core and rCBV from wall of lesion were significantly different in tuberculoma and NCC (P < 0.05). Mean values of rCBV, ADC, T2R and FA for tuberculoma and NCC were (3.36 vs1.3), (1.09x10⁻³vs 1.4x10⁻³), (0.13 x10⁻³ vs 0.09 x10⁻³) and (88.65 ms vs 272.3 ms) respectively. Tuberculomas showed high lipid peak, more choline and lower creatinine with Ch/Cr ratio > 1. T2R value was most significant parameter for differentiation. Cut off values for each significant parameters have proposed. Conclusion: Quantitative MRI in combination with conventional sequences can better characterize and differentiate similar appearing tuberculoma and NCC and may be incorporated in routine protocol which may avoid brain biopsy and empirical therapy.

Keywords: advanced functional MRI, differentiation, neurcysticercosis, tuberculoma

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Authors: Qing Cao, Fei Wang, Yu-Qiang Wang, Li-Ya Huang, Tian-Tian Sang, Shu-Yan Chen

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Aims: TNF Receptor-Associated Factor 6 (TRAF6) acts as a multifunctional regulator of the Transforming Growth Factor (TGF)-β signaling pathway, and mediates Smad-independent JNK and p38 activation via TGF-β. This study was performed to test the hypothesis that TGF-β/TRAF6 is essential for angiotensin-II (Ang II)-induced differentiation of rat c-kit+ Cardiac Stem Cells (CSCs). Methods and Results: c-kit+ CSCs were isolated from neonatal Sprague Dawley (SD) rats, and their c-kit status was confirmed with immunofluorescence staining. A TGF-β type I receptor inhibitor (SB431542) or the small interfering RNA (siRNA)-mediated knockdown of TRAF6 were used to investigate the role of TRAF6 in TGF-β signaling. Rescue of TRAF6 siRNA transfected cells with a 3'UTR deleted siRNA insensitive construct was conducted to rule out the off target effects of the siRNA. TRAF6 dominant negative (TRAF6DN) vector was constructed and used to infect c-kit+ CSCs, and western blotting was used to assess the expression of TRAF6, JNK, p38, cardiac-specific proteins, and Wnt signaling proteins. Physical interactions between TRAF6 and TGFβ receptors were studied by coimmunoprecipitation. Cardiac differentiation was suppressed in the absence of TRAF6. Forced expression of TRAF6 enhanced the expression of TGF-β-activated kinase1 (TAK1), and inhibited Wnt signaling. Furthermore, TRAF6 increased the expression of cardiac-specific proteins (cTnT and Cx-43) but inhibited the expression of Wnt3a. Conclusions: Our data suggest that TRAF6 plays an important role in Ang II induced differentiation of c-kit+ CSCs via the non-canonical signaling pathway.

Keywords: cardiac stem cells, differentiation, TGF-β, TRAF6, ubiquitination, Wnt

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Authors: Arefeh Jafarian, Mohammad Taghikani, Saied Abroun, Amir Allahverdi, Masoud Soleimani

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Introduction: The miRNAs have key roles in control of pancreatic islet development and insulin secretion. In this regards, current study investigated the pancreatic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) by up-regulation of miR-375 and down-regulation of miR-9 by lentiviruses containing miR-375 and anti-miR-9. Findings: After 21 days of induction, islet-like clusters containing insulin producing cells (IPCs) were confirmed by dithizone (DTZ) staining. The IPCs and β cell specific related genes and proteins were detected using qRT-PCR and immunofluorescence on days 7, 14 and 21 of differentiation. Glucose challenge test was performed at different concentrations of glucose as well as extracellular and intracellular insulin and C-peptide were assayed using ELISA kit. In derived IPCs by miR-375 alone are capable to express insulin and other endocrine specific transcription factors, the cells lack the machinery to respond to glucose. The differentiated hMSCs by miR-375 and anti-miR-9 lentiviruses could secrete insulin and c-peptide in a glucose-regulated manner. Conclusion: It was found that over-expression of miR-375 led to a reduction in levels of Mtpn protein in derived IPCs, while treatment with anti-miR-9 following miR-375 over-expression had synergistic effects on MSCs differentiation and insulin secretion in a glucose-regulated manner. The researchers reported that silencing of miR-9 increased OC-2 protein in IPCs that may contribute to the observed glucose-regulated insulin secretion. These findings highlight miRNAs functions in stem cells differentiation and suggest that they could be used as therapeutic tools for gene-based therapy in diabetes mellitus.

Keywords: diabetes, differentiation, MSCs, insulin producing cells, miR-375, miR-9

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Authors: Kathy Stein, Mariola Lysson, Anja Schmidt, Beatrix Schumak, Sabine Specht, Hicham Bouabe, Jürgen Heesemann, Axel Roers, Joerg C. Kalff, Sven Wehner

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Objective: Postoperative ileus (POI) is a common complication of abdominal surgery. Monocyte infiltration is a hallmark of POI. The polarization of macrophages/monocytes in this process is not well understood. We aimed to investigate if and how M2 macrophage/monocyte differentiation is involved in POI pathogenesis. Design: POI was induced by intestinal manipulation (IM). C57Bl/6, CCR2-/-, IL-10 reporter (ITIB), IL-10-/- and LysMcre/IL-10fl/fl mice underwent IM. At various points in time leukocyte influx, gene and protein expression of cytokines, chemokines and M2 differentiation markers and intestinal motility were analyzed. Results: IM induced the postoperative expression of the M2 markers Arginase-1 and YM-1, predominantly in F4/80+Ly6C+ monocytes. Gene expression analyses indicated an IL-10-dependent, IL-4-independent M2 polarization of these monocytes. IL-10 dependency of M2 differentiation was confirmed in IL-10 deficient mice. Leukocytes, in the order of infiltrating monocytes, neutrophils, and resident macrophages were the main IL-10 producers during POI. IL-10 producing monocytes as well as M2 marker expression were almost absent in CCR2-deficient mice. However, postoperative IL-10 expression was not altered in CCR2-/- mice. The loss of M2 polarized monocytes neither protected CCR2-/- mice from nor affected resolution of POI. In contrast, IL-10 deficiency reduced postoperative neutrophil numbers and ameliorated POI. IL-10Ra expression was strongly induced in neutrophils but not in monocytes. Conclusion: We conclude that IL-10 counteracts POI resolution by activating IL-10Ra-expressing neutrophils in the late phase of disease while IL-10-dependent M2 differentiation is not pivotal to POI manifestation and resolution.

Keywords: interleukin-10, macrophages, neutrophils, postoperative ileus

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Authors: Mohamed Suleiman, Zarina Bibi Ibrahim, Nor Ain Azeany, Khairil Iskandar Othman

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In this paper, a class of variable order fully implicit multistep Block Backward Differentiation Formulas (VOBBDF) using uniform step size for the numerical solution of stiff ordinary differential equations (ODEs) is developed. The code will combine three multistep block methods of order four, five and six. The order selection is based on approximation of the local errors with specific tolerance. These methods are constructed to produce two approximate solutions simultaneously at each iteration in order to further increase the efficiency. The proposed VOBBDF is validated through numerical results on some standard problems found in the literature and comparisons are made with single order Block Backward Differentiation Formula (BBDF). Numerical results shows the advantage of using VOBBDF for solving ODEs.

Keywords: block backward differentiation formulas, uniform step size, ordinary differential equations

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Authors: Igor Sukhotnik

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Objectives: Notch signaling is thought to act to drive cell versification in the lining of the small intestine. When Notch signaling is blocked, proliferation ceases, and epithelial cells become secretory. The purpose of the present study was to evaluate the role of Notch signaling pathway in stem cell differentiation in a rat model of intestinal ischemia-reperfusion (IR). Methods: Male Sprague-Dawley rats were randomly divided into four experimental groups: Sham-24 and Sham-48 rats underwent laparotomy and were killed 24 or 48 h later, respectively; IR-24 and IR-48 rats underwent occlusion of SMA and portal vein for 30 min followed by 24 or 48 h of reperfusion, respectively. Notch-related gene and protein expression were determined using Real Time PCR, Western blotting and immunohistochemistry. Wax histology and immunohistochemistry was used to determine cell differentiation toward absorptive (enterocytes) or secretory progenitors (goblet cells, enteroendocrine cells or Paneth cells). Results: IR-48 rats exhibited a significant decrease in Notch-1 protein expression (Western blot) that was coincided with a significant decrease in the number of Notch-1 positive cells (immunohistochemistry) in jejunum and ileum as well as Hes-1 positive cells in jejunum and ileum compared to Sham-48 rats. A significant down-regulation of Notch signaling related genes and proteins in IR animals was accompanied by a significant increase in the number of goblet and Paneth cells and decreased number of absorptive cells compared to control rats. Conclusions: Forty-eight hours following intestinal IR in rats, inhibited Notch signaling pathway was accompanied by intestinal stem cells differentiation toward secretory progenitors.

Keywords: Intestine, notch, ischemia-reperfusion, cell differentiation, secretory

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Authors: Mariam Shah

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‘Honour’ crime has commonly been perceived in the UK as being a ‘domestic violence’ related issue due to incidents perceived to take place within a domestic context, and commonly by familial perpetrators. The lack of differentiation between domestic violence and ‘honour’ related incidents has several negative implications. Firstly, the prevalence and extent of ‘honour’ related crime within the UK cannot be accurately quantified due to ‘honour’ incidents being classed statistically as domestic violence incidents. Secondly, lack of differentiation means that the negative stereotypical attitudes ascribed to domestic violence which has resulted in lower criminal conviction rates that are also impacting the conviction of perpetrators of ‘honour’ crime. Thirdly, ‘honour’ related crime is innately distinct from domestic violence due to the perpetrator’s resolute intent of cleansing perceived ‘shame’ in any way possible, often with the involvement and collusion of multiple perpetrators from within the family and/or community. Domestic violence is typically restricted to the ‘home’, but ‘honour’ crime can operate between national and international boundaries. This paper critically examines the current academic literature and concludes that the few similarities between domestic violence and ‘honour’ related crime are not sufficient to warrant identical treatment under UK criminal law. ‘Honour’ related crime is a distinct and stand-alone offence which should be recognised as such. The appropriate identification and treatment of ‘honour’ crime are crucial, particularly in light of the UK’s first ‘white’ honour killing which saw a young English woman murdered after being deemed to have brought ‘shame’ on her ex-boyfriend’s family. This incident highlights the possibility of ‘honour’ crime extending beyond its perceived ‘ethnic minority’ roots and becoming more of a ‘mainstream’ issue for the multi-cultural and multi-racial UK.

Keywords: differentiation, domestic violence, honour crime, United Kingdom

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Authors: Noshaba Dilbar, Aisha Tahir, Amer Jamil

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During the last decade, DNA barcoding proved to be an authentic tool for discovery and identification of plants. In the present study, DNA barcoding of two species, Fagonia arabica and Fagonia indica was done for differentiation by using matK region. matK gene is considered as a universal barcode because of its easy alignment and high discrimination ability. In this study, matK yielded 100% sequencing results. The sequences from both plants were aligned at clustal W and observed that there is no nucleotide variation and polymorphism among both sequences. This was further analysed by BLAST which showed the similar sequences from different plants belonging to same family but didn’t find sequence of both species. Considering this, the resulted sequence was submitted by the name of Fagonia arabica with accession number KM276890. In the end, we analysed the results from BOLD which gave us the final conclusion that both plants are same as their matK sequences are 100% identical. In literature, both Fagonia indica and Fagonia arabica names are used for this plant but there is no clear differentiation has been observed in these plants. Results evaluate that Fagonia indica and Fagonia arabica are the alternative names of same plant.

Keywords: DNA barcoding, Fagonia arabica, Fagonia indica, matK

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Authors: Lu-Chen Yeh‚ Jui-Ming Yeh

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In this manuscript, we produced neat electrospun poly(o-methoxyaniline) (POMA) fibers and utilized it for applying the growth of neural stem cells. The transparency and morphology of as-prepared POMA fibers were characterized by UV-visible spectroscopy and scanning electron microscopy, respectively. It was found to have no adverse effects on the long-term proliferation of the neural stem cells (NSCs), retained the ability to self-renew, and exhibit multi-potentiality. Results of immunofluorescence staining studies confirmed that POMA electrospun fibers could provide a great environment for NSCs and enhance its differentiation.

Keywords: electrospun, polyaniline, neural stem cell, differentiation

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Authors: Valerie Yocco Rossi

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Objective: The author will share why differentiation is necessary for all classrooms as well as strategies for differentiating content, process, and product. Through learning how to differentiate, teachers will be able to create activities and assessments to meet the abilities, readiness levels, and interests of all learners. Content and Purpose: This work will focus on how to create a learning experience for students that recognizes their different interests, abilities, and readiness levels by differentiating content, process, and product. Likewise, the best learning environments allow for choice. Choice boards allow students to select tasks based on interests. There can be challenging and basic tasks to meet the needs of various abilities. Equally, rubrics allow for personalized and differentiated assessments based on readiness levels and cognitive abilities. The principals of DI help to create a classroom where all students are learning to the best of their abilities. Outcomes: After reviewing the work, readers will be able to (1) identify the benefits of differentiated instruction; (2) convert traditional learning activities to differentiated ones; (3) differentiate, writing-based assessments.

Keywords: differentiation, personalized learning, design, instructional strategies

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Authors: Hanife Genç

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This study was conducted to determine sex differentiation of laboratory reared Elm nymphalid (Nymphalis polychloros Linnaeus, 1758) by examining the morphological structure of pupal stage. Laboratory colony of elm nymphalid, reared on pear leaves, were used to set up experiments. It was performed with 5 replications having 8 pupae for each replication. Dorsal, ventral and lateral parts of external morphological structures of pupae were examined by Olympus SZX9 microscope and photographed. When fully grown, mature larvae wander the highest part of the rearing cage and pupae were formed hanging by cremaster. After completing prepupa stage about 1.5±0.3 days, they all pupated. Pupal stage was completed at 25±1°C about 4.38±1.20 days. Pupal weights were 0.483±0.05 g in females and 0.392±0.08 g (n=40) in males respectively. Pupal emergence rate was 95%, with 22 females and 16 males. Examinations of ventral parts of 8th, 9th, and 10th abdominal segments revealed that anal opening were found at 10th abdominal segment in both sexes, 3 lumbs were determined at 9th abdominal segments then the specific opening structure at 8th segment was only found on female pupae.

Keywords: sex differentiation, Nymphalis polychloros, pupa, Linnaeus

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Authors: Dhruv J. Limaye, Hanga Galfalvy, Cheick A. Sissoko, Yung-yu Huang, Chunanning Tang, Ying Liu, Shu-Chi Hsiung, Andrew J. Dwork, Gorazd B. Rosoklija, Victoria Arango, Lewis Brown, J. John Mann, Maura Boldrini

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Memory and emotion require hippocampal cell viability and connectivity and are disrupted in major depressive disorder (MDD). Applying shotgun proteomics and stereological quantification of neural progenitor cells (NPCs), intermediate neural progenitors (INPs), and mature granule neurons (GNs), to postmortem human hippocampus, identified differentially expressed proteins (DEPs), and fewer NPCs, INPs and GNs, in untreated MDD (uMDD) compared with non-psychiatric controls (CTRL) and antidepressant-treated MDD (MDDT). DEPs lower in uMDD vs. CTRL promote mitosis, differentiation, and prevent apoptosis. DEPs higher in uMDD vs. CTRL inhibit the cell cycle, and regulate cell adhesion, neurite outgrowth, and DNA repair. DEPs lower in MDDT vs. uMDD block cell proliferation. We observe group-specific correlations between numbers of NPCs, INPs, and GNs and an abundance of proteins regulating mitosis, differentiation, and apoptosis. Altered protein expression underlies hippocampus cellular and volume loss in uMDD, supports a trophic effect of antidepressants, and offers new treatment targets.

Keywords: proteomics, hippocampus, depression, mitosis, migration, differentiation, mitochondria, apoptosis, antidepressants, human brain

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Authors: Sizhu Wang, Cuisong Tang, Lin Zhang, Guangyu Tang

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Objective: We aimed to detect the composition of bone marrow fatty acids early after ovariectomized (OVX) surgery and explore the potential mechanism. Methods: Thirty-two female Sprague-Dawley (SD) rats (12 weeks) were randomly divided into OVX group and Sham group (N=16/group), and received ovariectomy or sham surgery respectively. After 3 and 28 days, eight rats in each group were sacrificed to detect the composition of bone marrow fatty acids by gas chromatography–mass spectrometry (GC–MS) and evaluate the trabecular bone microarchitecture by micro-CT. Significant different fatty acids in the early stage of post-menopausal osteoporosis were selected by OPLS-DA and t test. Then selected fatty acids were further studied in the process of osteogenic differentiation through RT-PCR and Alizarin Red S staining. Results: An apparent sample clustering and group separation were observed between OVX group and sham group three days after surgery, which suggested the role of bone marrow fatty acids in the early stage of postmenopausal osteoporosis. Specifically, myristate, palmitoleate and arachidonate were found to play an important role in classification between OVX group and sham group. We further investigated the effect of palmitoleate and arachidonate on osteogenic differentiation and found that palmitoleate promoted the osteogenic differentiation of MC3T3-E1 cells while arachidonate inhibited this process. Conclusion: Profound bone marrow fatty acids changes have taken place in the early stage of post-menopausal osteoporosis. Bone marrow fatty acids may begin to affect osteogenic differentiation shortly after deficiency of estrogen.

Keywords: bone marrow fatty acids, GC-MS, osteoblast, osteoporosis, post-menopausal

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: Simon Grossemy, Peggy P. Y. Chan, Pauline M. Doran

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Nerve tissue engineering is the main field of research aimed at finding an alternative to autografts as a treatment for nerve injuries. Scaffolds are used as a support to enhance nerve regeneration. In order to successfully design novel scaffolds and in vitro cell culture systems, a deep understanding of the factors affecting nerve regeneration processes is needed. Physical and biological parameters associated with the culture environment have been identified as potentially influential in nerve cell differentiation, including electrical stimulation, exposure to extracellular-matrix (ECM) proteins, dynamic medium conditions and co-culture with glial cells. The mechanisms involved in driving the cell to differentiation in the presence of these factors are poorly understood; the complexity of each of them raises the possibility that they may strongly influence each other. Some questions that arise in investigating nerve regeneration include: What are the best protein coatings to promote neural cell attachment? Is the scaffold design suitable for providing all the required factors combined? What is the influence of dynamic stimulation on cell viability and differentiation? In order to study these effects, scaffolds adaptable to bioreactor culture conditions were designed to allow electrical stimulation of cells exposed to ECM proteins, all within a dynamic medium environment. Gold coatings were used to make the surface of viscose rayon microfiber scaffolds (VRMS) conductive, and poly-L-lysine (PLL) and laminin (LN) surface coatings were used to mimic the ECM environment and allow the attachment of rat PC12 neural cells. The robustness of the coatings was analyzed by surface resistivity measurements, scanning electron microscope (SEM) observation and immunocytochemistry. Cell attachment to protein coatings of PLL, LN and PLL+LN was studied using DNA quantification with Hoechst. The double coating of PLL+LN was selected based on high levels of PC12 cell attachment and the reported advantages of laminin for neural differentiation. The underlying gold coatings were shown to be biocompatible using cell proliferation and live/dead staining assays. Coatings exhibiting stable properties over time under dynamic fluid conditions were developed; indeed, cell attachment and the conductive power of the scaffolds were maintained over 2 weeks of bioreactor operation. These scaffolds are promising research tools for understanding complex neural cell behavior. They have been used to investigate major factors in the physical culture environment that affect nerve cell viability and differentiation, including electrical stimulation, bioreactor hydrodynamic conditions, and combinations of these parameters. The cell and tissue differentiation response was evaluated using DNA quantification, immunocytochemistry, RT-qPCR and functional analyses.

Keywords: bioreactor, electrical stimulation, nerve differentiation, PC12 cells, scaffold

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Authors: Ajda Osifo, Fatma Elshafie

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Mobile-assisted language learning favors social-constructivist and connectivist theories to learning and adaptive approaches to teaching. It offers many opportunities to differentiated instruction in meaningful ways as it enables learners to become more collaborative, engaged and independent through additional dimensions such as web-based media, virtual learning environments, online publishing to an imagined audience and digitally mediated communication. MALL applications can be a tool for the teacher to personalize and adjust instruction according to the learners’ needs and give continuous feedback to improve learning and performance in the process, which support differentiated instruction practices. This paper explores the utilization of Mobile Assisted Language Learning applications as a supporting tool for effective differentiation in the language classroom. It reports overall experience in terms of implementing MALL to shape and apply differentiated instruction and expand learning options. This session is structured in three main parts: first, a review of literature and effective practice of academically responsive instruction will be discussed. Second, samples of differentiated tasks, activities, projects and learner work will be demonstrated with relevant learning outcomes and learners’ survey results. Finally, project findings and conclusions will be given.

Keywords: academically responsive instruction, differentiation, mobile learning, mobile-assisted language learning

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

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

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

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Authors: Sona Babu Rathinam, Lavanya Dharmendran, Therraddi Mutthu

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Objectives: The purpose of this paper is to provides an overview of the neuroendocrine tumors that arise in the oral cavity. Material and Methods: An overview of the relevant papers on neuroendocrine tumors of the oral cavity by various authors was studied and summarized. Results: On the basis of the relevant studies, this paper provides an overview of the classification and histological differentiation of the neuroendocrine tumors that arise in the oral cavity. Conclusions: The basis of classification of neuroendocrine tumors is largely determined by their histologic differentiation. Though they reveal biologic heterogeneity, there should be an awareness of the occurrence of such lesions in the oral cavity to enable them to be detected and treated early.

Keywords: malignant peripheral nerve sheath tumor, olfactory neuroblastoma, paraganglioma, schwannoma

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Authors: Yu-Chen Hu

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Gene editing by CRISPR and gene regulation by microRNA or CRISPR activation have dramatically changed the way to manipulate cellular gene expression and cell fate. In recent years, various gene editing and gene manipulation technologies have been applied to control stem cell differentiation to enhance tissue regeneration. This research will focus on how to develop CRISPR, CRISPR activation (CRISPRa), CRISPR inhibition (CRISPRi), as well as bi-directional CRISPR-AI gene regulation technologies to control cell differentiation and bone regeneration. Moreover, in this study, CRISPR/Cas13d-mediated RNA editng for miRNA editing and bone regeneration will be discussed.

Keywords: gene therapy, bone regeneration, stem cell, CRISPR, gene regulation

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Authors: Rui G. Serôdio, Carina Martins, Alexandra Serra, José A. Lima, Luísa Catita, Paula Lopes

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Building on social identity approach, we tested the impact of social categorization and comparison in the psychosocial process by which social entrepreneurs define their group identity. Specifically, we address how both differentiation and assimilation processes are set of in the context of constructing a novel, distinctive and socially salient – social entrepreneurs. As part of a larger research line, a quasi-experimental study with Social and Business Entrepreneurs, as well as “Lay People” provided evidence consistent with our predictions: (1) Social Entrepreneurs, in contrast with Lay People and Business Entrepreneurs, value more strongly social identity than personal identity, and the later is the only group that values Personal Differentiation; (2) unlike Entrepreneurs, Social Entrepreneurs display an ingroup bias across group evaluations; (3) Lay People, display a self-serving bias, although, overall, they allocate a more positive image to the target groups; (4) combining own vs. others evaluations across all groups, Social Entrepreneurs receive the more positive value. From the standpoint of social identity and self-categorization theories and their approach to group process, we discuss the processes of intergroup comparison and differentiation as core processes in the construction of a positive social identity. We illustrate it within the context of social entrepreneurship, a political and social “wave” that flows across Europe at this time.

Keywords: group processes, social entrepreneurship, social identity, business entrepreneurs

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Authors: Magdalena Kowalska, Weronika Rupik

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The pancreas is an important organ present in all vertebrate species. It contains two different tissues, exocrine and endocrine, that act as two glands in one. The development and differentiation of the pancreas in reptiles is poorly known in comparison to other vertebrates. Therefore, the aim of this study was to investigate the particular steps concerning the differentiation of the pancreas in the grass snake (Natrix natrix) embryos. For this, histological methods (including hematoxylin and eosin, and Heidenhain's AZAN staining), transmission electron microscopy and three-dimensional (3D) reconstructions from serial paraffin sections were used. The results of this study indicated that the first step of pancreas development in Natrix was the connection of the two pancreatic buds: dorsal and ventral one. Then, duct walls in both buds started to be remodeled from the multilayered to single-layered epithelium. This remodeling started in the dorsal bud and was simultaneously with the differentiation of the duct lumens which occurred by the cavition. During this process, the cells that had no contact with the mesenchyme underwent cell death named anoikis. These findings indicated that the walls of ducts in the embryonic pancreas of the grass snake were initially formed by the abundant principal and single endocrine cells. Later the basal and goblet cells differentiated. Among the endocrine cells, as the first the B and A cells differentiated, then the D and PP cells. The next step of the pancreatic development was the withdrawing of the endocrine cells from the duct walls to form the pancreatic islets. The endocrine cells and islets were found only in the dorsal part of the pancreas in Natrix embryos what is different than in other vertebrate species. The islets were formed mainly by the A cells. Simultaneously, with the differentiation of the endocrine pancreas, the acinar tissue started to differentiate. The source of the acinar cells were pancreatic ducts similar as in other vertebrates. The acini formation began at the proximal part of the pancreas and went towards the caudal direction. Differentiating pancreatic ducts developed into the branched system that can be divided into extralobular, intralobular, and intercalated ducts, similarly as in other vertebrate species. However, the pattern of branching was different. In conclusions, particular steps of the pancreas differentiation in the grass snake were different than in other vertebrates. It can be supposed that these differences are related to the specific topography of the snake’s internal organs and their taxonomy position. All specimens used in the study were captured according to the Polish regulations concerning the protection of wild species. Permission was granted by the Local Ethics Commission in Katowice (41/2010; 87/2015) and the Regional Directorate for Environmental Protection in Katowice (WPN.6401.257.2015.DC).

Keywords: embryogenesis, organogenesis, pancreas, Squamata

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Authors: Chun Hsien Wu, Guan Xuan Wu, Hsia Ying Cheng, Shyh Ming Kuo

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Articular cartilage is composed of chondrocytes and extracellular matrix, such as collagen fibers, glycosaminoglycans, etc., which play an important role in lubricating and cushion joint activities. The phenotypic expression and metabolic activity of chondrocytes are extremely important in maintaining the functions of articular cartilage. In in vitro passaged culture of chondrocytes, chondrocytes gradually lose their original cell phenotype and morphology, which is called dedifferentiation. After continuous passaged culture of chondrocytes or induction by inflammatory factor IL-1, chondrocytes changed their phenotype and morphology. Also, the extracellular matrix type II collagen and GAG secretion were significantly reduced, while type I and X collagen were synthesized. Farnesol is an anti-inflammatory and antioxidant sesquiterpene compound that has the specific property of promoting collagen production. The purpose of this study was to investigate whether farnesol could restore the original type II collagen synthesis and, furthermore, the mechanisms of farnesol on the synthesis of type II collagen from the de-differentiated chondrocytes. The obtained results showed that the de-differentiated chondrocytes significantly restored to secret type II collagen and GAG (2.5-folds increases), and the secretion of collagen I and X and PGE2 synthesis were also significantly reduced after being treated with farnesol, indicating that farnesol had a restoration/re-differentiation effect on de-differentiated chondrocytes. The de-differentiated chondrocytes exhibited decreased expression of PPAR-γ and upregulated TGF-β expression to increase the MMP-13 expression. Higher expression of MMP-13 caused chondrocytes to secret type X collagen. On the contrary, increasing the expression of PPAR-γ would benefit the production of type II collagen. As shown, the PPAR-γ expression increased, and MMP-13 expression decreased after being treated with farnesol, indicating a possible signal pathway of farnesol to restore the production of type II collagen. However, more detailed mechanisms still need to evaluate.

Keywords: chondrocytes, de-differentiation, farnesol, re-differentiation

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Authors: Lina Liang, Kai Xu, Jing Zhang

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Purpose: Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement is discussed as a potential therapy for AMD. Besides intravitreal injection and subretinal injection, intravenous administration has been explored as an alternative route. This study is to observe the effect of BSYJ, a traditional Chinese medicine on the homing and differentiation of mesenchymal stem cells transplanted via tail vein injection in an age-related macular degeneration mouse model. Methods: Four-week-old C57BL/6J mice were injected with 40 mg/kg NaIO₃ to induce age-related macular degeneration model. At the second day after NaIO₃ injection, 1×10⁷ GFP labeled bone marrow-derived mesenchymal stem cells (GFP-MSCs) were transplanted via tali vein injection into the experimental mice. Then the mice were randomly divided into two groups, gavaged with either BSYJ solution (BSYJ group, n=12) or distilled water (DW group, n=12). 12 age-matched healthy C57BL/6J mice were fed regularly as normal control. At day 7, day 14, and day 28 after treatment, retina flat mounting was used to detect the homing of mesenchymal stem cells at the retina. Double-labeling immunofluorescence was used to determine the differentiation of mesenchymal stem cells. Results: At 7, 14, 28 days after treatment, the numbers of GFP-MSCs detected by retina flatmount were 10.2 ± 2.5, 14.5 ± 3.4 and 18.7 ± 5.8, respectively in the distilled water group, while 15.7 ± 3.8, 32.3 ± 3.5 and 77.3 ± 6.4 in BSYJ group, the differences between the two groups were significant (p < 0.05). At 28 days after treatment, it was shown by double staining immunofluorescence that there were more GFP positive cells in the retina of BSYJ group than that of the DW group, but none of the cells expressed RPE specific genes such as RPE65 and CRALBP, or photoreceptor genes such as recoverin and rhodopsin either in BSYJ group or DW group. However, GFAP positive cells were found among the cells labeled with GFP, and the double labeling cells were much more in the BSYJ group than the distilled water group. Conclusion: BSYJ could promote homing of mesenchymal stem cells at the retina of age-related macular degeneration model mice induced by NaIO₃, and the differentiation towards to glial cells. Acknowledgement: National Natural Foundation of China (No: 81473736, 81674033,81973912).

Keywords: BSYJ, differentiation, homing, mesenchymal stem cells

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Authors: Husain S. Yawer, Vasim Raja Panwar, Nidhi Priya

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The objective of this study is to evaluate and compare the role of nano-gelatin and Bioengineered Scaffolds on the attachment, proliferation, and osteogenic differentiation of human dental pulp stem cells (DPSCs). Tooth decay and early fall have each been one of the most prevailing dental disorders which cause physical and emotional suffering and compromise the patient's quality of life. The design of novel scaffolding materials will be based on mimicking the architecture of natural dental extracellular matrix which may provide as in vivo environments for proper cell growth. This methodology will involve the combination of nano-fibred gelatin as well as biodegradable hydrogel based tooth scaffold. We have measured and optimized the Dental Pulp Stem Cells growth profile in cultures carried out on collagen-coated plastic surface, however, for tissue regeneration study, we aim to develop an enhanced microenvironment for stem cell growth and dental tissue regeneration. We believe biomimetic cell adhesion and scaffolds might provide a near in vivo growth environment for proper growth and differentiation of human DPSCs, which further help in dentin/pulp tissue regeneration.

Keywords: nano-gelatin, stem cells, dental pulp, scaffold

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Authors: H. C. Chinwenyi, H. D. Ibrahim, J. O. Adekunle

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The incubation period is defined as the time from infection with a microorganism to development of symptoms. In this research, two disease models: one with incubation period and another without incubation period were studied. The study involves the use of a  mathematical model with a single incubation period. The test for the existence and stability of the disease free and the endemic equilibrium states for both models were carried out. The fourth order Runge-Kutta method was used to solve both models numerically. Finally, a computer program in MATLAB was developed to run the numerical experiments. From the results, we are able to show that the endemic equilibrium state of the model with incubation period is locally asymptotically stable whereas the endemic equilibrium state of the model without incubation period is unstable under certain conditions on the given model parameters. It was also established that the disease free equilibrium states of the model with and without incubation period are locally asymptotically stable. Furthermore, results from numerical experiments using empirical data obtained from Nigeria Centre for Disease Control (NCDC) showed that the overall population of the infected people for the model with incubation period is higher than that without incubation period. We also established from the results obtained that as the transmission rate from susceptible to infected population increases, the peak values of the infected population for the model with incubation period decrease and are always less than those for the model without incubation period.

Keywords: asymptotic stability, Hartman-Grobman stability criterion, incubation period, Routh-Hurwitz criterion, Runge-Kutta method

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Authors: Santi Termprasertsakul, Jakkrich Jearviriyaboonya

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This paper studies the market power and pricing behavior of products in iron and steel industry by investigating the impact of vertical product differentiation (VPD) on exchange rate pass-through (ERPT). Vietnam has become one of the major trading partners of Thailand since 2017. The iron and steel export value to Vietnam is more than $300 million a year. Particularly, the average growth rate of importing iron and steel is approximately 30% per year. The VPD is applied to analyze the quality difference of iron and steel between Thailand and Vietnam. The 20 products in iron and steel industry are investigated. The monthly pricing behavior of Harmonized Commodity Description and Coding System 4-digit products is observed from 2010 to 2019. The Nonlinear Autoregressive Distributed Lag is also used to analyze the asymmetry of ERPT in this paper. The empirical results basically reveal an incomplete pass-through between Thai Baht and Vietnamese Dong. The ERPT also varies with the degree of VPD. The product with higher VPD, indicating higher unit values, has higher ERPT. This result suggests the higher market power of the Thai iron and steel industry. In addition, the asymmetry of ERPT exists.

Keywords: exchange rate pass-through, iron and steel industry, pricing behavior, vertical product differentiation

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Authors: Ling-Ling E, Lin Feng, Hong-Chen Liu, Dong-Sheng Wang, Zhanping Shi, Juncheng Wang, Wei Luo, Yan Lv

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The objective of this study was to compare the effects of the two calcium phosphate composite scaffolds on the attachment, proliferation and osteogenic differentiation of rabbit dental pulp stem cells (DPSCs). One nano-hydroxyapatite/collagen/poly (L-lactide) (nHAC/PLA), imitating the composition and the micro-structure characteristics of the natural bone, was made by Beijing Allgens Medical Science & Technology Co., Ltd. (China). The other beta-tricalcium phosphate (β-TCP), being fully interoperability globular pore structure, was provided by Shanghai Bio-lu Biomaterials Co, Ltd. (China). We compared the absorption water rate and the protein adsorption rate of two scaffolds and the characterization of DPSCs cultured on the culture plate and both scaffolds under osteogenic differentiation media (ODM) treatment. The constructs were then implanted subcutaneously into the back of severe combined immunodeficient (SCID) mice for 8 and 12 weeks to compare their bone formation capacity. The results showed that the ODM-treated DPSCs expressed osteocalcin (OCN), bone sialoprotein (BSP), type I collagen (COLI) and osteopontin (OPN) by immunofluorescence staining. Positive alkaline phosphatase (ALP) staining, calcium deposition and calcium nodules were also observed on the ODM-treated DPSCs. The nHAC/PLA had significantly higher absorption water rate and protein adsorption rate than ß-TCP. The initial attachment of DPSCs seeded onto nHAC/PLA was significantly higher than that onto ß-TCP; and the proliferation rate of the cells was significantly higher than that of ß-TCP on 1, 3 and 7 days of cell culture. DPSCs+ß-TCP had significantly higher ALP activity, calcium/phosphorus content and mineral formation than DPSCs+nHAC/PLA. When implanted into the back of SCID mice, nHAC/PLA alone had no new bone formation, newly formed mature bone and osteoid were only observed in β-TCP alone, DPSCs+nHAC/PLA and DPSCs+β-TCP, and this three groups displayed increased bone formation over the 12-week period. The percentage of total bone formation area had no difference between DPSCs+β-TCP and DPSCs+nHAC/PLA at each time point，but the percentage of mature bone formation area of DPSCs+β-TCP was significantly higher than that of DPSCs+nHAC/PLA. Our results demonstrated that the DPSCs on nHAC/PLA had a better proliferation and that the DPSCs on β-TCP had a more mineralization in vitro, much more newly formed mature bones in vivo were presented in DPSCs+β-TCP group. These findings have provided a further knowledge that scaffold architecture has a different influence on the attachment, proliferation and differentiation of cells. This study may provide insight into the clinical periodontal bone tissue repair with DPSCs+β-TCP construct.

Keywords: dental pulp stem cells, nano-hydroxyapatite/collagen/poly(L-lactide), beta-tricalcium phosphate, periodontal tissue engineering, bone regeneration

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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: Zeytu G. Asfaw, Serkalem K. Abrha, Demisew G. Degefu

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Background: HIV/AIDS remains a major public health problem in Ethiopia and heavily affecting people of productive and reproductive age. We aimed to compare the performance of Parametric Survival Analysis and Bayesian Survival Analysis using simulations and in a real dataset application focused on determining predictors of HIV patient survival. Methods: A Parametric Survival Models - Exponential, Weibull, Log-normal, Log-logistic, Gompertz and Generalized gamma distributions were considered. Simulation study was carried out with two different algorithms that were informative and noninformative priors. A retrospective cohort study was implemented for HIV infected patients under Highly Active Antiretroviral Therapy in Alamata General Hospital, North Ethiopia. Results: A total of 320 HIV patients were included in the study where 52.19% females and 47.81% males. According to Kaplan-Meier survival estimates for the two sex groups, females has shown better survival time in comparison with their male counterparts. The median survival time of HIV patients was 79 months. During the follow-up period 89 (27.81%) deaths and 231 (72.19%) censored individuals registered. The average baseline cluster of differentiation 4 (CD4) cells count for HIV/AIDS patients were 126.01 but after a three-year antiretroviral therapy follow-up the average cluster of differentiation 4 (CD4) cells counts were 305.74, which was quite encouraging. Age, functional status, tuberculosis screen, past opportunistic infection, baseline cluster of differentiation 4 (CD4) cells, World Health Organization clinical stage, sex, marital status, employment status, occupation type, baseline weight were found statistically significant factors for longer survival of HIV patients. The standard error of all covariate in Bayesian log-normal survival model is less than the classical one. Hence, Bayesian survival analysis showed better performance than classical parametric survival analysis, when subjective data analysis was performed by considering expert opinions and historical knowledge about the parameters. Conclusions: Thus, HIV/AIDS patient mortality rate could be reduced through timely antiretroviral therapy with special care on the potential factors. Moreover, Bayesian log-normal survival model was preferable than the classical log-normal survival model for determining predictors of HIV patients survival.

Keywords: antiretroviral therapy (ART), Bayesian analysis, HIV, log-normal, parametric survival models

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Authors: Burkhard Hehenkamp, Tahmina Faizi

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In this paper, we analyze the formation of cartels along with the stability of the cartel for the case of three firms that produce differentiated products and differ in their cost of production. Both cost and demand are linear, and firms compete in quantities once a cartel has been formed (or not). It turns out that the degree of product differentiation has a direct effect on the incentive to form a cartel. Firstly, when goods are complements or close substitutes, firms form a grand coalition. Secondly, for weak and medium substitutes, the firm with the lowest cost prefers to remain independent, while both other firms form a coalition. We also find that the producer profit of the stable coalition structure is nonmonotonic in the degree of product differentiation.

Keywords: collusion, cartel formation, cartel stability, differentiated market, quantity competition, oligopolies

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