Ascorbic Acid, Inflammatory Cytokines (IL-1β/TNF-α/IFN-γ), or Their Combination’s Effect on Stemness, Proliferation, and Differentiation of Gingival Mesenchymal Stem/Progenitor Cells

Objective. Ascorbic acid (AA) and controlled inflammatory stimuli are postulated to possess the ability to independently exert positive effects on a variety of proliferative, pluripotency, and differentiation attributes of gingival mesenchymal stem/progenitor cells (G-MSCs). The current study’s objective was to explore and compare for the first time the impact of the major inflammatory cytokines (IL-1β/TNF-α/IFN-γ), AA, or their combination on multipotency/pluripotency, proliferative, and differentiation characteristics of G-MSCs. Design. Human G-MSCs (n=5) were isolated and cultured in basic medium (control group), in basic medium with major inflammatory cytokines; 1 ng/ml IL-1β, 10 ng/ml TNF-α, and 100 ng/ml IFN-γ (inflammatory group), in basic medium with 250 μmol/l AA (AA group) and in inflammatory medium supplemented by AA (inflammatory/AA group). All media were renewed three times per week. In stimulated G-MSCs intracellular β-catenin at 1 hour, pluripotency gene expression at 1, 3, and 5 days, as well as colony-forming units (CFUs) ability and cellular proliferation over 14 days were examined. Following a five-days stimulation in the designated groups, multilineage differentiation was assessed via qualitative and quantitative histochemistry as well as mRNA expression. Results. β-Catenin significantly decreased intracellularly in all experimental groups (p=0.002, Friedman). AA group exhibited significantly higher cellular counts on days 3, 6, 7, and 13 (p<0.05) and the highest CFUs at 14 days [median-CFUs (Q25/Q75); 40 (15/50), p=0.043]. Significantly higher Nanog expression was noted in AA group [median gene-copies/PGK1 (Q25/Q75); 0.0006 (0.0002/0.0007), p<0.01, Wilcoxon-signed-rank]. Significant multilineage differentiation abilities, especially into osteogenic and chondrogenic directions, were further evident in the AA group. Conclusions. AA stimulation enhances G-MSCs’ stemness, proliferation, and differentiation properties, effects which are associated with a Wnt/β-catenin signaling pathway activation. Apart from initially boosting cellular metabolism as well as Sox2 and Oct4A pluripotency marker expression, inflammation appeared to attenuate these AA-induced positive effects. Current results reveal that for AA to exert its beneficial effects on G-MSCs’ cellular attributes, it requires to act in an inflammation-free microenvironment.

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Ascorbic Acid/Retinol and/or Inflammatory Stimuli’s Effect on Proliferation/Differentiation Properties and Transcriptomics of Gingival Stem/Progenitor Cells

Cells ◽

10.3390/cells10123310 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3310

Author(s):

Karim M. Fawzy El-Sayed ◽

Amira Bittner ◽

Kristina Schlicht ◽

Mohamed Mekhemar ◽

Kim Enthammer ◽

...

Keyword(s):

Ascorbic Acid ◽

Progenitor Cells ◽

Antigen Processing ◽

Cellular Proliferation ◽

Stem Cell Marker ◽

Basic Medium ◽

Control Group ◽

Differentiation Potential ◽

Mineral Absorption ◽

Mediated Reduction

The present study explored the effects of ascorbic-acid (AA)/retinol and timed inflammation on the stemness, the regenerative potential, and the transcriptomics profile of gingival mesenchymal stem/progenitor cells’ (G-MSCs). STRO-1 (mesenchymal stem cell marker) immuno-magnetically sorted G-MSCs were cultured in basic medium (control group), in basic medium with IL-1β (1 ng/mL), TNF-α (10 ng/mL) and IFN-γ (100 ng/mL, inflammatory-medium), in basic medium with AA (250 µmol/L) and retinol (20 µmol/L) (AA/retinol group) or in inflammatory medium with AA/retinol (inflammatory/AA/retinol group; n = 5/group). The intracellular levels of phosphorylated and total β-Catenin at 1 h, the expression of stemness genes over 7 days, the number of colony-forming units (CFUs) as well as the cellular proliferation aptitude over 14 days, and the G-MSCs’ multilineage differentiation potential were assessed. Next-generation sequencing was undertaken to elaborate on up-/downregulated genes and altered intracellular pathways. G-MSCs demonstrated all mesenchymal stem/progenitor cells characteristics. Controlled inflammation with AA/retinol significantly elevated NANOG (p < 0.05). The AA/retinol-mediated reduction in intracellular phosphorylated β-Catenin was restored through the effect of controlled inflammation (p < 0.05). Cellular proliferation was highest in the AA/retinol group (p < 0.05). AA/retinol counteracted the inflammation-mediated reduction in G-MSCs’ clonogenic ability and CFUs. Amplified chondrogenic differentiation was observed in the inflammatory/AA/retinol group. At 1 and 3 days, the differentially expressed genes were associated with development, proliferation, and migration (FOS, EGR1, SGK1, CXCL5, SIPA1L2, TFPI2, KRATP1-5), survival (EGR1, SGK1, TMEM132A), differentiation and mineral absorption (FOS, EGR1, MT1E, KRTAP1-5, ASNS, PSAT1), inflammation and MHC-II antigen processing (PER1, CTSS, CD74) and intracellular pathway activation (FKBP5, ZNF404). Less as well as more genes were activated the longer the G-MSCs remained in the inflammatory medium or AA/retinol, respectively. Combined, current results point at possibly interesting interactions between controlled inflammation or AA/retinol affecting stemness, proliferation, and differentiation attributes of G-MSCs.

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rhEGF Treatment Improves EGFR Inhibitors-Induced Skin Barrier and Immune Defects

10.21203/rs.3.rs-60830/v1 ◽

2020 ◽

Author(s):

Ji Min Kim ◽

Jun Ho Ji ◽

Young Saing Kim ◽

Suee Lee ◽

Sung Yong Oh ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Egf Receptor ◽

Skin Barrier ◽

Control Group ◽

Ki 67 ◽

Western Blot Assay ◽

Positive Effects ◽

Egfr Expression ◽

Tnf Α ◽

Proliferation And Differentiation

Abstract Background: The mechanisms of epidermal growth factor (EGF) effects EGF receptor inhibitor (EGFRI)-related skin toxicities are as yet unknown. We investigated which mechanisms are involved in EGF’s positive effects. Methods: Two types of EGFRIs, cetuximab and gefitinib, were used to treat the cells or 3d-cultured human skin tissue with recombinant human EGF (rhEGF). The expression levels of skin barrier related proteins, inflammatory cytokines, and antimicrobial peptides (AMPs) were measured by using RT qPCR, ELISA, immunohistochemical (IHC) stain, or immunofluorescence..Results: Using western blot assay, cetuximab decreased EGFR and phosphorylated EGFR (pEGFR) expression. In contrast, rhEGF increased EGFR and pEGFR expression. Also, rhEGF induces EGFR signaling by pAKT and pPI3K expression in gefitinib and rhEGF co-treated cells. Expressions of proliferation and differentiation proteins, both ki-67 and filaggrin, were decreased in EGFRIs -treated tissue. However, in rhEGF and EGFRIs co-treated tissue, those expressions were increased. Pro-inflammatory cytokines, including IL-1α, IL-8, and TNF-α expression, were increased by EGFRIs, and down-regulated by rhEGF. In patients’ tissue evaluation, compared with control, patients’ Ki-67 and EGFR expression were decreased (P=0.015, P=0.001). Patients’ IL-17 and TNF-α expression intensity was higher than that of control group (P=0.038, P=0.037). After treatment with EGF ointment, average values of Ki-67, EGFR, and Melan-A were changed to normal values. Oppositely patients’ proportions of IL-17 and TNF-α were decreased to low stain level.Conclusions: Treatment of rhEGF improved EGFRIs-induced skin eruption via normalizing the proliferation and differentiation of keratinocytes, reducing inflammatory cytokines by the affected EGFRIs.

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Intra-carotid arterial transfusion of circulatory-derived autologous endothelial progenitor cells in rodent after ischemic stroke — evaluating the impact of therapeutic time points on prognostic outcomes

10.21203/rs.2.23279/v2 ◽

2020 ◽

Author(s):

Kun-Chen Lin ◽

Han-Tan Chai ◽

Kuan-Hung Chen ◽

Pei‐Hsun Sung ◽

John Y. Chiang ◽

...

Keyword(s):

Ischemic Stroke ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Optimal Time ◽

Control Group ◽

Endothelial Progenitor ◽

Group 2 ◽

The Impact ◽

Carotid Arterial ◽

Group 1

Abstract Background: This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and Results: Adult-male SD rats (n=70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2x106 cells/by LICA administration 3h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS) and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain-infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2 and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all p<0.0001). By day 60, the endothelial cell markers at protein and cellular levels, and number of small vessels exhibited an opposite pattern of BIV among the groups (all p<0.0001). The protein and cellular levels of inflammation, and protein levels of oxidative stress, autophagy and apoptosis, were highest in group 2, lowest in group 1 and progressively increased from groups 3 to 7 (all p<0.0001). The angiogenesis biomarkers at protein and cellular levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 4 to 7 (all p<0.0001). Conclusion: Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.

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The Impact of Cellular Proliferation on the HIV-1 Reservoir

Viruses ◽

10.3390/v12020127 ◽

2020 ◽

Vol 12 (2) ◽

pp. 127

Author(s):

Maria C. Virgilio ◽

Kathleen L. Collins

Keyword(s):

Cellular Proliferation ◽

Integration Site ◽

Infected Individual ◽

Host Cells ◽

Viral Reservoir ◽

Proliferative Potential ◽

Proliferation And Differentiation ◽

Latently Infected ◽

Infected Cells ◽

The Impact

Human immunodeficiency virus (HIV) is a chronic infection that destroys the immune system in infected individuals. Although antiretroviral therapy is effective at preventing infection of new cells, it is not curative. The inability to clear infection is due to the presence of a rare, but long-lasting latent cellular reservoir. These cells harboring silent integrated proviral genomes have the potential to become activated at any moment, making therapy necessary for life. Latently-infected cells can also proliferate and expand the viral reservoir through several methods including homeostatic proliferation and differentiation. The chromosomal location of HIV proviruses within cells influences the survival and proliferative potential of host cells. Proliferating, latently-infected cells can harbor proviruses that are both replication-competent and defective. Replication-competent proviral genomes contribute to viral rebound in an infected individual. The majority of available techniques can only assess the integration site or the proviral genome, but not both, preventing reliable evaluation of HIV reservoirs.

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The Impact of the Virtual Laboratory on Students’ Attitude in a General Physics Laboratory

International Journal of Online Engineering (iJOE) ◽

10.3991/ijoe.v13i04.6811 ◽

2017 ◽

Vol 13 (04) ◽

pp. 20 ◽

Cited By ~ 6

Author(s):

Gülsüm Aşıksoy ◽

Didem Islek

Keyword(s):

Attitude Scale ◽

Virtual Laboratory ◽

Control Group ◽

Structured Interviews ◽

Control Group Design ◽

Physics Laboratory ◽

Positive Effects ◽

Students Attitudes ◽

Laboratory Experiences ◽

The Impact

Abstract: The purpose of this study is to investigate the impact of virtual laboratory experiences in physics laboratory attitudes of students. It also aims to determine the views of students’ on virtual laboratory. The study involved 42 students who was divided into two groups (21 experimental, 21 control). Students were randomly assigned to both groups. In the research, the pre-test and post-test control group design was used. The experimental group used the virtual laboratory. On the other hand the control group used physical laboratory. The research data were obtained via the “physics laboratory attitude scale” and semi-structured interviews. The result of this study carried out that virtual laboratory experiences made positive effects on students’ attitudes. In addition, semi-structured interviews were found out that they had positive opinions regarding the virtual physics laboratory experiences.

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rhEGF Treatment Improves EGFR Inhibitor-Induced Skin Barrier and Immune Defects

Cancers ◽

10.3390/cancers12113120 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3120

Author(s):

Ji Min Kim ◽

Jun Ho Ji ◽

Young Saing Kim ◽

Suee Lee ◽

Sung Yong Oh ◽

...

Keyword(s):

Egf Receptor ◽

Skin Barrier ◽

Control Group ◽

Ki 67 ◽

Positive Effects ◽

Egfr Expression ◽

Tnf Α ◽

Proliferation And Differentiation ◽

Gefitinib Treatment ◽

Immune Defects

The mechanisms of epidermal growth factor (EGF) affecting EGF receptor inhibitor (EGFRI)-related skin toxicities are as yet unknown. We investigated which mechanisms are involved in EGF’s positive effects. Two types of EGFRIs, cetuximab and gefitinib, were used to treat the cells or 3d-cultured human skin tissue with recombinant human EGF (rhEGF). As a result, rhEGF increased EGFR and pEGFR expression. Furthermore, rhEGF induces EGFR signaling by pAKT and pPI3K expression in gefitinib and rhEGF co-treated cells. In addition, rhEGF bound to EGFR after than cetuximab, but cetuximab bound to EGFR more strongly than rhEGF. Moreover, expressions of proliferation and differentiation proteins, both ki-67 and filaggrin, were decreased in EGFRI-treated tissue. However, in rhEGF and EGFRI co-treated tissue, those expressions were increased. Expression of IL-1α, IL-8, and TNF-α was increased by EGFRIs and down-regulated by rhEGF. Furthermore, hBD-2 and hBD-3 protein expressions were inhibited by cetuximab or gefitinib treatment, and those decrements were increased by rhEGF treatment. In patients’ tissue evaluation, compared with controls, patients’ Ki-67 and EGFR expression were decreased (p = 0.015, p = 0.001). Patients’ IL-17 and TNF-α expression intensity was higher than that of the control group (p = 0.038, p = 0.037). After treatment with EGF ointment, average values of Ki-67, EGFR, and Melan-A were changed to normal values. Oppositely, patients’ proportions of IL-17 and TNF-α were decreased to low stain level. In conclusion, treatment of rhEGF improved EGFRI-induced skin eruption via normalizing the proliferation and differentiation of keratinocytes, reducing inflammatory cytokines by the affected EGFRIs.

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The Health Effects of Worksite HIV/AIDS Interventions: A Review of the Research Literature

American Journal of Health Promotion ◽

10.4278/0890-1171-11.2.150 ◽

1996 ◽

Vol 11 (2) ◽

pp. 150-157 ◽

Cited By ~ 8

Author(s):

Mark G. Wilson ◽

Cynthia Jorgensen ◽

Galen Cole

Keyword(s):

Health Effects ◽

Organizational Factors ◽

Research Literature ◽

Future Research ◽

Control Group ◽

Search Methods ◽

Positive Effects ◽

Introductory Article ◽

The Impact ◽

Hiv Aids

Purpose. To examine the individual and organizational health effects of HIV/AIDS interventions conducted at the worksite. Search Methods. This review is part of a series of reviews that used search methods described in an introductory article. To supplement these methods, HIV/AIDS-specific periodicals were searched to include journals that might not be incorporated in the computerized databases. Twelve of the 20 articles identified through the Centers for Disease Control and Prevention and our own subsequent searches met the criteria and were included in this review. Findings. Ten of the 12 studies reviewed reported positive effects of employee education programs on knowledge or attitudes. Nine of the studies involved health care workers or employees with potential occupational exposure to HIV, and nine lacked a comparison or control group. None of the studies however, examined the effects of policies, manager training, or family education on the organization or person. Conclusions. Methodologic weaknesses in many of the studies reviewed, coupled with the small number of studies, led us to conclude that the research literature on worksite HIV/AIDS interventions is weak. Impact is, however, plausible. Future research should be directed toward developing valid measures of key variables, controlling for confounding factors, and ultimately examining the impact of organizational factors.

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The Effect of Ascorbic Acid on Interleukin-10 and Tumor Necrosis Factor-α Cytokines in Rattus norvegicus with Endometritis

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2021.6946 ◽

2021 ◽

Vol 9 (A) ◽

pp. 798-801

Author(s):

Muhammad Oky Prabudi ◽

M. F. G. Siregar ◽

I. P. A. Nasution ◽

S. Ilyas

Keyword(s):

Ascorbic Acid ◽

Treatment Group ◽

Inflammatory Cytokines ◽

Rattus Norvegicus ◽

Tumor Necrosis ◽

Mean Value ◽

Negative Control ◽

Control Group ◽

Tnf Α ◽

Necrosis Factor

BACKGROUND: Endometritis is a gynecological disease characterized by inflammation of the endometrial glands and stroma. Inflammatory stimuli or tissue injury induce inflammatory pain through the release of cytokines. Ascorbic acid (AA) is a water-soluble Vitamin that plays a role in inhibiting the production of proinflammatory cytokines and increases the expression of anti-inflammatory cytokines. AIM: The purpose of this study was to find out the association between administration of AA and inflammatory cytokines in experimental animals Rattus norvegicus with endometritis. METHODS: The research was conducted using virgin female R. norvegicus laboratory mice weighing 250–300 g and aged 11–12 weeks with an estrus cycle of 5–6 days. Mice with regular oestrous cycles were randomly divided into three groups: group 1 was given 200 L of water orally without Escherichia coli inoculation and represented a negative control. Groups 2 and 3 were inoculated (50 L/rat) E. coli intravaginally, 106 colony-forming unit/mL, Group 2 was not given AA and the other side Group 3 was assigned AA. The interleukin (IL)-10 and tumor necrosis factor (TNF)-α _cytokines examination was carried out by histopathological examination through a biopsy of the endometrial tissue. Hypothesis testing on the data was analyzed by the Kruskal Wallis test using Statistical Package for Social Sciences. RESULTS: Data from the current study revealed that the highest mean value of IL-10 was found in the negative control group (2.5) and the lowest value in the positive control group (1.3). Regarding TNF-α _the highest mean value (2.8) was found in the treatment group and the lowest mean value (2.1) was found in the treatment group. Using the Kruskal Wallis test, IL-10 and TNF-α _showed insignificant results (p = value 0.304 and 0.145 respectively). CONCLUSIONS: The administration of AA did not affect the decrease in TNF-α _or the upregulation of IL-10 as anti-inflammatory cytokines.

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Mindfulness Enhances Cognitive Functioning: A Meta-Analysis of 95 Randomized Controlled Trials

10.31234/osf.io/vzxw7 ◽

2020 ◽

Author(s):

Nur Hani Hani Zainal ◽

Michelle G. Newman

Keyword(s):

Randomized Controlled Trials ◽

Sustained Attention ◽

Treatment Effects ◽

Control Group ◽

Controlled Trials ◽

Cognitive Domains ◽

Positive Effects ◽

Mindfulness Skills ◽

Randomized Controlled ◽

The Impact

Background: The past 30 years have witnessed growing scientific interest regarding the impact of mindfulness-based interventions (MBIs) on cognitive functions. Several theories propose that habitually exercising mindfulness skills can improve cognitive abilities, but no comprehensive quantitative reviews of the effect of MBIs on global and unique cognitive domains exist to date. Method: This systematic review thus examined the effects of MBI on global cognitive ability (GCA) and 16 specific cognitive domains. MBI randomized controlled trials (RCTs) that administered cognitive tests pre- and post-treatment were included. Open-trials, non-randomized MBIs, and case-control studies were excluded. Keywords included “mindful*,” AND “executive attention (EA),” OR “working memory (WM).” Robust variance estimation and moderator analyses were conducted. Results: Ninety-five RCTs (n = 7,408) met eligibility criteria. MBI (vs. waitlist or no-treatment) had small-to-moderate significant effects on GCA, WM accuracy, inhibition accuracy and latency, EA, sustained attention accuracy, processing speed, and subjective attentional control (SAC) (g = 0.24 – 0.52). Likewise, MBI (vs. active control) had small-to-moderate positive effects on GCA, orienting, EA, WM accuracy, sustained attention (indexed by intra-individual coefficient of variation), and SAC (average g = 0.17 – 0.41). Age, gender, study quality, treatment duration, publication year, retention, statistical analysis, and country, moderated some treatment effects. Publication bias analyses showed that reliable treatment effects were restricted to EA, WM accuracy, inhibition accuracy, sustained attention, and SAC, depending on the control group. Conclusion: MBIs confer notable neuropsychological benefits and dose-response effects on some specific (vs. global) cognitive domains. Limitations, theoretical, and applied implications are discussed. (NOTE: This paper has not been peer reviewed. Please do not copy or cite without author's permission.)

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Enhancing metacognition through thinking instruction: A case study in a Taiwanese university

Journal of University Teaching and Learning Practice ◽

10.53761/1.17.5.16 ◽

2020 ◽

Vol 17 (5) ◽

pp. 241-270

Author(s):

Mei-Hui Chen ◽

Keyword(s):

Thinking Skills ◽

Medium Size ◽

Control Group ◽

Control Group Design ◽

Personal Lives ◽

Thinking Dispositions ◽

Positive Effects ◽

English Classes ◽

The Impact

This study investigated the impact of thinking instruction on students’ metacognition and thinking behavior. Higher-order thinking occurs when individuals use their underlying metacognitive strategies which increase the probability of achieving a desirable result. The study was designed as a case study of an intervention and a posttest-only control group design was adopted. Participants consisted of students with a variety of majors were recruited from a medium-size university located in southern Taiwan. Two classes of the Developing Thinking course, totaling 78 students, comprised the group receiving the intervention, while 196 students in six General English classes comprised the comparison group. The intervention students were introduced to thinking skills, facts and opinions, question stems, and thinking from different perspectives. The quantitative results show strong evidence that the thinking instruction exerts statistically significant positive effects on students’ metacognition. Qualitative evidence also shows improvements in cognitive awareness with students demonstrating a more consistent application of thinking skills, an increased ability to think critically with thinking dispositions cultivated, and most importantly, a transfer of thinking behavior across the curriculum and in their personal lives. The researcher suggests the value of introducing thinking instruction to promote critical thinkers.

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