Browsing by Subject "inflammation"
Now showing items 1-10 of 10
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(2016)Goals. Inflammation has been found to be associated with psychological symptoms. Especially in regard to depression, there is broad evidence that depressed people have higher levels of inflammation. Higher inflammation has also been linked to poorer response to SSRI-medication. Anxiety has been found to have stronger association to experienced pain than depression and in earlier studies references to an independent association between anxiety and inflammation has emerged. The purpose of this study was to explore if a connection between anxiety and inflammation can be found and what factors are possibly contributing to that connection. Goal was to find factors that can help maintain and improve individual's quality of life and ability to work. Methods. Data used in this study belonged to the biomarker project (project 4), which was part of the second stage of the Midlife in the United States (MIDUS) longitudinal study. The mean age of participants was 57.32 (sd. 11.55) years. As a measure of inflammation serum levels of cytokine interleukin-6 (IL-6) were collected from the blood of participants. Anxiety was measured by Spielberger Trait Anxiety Inventory (STAI). The association between anxiety and inflammation was explored by a linear regression analysis. Sociodemographic factors and also a broad range of other factors related to inflammation and anxiety were controlled in the models. In addition the possible moderating role of inner self-control was studied by a hierarchical linear regression analysis. The sub factor cognition control of the self-control scale was used as a measure of inner self-control. Results and conclusions. When inflammation was predicted only by anxiety, anxiety was a statistically significant predictor and this association remained significant after sociodemographic factors were controlled. When broad range of other controlled variables was included in the model a connection between anxiety and inflammation could not be found. It seems that the association between anxiety and inflammation is mainly due to other factors. Especially the amount of chronic conditions attenuated the association. Inner self-control did not have a statistically significant effect to the connection between anxiety and inflammation. The best predictor for inflammation in this study was body mass index and also other health behavior related factors had a significant role. In regard to the wellbeing of an individual and individual's ability to work, weight control and healthy lifestyle choices are crucial.
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(2020)An increased attention has been drawn towards porous silicon (PSi) based materials for biomedical applications, due to their promising features demonstrated through several scientific studies. Here, we further investigated the biological responses of PSi nanoparticles (NPs) with different surface chemistries, including immunomodulatory effects, inflammation mitigation and biocompatibility. In this collaborative study, the PSi NPs were investigated both in vitro and in vivo, using different molecular biology and biochemistry techniques, e.g., qPCR, ELISA, cell sorting and cell viability assays. Our results showed the capabilities of these PSi NPs to relieve the inflammatory conditions, whereas significant decrease was recorded of pro-inflammatory cytokines: TNF-α, IL-1β and IL-6. Likewise, these PSi NPs revealed a considerable consumption aptitude of pro-inflammatory reactive oxygen species molecules. Administrating PSi NPs in an acute liver inflammation (ALI) model, showed no conspicuous influence on cellular viability. Thus, the outcome of this study demonstrates the potential biocompatibility of PSi nanomaterials, in addition to their outstanding features as potential candidates for further incorporating in ALI applications.
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(2020)An increased attention has been drawn towards porous silicon (PSi) based materials for biomedical applications, due to their promising features demonstrated through several scientific studies. Here, we further investigated the biological responses of PSi nanoparticles (NPs) with different surface chemistries, including immunomodulatory effects, inflammation mitigation and biocompatibility. In this collaborative study, the PSi NPs were investigated both in vitro and in vivo, using different molecular biology and biochemistry techniques, e.g., qPCR, ELISA, cell sorting and cell viability assays. Our results showed the capabilities of these PSi NPs to relieve the inflammatory conditions, whereas significant decrease was recorded of pro-inflammatory cytokines: TNF-α, IL-1β and IL-6. Likewise, these PSi NPs revealed a considerable consumption aptitude of pro-inflammatory reactive oxygen species molecules. Administrating PSi NPs in an acute liver inflammation (ALI) model, showed no conspicuous influence on cellular viability. Thus, the outcome of this study demonstrates the potential biocompatibility of PSi nanomaterials, in addition to their outstanding features as potential candidates for further incorporating in ALI applications.
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(2017)Cortical stroke induces a chain of events that results in secondary injury in the ipsilateral thalamus. Inflammation is a key player in the delayed injury. Microglia, the resident innate immune cells of the brain, seem to have an important role in the initiation and maintenance of the inflammation. After infarct they are rapidly activated and start to proliferate and release proinflammatory cytokines. They may even phagocytose viable neurons, a phenomenon called "phagoptosis". Many studies, which have aimed at inhibition of the the detrimental function of microglia, suggest that inhibition of microglia might offer promising therapeutical targets. However, microglia are also involved in the resolution and the repair phase after infarct, which makes development of novel therapies challenging. The only approved treatment for ischemic stroke, a fibrinolytic agent, has a very narrow therapeutic time window. Thus, new treatments are urgently needed. Modulation of inflammation may offer a wider therapeutic time window. In this study, we investigated the effects of two potentially neurotrophic factors, CDNF (cerebral dopamine neurotrophic factor) and MANF (mesencephalic astrocyte-derived neurotrophic factor), as well as a specific vitronectin receptor blocker, cRGDfV, on the prevention of neuronal death in thalamus in a transient murine cortical stroke model. MANF and CDNF are proteins released during stress of the endoplasmic reticulum (ER). They have been shown to protect neurons during ER stress and to reduce the production of some proinflammatory mediators. The vitronectin receptor blocker has in vitro inhibited microglial phagoptosis. The treatments were administered as single injections to the thalamus 7 days after the stroke onset. CDNF and MANF alleviated functional deficits, but did not protect thalamic neurons from death or affect the accumulation of phagocytic microglia. cRGDfV neither enhanced functional outcome nor protected neurons from death. The mechanisms of action were not investigated. In addition, we investigated, whether the death of thalamic neurons in the cortical stroke results in sensitization to pain. Central post-stroke pain has been reported on stroke patients and it has been associated with the death or the disturbances in the function of thalamic neurons. However, in spite of significant reduction in the number of neurons in the ipsilateral thalamus and the increase in the accumulation of phagocytic microglia on day 30 after stroke, we did not observe any significant sensitization to pain caused by thermal or mechanical stimuli on days 3, 14 and 28 after stroke. In conclusion, transient ischemic cortical stroke doesn't seem to induce sensitization to pain. MANF and CDNF seem to alleviate functional deficiencies, but they do not protect thalamic neurons from delayed death.
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(2019)Kronisk skleroserande sialadenit (KSS) anses vara en manifestation av IgG4-associerad sjukdom (IgG4-AS). Kohorter i tidigare publikationer är små och omfattar sällan västerländsk befolkning. KSS kliniska beteende samt behovet av uppföljning i denna patientpopulation bör studeras. Studiens mål var att utreda ifall KSS alltid är en manifestation av IgG4-AS eller förknippas med andra autoimmuna sjukdomar, samt att utreda vilka ytterligare undersökningar denna patientpopulation kräver. Materialet bestod av patienter som mellan åren 2000 - 2017 inom HUCS sjukvårdsdistrikt fått diagnosen KSS efter submandibulektomi (n=51). Vi omvärderade patienternas histologiska vävnadsprover och utförde immunohistokemisk färgning för IgG4. IgG4 positiva vävnadsprover (≥70 IgG4-positiva plasmaceller/ high power field (HPF)) färgades för IgG och CD31. Diagnosen IgG4-AS tillskrevs ifall ‘Boston consensus statement’- kriterierna för IgG4-AS uppfylldes. Vi granskade patientjournaler och skickade en uppföljningsblankett angående symptom av IgG4-AS eller autoimmuna sjukdomar. Trettiofyra vävnadsprover uppfyllde kriterierna för KSS, 17 vävnadsprover tillskrevs diagnosen icke-skleroserande kronisk sialadenit (KS). I 19 fall associerades en spottkörtelsten till organskadan. Tolv vävnadsprover var IgG4-positiva, varav två uppfyllde kriterierna för IgG4-AS. Båda fallen tillhörde KS-gruppen och hade manifestationer av IgG4-AS i andra organ. Histopatologiska drag hos KSS och KS sammanföll delvis. I finländsk befolkning verkar KSS inte tillhöra IgG4-AS. Däremot kan KS vara associerat med IgG4-AS. Att histologiskt urskilja KSS från KS är utmanande. Således bör IgG4-färgning utföras när lymfoplasmacytära infiltrat påträffas i KS och KSS.
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(2021)The immune system is crucial in the central nervous system (CNS), protecting sensitive tissues, promoting regeneration, and maintaining homeostasis. It is involved in CNS-disorders, such as neurodegenerative diseases and neurological insults related to stroke. Critical myeloid leukocytes in the CNS are microglia, divided into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. This polarization achieves modulation of the inflammatory response by amplifying or dampening it. Therefore, microglia are widely investigated in CNS-disorders. β2-integrins are adhesion proteins that mediate inflammation. They are expressed explicitly on leukocytes, including microglia. Important processes, such as phagocytosis and cell motility, are regulated by β2-integrins. They also relay downstream signals, altering inflammation in many settings, although their effects on microglial properties and stroke are currently poorly understood. We here aimed to investigate the role of β2-integrins in stroke-related injury and microglia polarization in vivo using knock-in (KI) mice, which lack functional β2-integrins. Our results show that in a mouse model of haemorrhagic stroke, the functional outcome was less severe in β2-integrin KI versus wild-type (WT) mice (P = 0.0147), suggesting that β2-integrins are involved in stroke pathophysiology. Furthermore, by using flow cytometry we observed significantly lower frequencies of M1 microglia in the KI mouse brain (P = 0.0096). Therefore, our findings reveal neuroprotective aspects by inhibiting β2-integrins in neuroinflammation. Investigating microglial properties mediated by β2-integrins could contribute to the understanding of neuroinflammatory events, leading to the development of therapies for poorly treated CNS-disorders. Our results suggest that β2-integrins should be further explored as molecular targets for novel stroke treatments.
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(2019)Background: Despite the well-established link between diabetes and dementia risk, the impact of prediabetes and diabetes on the prodromal dementia phase remains controversial. In this study, we investigated whether prediabetes and diabetes increase the risk of cognitive impairment–no dementia (CIND) and accelerate its progression to dementia, as well as the possible underlying mechanisms. Methods: In the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), one cohort of cognitively-intact individuals (n=1,837) and one cohort of individuals with CIND (n=671) aged ≥60 years were followed for up to 15 years. At baseline and each follow-up (every 3 or 6 years), a neuropsychological test battery was administered, and the domains of episodic memory, processing speed, executive function, visuospatial abilities, and language were derived. CIND was defined as having no dementia and cognitive performance ≤1.5 SDs below age group-specific means in at least one cognitive domain. Dementia was diagnosed according to DSM-IV criteria. Diabetes (controlled and poorly-controlled) was diagnosed by physicians through medical assessment, clinical records, and glycated hemoglobin (HbA1c) ≥6.5%. Prediabetes was identified as HbA1c 5.7-6.4% in diabetes-free participants. Clinicians diagnosed heart disease and collected blood samples used to measure C-reactive protein (CRP). Data were analyzed with Cox regression models adjusted for possible confounders. Results: At baseline, in the cognitively-intact cohort, 133 (7%) participants had diabetes and 615 (34%) had prediabetes. During follow-up (mean 9.2 ± 3.0 years [range=2.2-15.5 years]), 544 (30%) individuals in the cognitively-intact cohort developed CIND. Poorly-controlled diabetes (HbA1c ≥7.5%) was associated with 2-times higher risk of CIND (HR 2.0, 95% CI:1.11-3.48) than diabetes-free participants. In the CIND cohort, 84 (13%) had diabetes and 238 (36%) prediabetes. During follow-up (mean 7.7 ± 4.0 years [range=0.2-15.2 years]), 132 (20%) individuals progressed to dementia. Poorly-controlled diabetes was associated with 3-times higher risk of dementia progression (HR 3.3, 95% CI: 1.29-8.33). Furthermore, comorbid heart disease and diabetes was associated with 2.5-times higher risk of progression to dementia (HR 2.5, 95% CI: 1.17-5.47), particularly if the diabetes was poorly-controlled (HR 5.8, 95% CI: 1.72-19.3). Similarly, having elevated CRP levels and diabetes was associated with increased risk of progression to dementia (HR 4.1, 95% CI: 1.15-14.2), especially in participants with poorly-controlled diabetes (HR 13.6, 95% CI: 1.89-98). No associations between prediabetes and CIND were detected in either cohort. Conclusions: Diabetes, especially if poorly-controlled, increases the risk of cognitive impairment and accelerates its progression to dementia. The diabetes-associated progression from CIND to dementia is further exacerbated by the presence of heart disease and elevated levels of systemic inflammation.
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(2019)Background: Despite the well-established link between diabetes and dementia risk, the impact of prediabetes and diabetes on the prodromal dementia phase remains controversial. In this study, we investigated whether prediabetes and diabetes increase the risk of cognitive impairment–no dementia (CIND) and accelerate its progression to dementia, as well as the possible underlying mechanisms. Methods: In the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), one cohort of cognitively-intact individuals (n=1,837) and one cohort of individuals with CIND (n=671) aged ≥60 years were followed for up to 15 years. At baseline and each follow-up (every 3 or 6 years), a neuropsychological test battery was administered, and the domains of episodic memory, processing speed, executive function, visuospatial abilities, and language were derived. CIND was defined as having no dementia and cognitive performance ≤1.5 SDs below age group-specific means in at least one cognitive domain. Dementia was diagnosed according to DSM-IV criteria. Diabetes (controlled and poorly-controlled) was diagnosed by physicians through medical assessment, clinical records, and glycated hemoglobin (HbA1c) ≥6.5%. Prediabetes was identified as HbA1c 5.7-6.4% in diabetes-free participants. Clinicians diagnosed heart disease and collected blood samples used to measure C-reactive protein (CRP). Data were analyzed with Cox regression models adjusted for possible confounders. Results: At baseline, in the cognitively-intact cohort, 133 (7%) participants had diabetes and 615 (34%) had prediabetes. During follow-up (mean 9.2 ± 3.0 years [range=2.2-15.5 years]), 544 (30%) individuals in the cognitively-intact cohort developed CIND. Poorly-controlled diabetes (HbA1c ≥7.5%) was associated with 2-times higher risk of CIND (HR 2.0, 95% CI:1.11-3.48) than diabetes-free participants. In the CIND cohort, 84 (13%) had diabetes and 238 (36%) prediabetes. During follow-up (mean 7.7 ± 4.0 years [range=0.2-15.2 years]), 132 (20%) individuals progressed to dementia. Poorly-controlled diabetes was associated with 3-times higher risk of dementia progression (HR 3.3, 95% CI: 1.29-8.33). Furthermore, comorbid heart disease and diabetes was associated with 2.5-times higher risk of progression to dementia (HR 2.5, 95% CI: 1.17-5.47), particularly if the diabetes was poorly-controlled (HR 5.8, 95% CI: 1.72-19.3). Similarly, having elevated CRP levels and diabetes was associated with increased risk of progression to dementia (HR 4.1, 95% CI: 1.15-14.2), especially in participants with poorly-controlled diabetes (HR 13.6, 95% CI: 1.89-98). No associations between prediabetes and CIND were detected in either cohort. Conclusions: Diabetes, especially if poorly-controlled, increases the risk of cognitive impairment and accelerates its progression to dementia. The diabetes-associated progression from CIND to dementia is further exacerbated by the presence of heart disease and elevated levels of systemic inflammation.
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(2023)Inflammatory bowel disease (IBD) is a chronic autoimmune disease, with recurring inflammation in the gastrointestinal tract. Although the actual cause of the disease is still unknown, many molecular and underlying pathways have been discovered. Infliximab (IFX) is an effective and safe antibody medication that specifically targets the cytokine protein TNF-α. This medication is given to IBD patients who do not respond to other conventional drugs and who face the final step of surgery. However, around 30 % of IBD patients do not respond to this medication at all and another 50 % either lose the effect over time, or need to discontinue the medication due to severe side effects. Therefore, it would be important to find a biomarker that could predict the outcome of the medication. In this study, 73 IBD patients have given blood samples both before and three months after the start of IFX medication. From these blood samples the RNA was extracted and sequenced to get the transcriptome profiles. The aim of this study is to find novel biomarkers, that could be used as a predictive tool for the outcome of the medication. Seven significantly differentially expressed genes were found before IFX treatment initiation between responders and non-responders of the medication. Additionally, a clear effect from the IFX medication was seen in the transcriptome profiles.
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(2023)Inflammatory bowel disease (IBD) is a chronic autoimmune disease, with recurring inflammation in the gastrointestinal tract. Although the actual cause of the disease is still unknown, many molecular and underlying pathways have been discovered. Infliximab (IFX) is an effective and safe antibody medication that specifically targets the cytokine protein TNF-α. This medication is given to IBD patients who do not respond to other conventional drugs and who face the final step of surgery. However, around 30 % of IBD patients do not respond to this medication at all and another 50 % either lose the effect over time, or need to discontinue the medication due to severe side effects. Therefore, it would be important to find a biomarker that could predict the outcome of the medication. In this study, 73 IBD patients have given blood samples both before and three months after the start of IFX medication. From these blood samples the RNA was extracted and sequenced to get the transcriptome profiles. The aim of this study is to find novel biomarkers, that could be used as a predictive tool for the outcome of the medication. Seven significantly differentially expressed genes were found before IFX treatment initiation between responders and non-responders of the medication. Additionally, a clear effect from the IFX medication was seen in the transcriptome profiles.
Now showing items 1-10 of 10