| 1. |
- Alizadehgharib, Sara, et al.
(författare)
-
Effects of the methacrylate/acrylate monomers HEMA, TEGDMA, DEGDA, and EMA on the immune system
- 2017
-
Ingår i: Clinical and Experimental Dental Research. - : Wiley. - 2057-4347. ; 3:6, s. 227-234
-
Tidskriftsartikel (refereegranskat)abstract
- Incomplete curing of dental fillings may lead to leakage of methacrylate/acrylate monomers, which may come in contact with different cells of the immune system in oral tissues. Very little is known about the different immunologic effects caused by these methacrylates/acrylates. The objective of the present study was to study if and how the methacrylate/acrylate monomers ethyl methacrylate (EMA) and diethylene glycol diacrylate (DEGDA) affect the immune system in vivo and in vitro in comparison to 2-hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA). Human peripheral blood mononuclear cells were exposed to the different monomers (500 and 1000 μM) for 24 hr in vitro. BioPlex Pro™ assays were used for cytokine analysis. In vivo, BALB/c mice were immunized subcutaneously at the base of the tail with HEMA, TEGDMA, EMA, or DEGDA in combination with ovalbumin (OVA) in order to study adjuvant properties of the 4 monomers. Peripheral blood mononuclear cells exposed to DEGDA had viability less than 50% of the cells. A pattern was observed where the levels of most cytokines were elevated after exposure to HEMA or TEGDMA. Since that, many cells died after DEGDA-exposure, the only observed cytokine secretion was a significantly increased production of interleukin-18. In the in vivo experiments, all mice immunized with DEGDA died after the booster injection. Mice receiving OVA in combination with HEMA, TEGDMA, or EMA developed a higher immunoglobulin G anti-OVA antibody levels compared to the group immunized with OVA alone. We could not demonstrate any significant difference in antibody levels among the mice receiving the various methacrylate/acrylate monomers. The different monomers affected the production, increase and decrease, of different cytokines in vitro but resulted also in vivo in increased antibody production and T-cell activity.
|
|
| 2. |
- Alizadehgharib, Sara, et al.
(författare)
-
Immunological response of human leucocytes after exposure to lipopolysaccharides from Porphyromonas gingivalis.
- 2021
-
Ingår i: Clinical and experimental dental research. - : Wiley. - 2057-4347. ; 7:4, s. 531-538
-
Tidskriftsartikel (refereegranskat)abstract
- Porphyromonas gingivalis (P. gingivalis) is a gram-negative bacterium and an important etiologic agent of periodontitis. P. gingivalis releases outer membrane vesicles containing lipopolysaccharides (LPS), which can penetrate periodontal tissues. Once in the periodontal tissues and in contact with immune cells, it may participate in the destructive innate host response associated with the disease. The exact mechanism of P. gingivalis LPS in the disease process is not clear, but it is known to affect a variety of immune responses.To investigate how LPS from P. gingivalis affect neutrophil extracellular trap (NET) formation, cell death and production of cytokines from human neutrophils and peripheral mononuclear blood mononuclear cells (PBMCs).Isolated neutrophils and PBMCs were cultured with LPS from P. gingivalis or Escherichia coli (E. coli) (control). The NET formation was measured using Sytox green stain. Cell death of neutrophils and PBMCs was analyzed using flow cytometry or Sytox green stain. Cytokine production was measured using enzyme-linked immunosorbent assay (ELISA) kit or Bio-Plex assay.Exposure to LPS from P. gingivalis and E. coli caused significantly lower cell death in neutrophils. NETs were formed after exposure to the two different LPS. In PBMCs, exposure to P. gingivalis and E. coli LPS caused increased levels of IL-1β and IL-6 compared to unstimulated controls. Increased cell death in PBMCs after exposure to LPS from E. coli in comparison to LPS from P. gingivalis and unstimulated controls was also observed.LPS from P. gingivalis has the ability to affect both human neutrophils and PBMCs with regard to cytokine production, cell death and production of NETs. LPS from P. gingivalis could be involved in the pathogenesis of periodontitis, and our results may contribute information regarding possible markers for diagnosis and targets for treatment of periodontal disease.
|
|
| 3. |
- Alizadehgharib, Sara, et al.
(författare)
-
The effect of a non-tobacco-based nicotine pouch on mucosal lesions caused by Swedish smokeless tobacco (snus)
- 2022
-
Ingår i: European Journal of Oral Sciences. - : Wiley. - 0909-8836 .- 1600-0722. ; 130:4
-
Tidskriftsartikel (refereegranskat)abstract
- Oral mucosal lesions are commonly found in Swedish smokeless tobacco (snus) users where the pouch is placed. These lesions are reversible, that is, clinical and histological tissue changes return to normal following cessation. However, the exact mechanisms behind these changes are unknown. The main aim of this study was to investigate how snus-like non-tobacco-based nicotine pouches affect the oral mucosa and the severity of pre-existing lesions. Sixty regular users of Swedish smokeless tobacco were encouraged to substitute their snus with non-tobacco-based nicotine pouch products during a 6-week period. Meanwhile, oral mucosal lesions were assessed using a four-degree scale. Over time, a reduction of pre-existing mucosal lesions was observed between baseline and the final visit. In a second part, the effect of exposure to regular snus on the production of 48 different cytokines in peripheral blood mononuclear cells was compared in vitro with that resulting from exposure to the non-tobacco-based nicotine products. Results showed significantly increased production of proinflammatory cytokines in cells exposed to regular snus compared to untreated or cells exposed to the non-tobacco-based nicotine products. This may be related to the improved clinical appearance of the oral mucosa in the participants that used the non-tobacco-based nicotine test pouches.
|
|
| 4. |
- Alizadehgharib, Sara, et al.
(författare)
-
The effects of the dental methacrylates TEGDMA, Bis-GMA, and UDMA on neutrophils in vitro.
- 2020
-
Ingår i: Clinical and experimental dental research. - : Wiley. - 2057-4347. ; 6:4, s. 439-447
-
Tidskriftsartikel (refereegranskat)abstract
- The prevalent usage of methacrylates in modern dentistry demands good knowledge of their biological impacts. While there have been several studies demonstrating the effects of different methacrylic monomers on mononuclear white blood cells, very little is known about the effects caused by these monomers on neutrophilic granulocytes. The objective of this study was to add novel knowledge about how neutrophils are affected by exposure to triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), and bisphenol A glycol dimethacrylate (Bis-GMA) alone or in combinations.Isolated neutrophils were cultured in the presence or absence of methacrylates. The IL-8 release was measured using a DuoSet ELISA development kit. Apoptosis and necrosis were analyzed using flow cytometry. The formation of neutrophil extracellular traps (NETs) was investigated using Sytox green DNA staining combined with microscopically examination of released DNA and myeloperoxidase (MPO).The release of IL-8 was significantly increased after exposure to TEGDMA, Bis-GMA, UDMA, or TEGDMA in combination with Bis-GMA or UDMA compared to the unstimulated controls. Exposure to TEGDMA, UDMA, and Bis-GMA for 24hr separately or in combination did not affect apoptosis or necrosis of the exposed neutrophils. NET structures were formed by neutrophils after exposure to the different combinations of the methacrylates.The combination of TEGDMA and Bis-GMA had a synergistic proinflammatory effect on neutrophils by increasing the release of IL-8 and the formation of NET structures. The changes in the normal functions of neutrophils caused by methacrylate exposure may lead to altered inflammatory response and relate to previously reported adverse immune reactions caused by these substances.
|
|
| 5. |
- Alizadehgharib, Sara, et al.
(författare)
-
The Immunomodulatory Properties of 2-Hydroxyethyl Methacrylate are Mediated by the NLRP3 Inflammasome.
- 2018
-
Ingår i: The journal of adhesive dentistry. - 1461-5185. ; 20:3, s. 213-220
-
Tidskriftsartikel (refereegranskat)abstract
- The methacrylate monomer 2-hydroxyethyl methacrylate (HEMA), commonly used in dentistry, has multiple effects on the immune system. This study examined whether HEMA affects the immune system by inducing formation of the NLRP3 inflammasome.Human peripheral blood mononuclear cells (PBMCs) and the human monocyte cell line THP1 were cultured with or without 1000 μM HEMA. To block NLRP3 inflammasome activation, 130 mM KCl was also added to some of the cultures. For the in vivo studies, two different experimental setups were used. In the first experimental setup, mice were injected subcutaneously at the base of the tail with 20 μmol HEMA with or without 100 mM KCl. After 3 weeks, the animals were given an identical booster injection. Two weeks after the last injection, the mice were sacrificed and splenectomized. In the second experimental setup, HEMA (20 μmol), with or without 100 mM KCl, was injected subcutaneously into the tails of BALB/c mice. The mice were given two similar injections at 3-week intervals to allow evaluation of the local inflammation induced by HEMA. After the last inoculation, the injection site was examined daily for 4 days, after which the mice were sacrificed.Cultures of PBMCs and THP1 cells exposed to HEMA in vitro produced more IL-1ß and IL-18 than did control cells. Increased extracellular concentration of KCl inhibited the secretion of IL-1ß. HEMA exposure did not induce cytokine production in variants of the THP1 cell line unable to form the NLRP3 inflammasome. For the first experimental setup, the level of unstimulated basic splenocyte proliferation in vitro was significantly higher in cultures from mice exposed in vivo to HEMA only than in cultures from mice injected with HEMA plus KCl. In the second experimental setup of the in vivo studies, the HEMA-treated mice developed more pronounced inflammation at the site of injection compared to the group of mice given HEMA plus KCl.HEMA affects the immune system by inducing formation of the NLRP3 inflammasome.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Backström, Ellenor, 1980-, et al.
(författare)
-
Regulation of Adenovirus Late Region 1 Splicing
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The major late transcription unit (MLTU) produces one pre-mRNA that is processed into more than 20 cytoplasmic mRNAs by alternative polyadenylation and extensive alternative 3' splice site usage. The alternative splicing of the MLTU is temporally regulated, resulting in the expression of only one mRNA, the L1 52,55K, before the onset of viral genome replication. The L1 unit also encodes the IIIa mRNA, the expression of which is highly regulated at the level of splicing. We have previously shown that the adenoviral L4-33K protein enhances IIIa splicing via the IIIa virus infection-dependent splicing enhancer element. In this study we show that serine to glycine mutations in the tiny RS domain of the L4-33K protein retain more activity in vivo compared to results obtained previously in vitro. In addition, it is also clear that these mutations in the RS domain affect the sub-cellular localization of L4-33K. Thus, the RS domain appears to contain a nuclear localisation signal that is dependent on the serine residues. In a previous report we showed that, in extracts prepared from adenovirus-infected cells, splicing is independent of the general splicing factor U2AF. In this study we also demonstrate that none of the tested U2AF-replacement candidate proteins (PUF60, Caper α, and Caper β) collaborate with L4-33K in the activation of IIIa splicing. It has been suggested that regulation of L1 alternative splicing does not require cis-competition between the 52.55K and IIIa 3' splice sites. We find that activity of the IIIa splice site increases considerably in the absence of cis-competition with the 52,55K splice site. Interestingly, this cis-competition is not virus-specific since this observation is reproducible in a transcription unit where the β-globin 3' splice site replaces the natural 52,55K 3' splice site. We conclude that L1 alternative splicing conforms to the general rule in that it ordinarily makes use of the proximal 3' splice site (52,55K), whereas activation of distal 3' splice site usage requires active intervention. In adenovirus this intervention is achieved by production of the L4-33K protein.
|
|
| 9. |
- Brolin Låftman, Sara, 1974-, et al.
(författare)
-
Bullying experiences before and after the transition from lower to upper secondary school : associations with subsequent mental health in a Swedish cohort
- 2024
-
Ingår i: BMC Public Health. - 1471-2458. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Previous research has shown that exposure to bullying is linked to long-term adverse mental health consequences. However, prospective studies examining the persistence of bullying, using information from repeated time points, are limited. The aim of this study was to examine, firstly, the extent to which exposure to bullying among adolescents in Sweden changes between grades 9 (age 15-16) and 11 (age 17-18) (i.e., before and after the transition from lower to upper secondary school); secondly, whether being bullied in grade 9 or 11 is associated with depression and anxiety symptoms at age 20-21; and thirdly, if being bullied in both grade 9 and 11 is linked to an even higher likelihood of subsequent depression and anxiety symptoms. Potential differences by gender were investigated throughout.Methods: Data was derived from the Swedish cohort study Futura01 involving individuals attending grade 9 in the school year 2016/17 (n = 2323). We utilised self-reported information from three survey waves conducted in 2017, 2019, and 2022, and linked registry information on sociodemographic characteristics. Bullying was assessed using a single item in waves 1 and 2. Depression and anxiety symptoms were measured using the Patient Health Questionnaire-4 (PHQ-4) in wave 3. Gender stratified binary logistic regressions were performed.Results: Among those who were bullied in grade 9, 22.6% of males and 35.8% of females continued to experience bullying in grade 11. For females, exposure to bullying in grade 9 or 11 was associated with an increased likelihood of reporting depression and anxiety symptoms at age 20-21, with the highest odds for those bullied at both time points. For males, only one statistically significant association was identified - specifically, between being bullied in grade 9 and subsequent depression symptoms.ConclusionsFor a majority of adolescents who experience bullying in lower secondary school, but not all, the transition to upper secondary school proves to be beneficial as the bullying typically does not persist. However, bullying can have long-term health effects, in particular for females. These findings emphasise the importance of effective measures to address bullying within schools.
|
|
| 10. |
- Brolin Låftman, Sara, 1974-
(författare)
-
Children's Living Conditions : Studies on Health, Family and School
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present dissertation includes four empirical studies, each of which focuses on specific aspects of children’s living conditions. Study I analyses the association between young people’s social relations and health complaints using Swedish nationally representative survey data on 10- to 18-year-olds. Both relations with parents and with peers are associated with health complaints. Relational content is more strongly associated with health complaints than is relational structure. With regard to relational content, strained relations are more strongly associated with health complaints than are supportive relations. Study II investigates how effort and reward in school are associated with pupils’ subjective health using data from the Stockholm School Survey. Both effort and reward are shown to be positively associated with subjective health, and in particular pupils who report to put in high effort in school have high levels of subjective health. Contextual variation in health is found for girls but not for boys. Study III is based on Swedish register data and analyses the association between family type and choice of programme in upper secondary school. Children in single-mother households less often choose the natural science/technology (NT) programme compared with children who live with two original parents. Having a resident or a non-resident parent with NT skills is positively associated with choice of the NT programme. Study IV analyses the association between family type and social support, health, and material resources in 24 countries. The data are derived from the international Health Behaviour of School-aged Children (HBSC) survey. In a majority of the countries studied, children in single-mother households report smaller resources compared with children living with two original parents. No clear pattern is found with regard to differences between countries.
|
|
