| 1. |
- Allahgholi, Leila, et al.
(författare)
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Fermentation of the Brown Seaweed Alaria esculenta by a Lactic Acid Bacteria Consortium Able to Utilize Mannitol and Laminari-Oligosaccharides
- 2023
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Ingår i: Fermentation. - 2311-5637. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- The brown seaweed Alaria esculenta is the second most cultivated species in Europe, and it is therefore of interest to expand its application by developing food products. In this study, a lactic acid bacteria consortium (LAB consortium) consisting of three Lactiplantibacillus plantarum strains (relative abundance ~94%) and a minor amount of a Levilactobacillus brevis strain (relative abundance ~6%) was investigated for its ability to ferment carbohydrates available in brown seaweed. The consortium demonstrated the ability to ferment glucose, mannitol, galactose, mannose, and xylose, of which glucose and mannitol were the most favored substrates. No growth was observed on fucose, mannuronic and guluronic acid. The consortium used different pathways for carbohydrate utilization and produced lactic acid as the main metabolite. In glucose fermentation, only lactic acid was produced, but using mannitol as a carbohydrate source resulted in the co-production of lactic acid, ethanol, and succinate. Xylose fermentation resulted in acetate production. The consortium was also able to utilize laminari-oligosaccharides (DP2-4), obtained after enzymatic hydrolysis of laminarin, and produced lactic acid as a metabolite. The consortium could grow directly on A. esculenta, resulting in a pH decrease to 3.8 after 7 days of fermentation. Incubation of the same seaweed in corresponding conditions without inoculation resulted in spoilage of the seaweed by endogenous bacteria.
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| 2. |
- Asaduzzaman, Muhammad, et al.
(författare)
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LFA-1 AND MAC-1 MEDIATE PULMONARY RECRUITMENT OF NEUTROPHILS AND TISSUE DAMAGE IN ABDOMINAL SEPSIS.
- 2008
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1540-0514 .- 1073-2322. ; 30, s. 254-259
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil-mediated lung damage is an insidious feature in septic patients, although the adhesive mechanisms behind pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. The aim of the present study was to define the role of lymphocyte function-antigen 1 (LFA-1) and membrane-activated complex 1 (Mac-1) in septic lung injury. Pulmonary edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, and CXC chemokines were determined after cecal ligation and puncture (CLP). Mice were treated with monoclonal antibodies directed against LFA-1 and Mac-1 before CLP induction. Cecal ligation and puncture induced clear-cut pulmonary damage characterized by edema formation, neutrophil infiltration, and increased levels of CXC chemokines in the lung. Notably, immunoneutralization of LFA-1 or Mac-1 decreased CLP-induced neutrophil recruitment in the bronchoalveolar space by more than 64%. Moreover, functional inhibition of LFA-1 and Mac-1 abolished CLP-induced lung damage and edema. However, formation of CXC chemokines in the lung was intact in mice pretreated with the anti-LFA-1 and anti-Mac-1 antibodies. Our data demonstrate that both LFA-1 and Mac-1 regulate pulmonary infiltration of neutrophils and lung edema associated with abdominal sepsis. Thus, these novel findings suggest that LFA-1 or Mac-1 may serve as targets to protect against lung injury in polymicrobial sepsis.
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| 3. |
- Bredberg, Anders, et al.
(författare)
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Targeting versus tinkering: Explaining why the clinic is frustrated with molecular mapping of disease mechanisms.
- 2013
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Ingår i: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 81:4, s. 553-556
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Tidskriftsartikel (refereegranskat)abstract
- We argue that our common diseases should not necessarily be taken as a sign of physiological error. Regulatory networks developed by evolutionary forces to support reproductive fitness happen to include disease as a side-effect. For example, inflammatory and autoimmune diseases are secondary to a strong defence against infections. An evolutionary perspective can help us understand why many drugs targeted to single molecules or linear signaling pathways fail in clinical trials. We present the hypothesis that a tinkering research strategy, as compared with the prevailing reductionist approach, may be more likely to help us find the tools needed to interfere optimally with disease-generating networks. One application of the hypothesis can be to analyze how manipulation with diet and gut microbial flora influences multiple sclerosis patients, rather than to first map in detail the molecular disease mechanism and then develop targeting drugs.
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| 4. |
- Dold, Stefan, et al.
(författare)
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Cholestatic liver damage is mediated by lymphocyte function antigen-1-dependent recruitment of leukocytes.
- 2008
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Ingår i: Surgery. - : Elsevier BV. - 1532-7361 .- 0039-6060. ; 144:3, s. 385-393
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of specific adhesion molecules in cholestasis-induced leukocyte recruitment in the liver is not known. Therefore, the aim of our experimental study was to evaluate the role of lymphocyte function antigen-1 (LFA-1) in cholestatic liver injury. METHODS: C57BL/6 mice underwent bile duct ligation for 12 hours. Mice were pretreated with an anti-LFA-1 antibody or control antibody. Subsequently, hepatic accumulation of leukocytes and sinusoidal perfusion were determined by means of intravital fluorescence microscopy. Hepatocellular damage was monitored by measuring serum levels of alanine aminotransferase and aspartate aminotransferase. CXC chemokines in the liver were determined by enzyme-linked immunosorbent assay. RESULTS: Bile duct ligation provoked clear-cut recruitment of leukocytes and liver damage, as indicated by increased serum activities of liver enzymes and sinusoidal perfusion failure. Neutrophils expressed greater levels of LFA-1 and inhibition of LFA-1 significantly decreased serum activity of alanine aminotransferase and aspartate aminotransferase levels in cholestatic mice. Immunoneutralization of LFA-1 reduced leukocyte adhesion in postsinusoidal venules that had been induced by bile duct ligation, whereas leukocyte rolling and sinusoidal accumulation were not changed. Moreover, blocking LFA-1 function restored sinusoidal perfusion in cholestatic animals. CONCLUSION: These findings demonstrate an important role of LFA-1 in supporting cholestasis-induced leukocyte recruitment in the liver. Thus, targeting LFA-1 may help to protect against pathologic inflammation and liver damage in cholestatic liver diseases.
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| 5. |
- Dold, Stefan, et al.
(författare)
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Simvastatin protects against cholestasis-induced liver injury.
- 2009
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 156, s. 466-474
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bile duct obstruction is associated with hepatic accumulation of leukocytes and liver injury. The aim of this study was to evaluate the effect of simvastatin on cholestasis-induced liver inflammation and tissue damage. Experimental approach: C57BL/6 mice were treated with simvastatin (0.02 and 0.2 mg.kg(-1)) and vehicle before and after undergoing bile duct ligation (BDL) for 12 h. Leukocyte recruitment and microvascular perfusion in the liver were analysed using intravital fluorescence microscopy. CXC chemokines in the liver were determined by enzyme-linked immunosorbent assay. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatic levels of myeloperoxidase (MPO) were also determined. Key results: Administration of 0.2 mg.kg(-1) simvastatin decreased ALT and AST by 87% and 83%, respectively, in BDL mice. This dose of simvastatin reduced hepatic formation of CXC chemokines by 37-82% and restored sinusoidal perfusion in cholestatic animals. Moreover, BDL-induced leukocyte adhesion in sinusoids and postsinusoidal venules, as well as MPO levels in the liver, was significantly reduced by simvastatin. Notably, administration of 0.2 mg.kg(-1) simvastatin 2 h after BDL induction also decreased cholestatic liver injury and inflammation. Conclusions and implications: These findings show that simvastatin protects against BDL-induced liver injury. The hepatoprotective effect of simvastatin is mediated, at least in part, by reduced formation of CXC chemokines and leukocyte recruitment. Thus, our novel data suggest that the use of statins may be an effective strategy to protect against the hepatic injury associated with obstructive jaundice.
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| 6. |
- Emami Aleagha, Mohammad Sajad, et al.
(författare)
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Differential Expression of Klotho in the Brain and Spinal Cord is Associated with Total Antioxidant Capacity in Mice with Experimental Autoimmune Encephalomyelitis
- 2018
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Ingår i: Journal of Molecular Neuroscience. - : Springer Science and Business Media LLC. - 0895-8696 .- 1559-1166. ; 64:4, s. 543-550
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we reported a positive correlation between Klotho, as an anti-aging protein, and the total antioxidant capacity (TAC) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, there is no information about the Klotho and TAC changes within the central nervous system (CNS). Thus, the current study aimed to employ an experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice using MOG35–55 peptide to examine the relationship between Klotho and TAC within the CNS. To this end, the brain and spinal cord were obtained at the onset and peak stages of EAE as well as non-EAE mice (sham/control groups). The Klotho expression was assessed in the brain and spinal cord of different experimental groups at mRNA (qPCR) and protein (ELISA) levels. Also, TAC level was determined in the tissues of different experimental groups. The results showed that Klotho expression in the brain at the onset and peak stages of EAE were significantly lower than that in non-EAE mice. Conversely, Klotho expression in the spinal cord at the onset of EAE was significantly higher than that of non-EAE mice, while Klotho was comparable at the peak stage of EAE and non-EAE mice. The pattern of TAC alteration in the brain and spinal cord of EAE mice was similar to that of Klotho expression. In conclusion, for the first time, this study demonstrated a significant positive correlation between Klotho and TAC changes during the pathogenesis of EAE. It is suggested that Klotho may have neuroprotective activity through the regulation of redox system.
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| 7. |
- Lavasani, Shahram, et al.
(författare)
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A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells.
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). One potential therapeutic strategy for MS is to induce regulatory cells that mediate immunological tolerance. Probiotics, including lactobacilli, are known to induce immunomodulatory activity with promising effects in inflammatory diseases. We tested the potential of various strains of lactobacilli for suppression of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. METHODOLOGY/PRINCIPAL FINDINGS: The preventive effects of five daily-administered strains of lactobacilli were investigated in mice developing EAE. After a primary screening, three Lactobacillus strains, L. paracasei DSM 13434, L. plantarum DSM 15312 and DSM 15313 that reduced inflammation in CNS and autoreactive T cell responses were chosen. L. paracasei and L. plantarum DSM 15312 induced CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) and enhanced production of serum TGF-beta1, while L. plantarum DSM 15313 increased serum IL-27 levels. Further screening of the chosen strains showed that each monostrain probiotic failed to be therapeutic in diseased mice, while a mixture of the three lactobacilli strains suppressed the progression and reversed the clinical and histological signs of EAE. The suppressive activity correlated with attenuation of pro-inflammatory Th1 and Th17 cytokines followed by IL-10 induction in MLNs, spleen and blood. Additional adoptive transfer studies demonstrated that IL-10 producing CD4(+)CD25(+) Tregs are involved in the suppressive effect induced by the lactobacilli mixture. CONCLUSIONS/SIGNIFICANCE: Our data provide evidence showing that the therapeutic effect of the chosen mixture of probiotic lactobacilli was associated with induction of transferable tolerogenic Tregs in MLNs, but also in the periphery and the CNS, mediated through an IL-10-dependent mechanism. Our findings indicate a therapeutic potential of oral administration of a combination of probiotics and provide a more complete understanding of the host-commensal interactions that contribute to beneficial effects in autoimmune diseases.
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| 8. |
- Lavasani, Shahram, et al.
(författare)
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Abnormal DNA damage-inducible protein in cells from Sjogren's syndrome patients
- 1998
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 11:4, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- Antinuclear antibodies are commonly found in patients with Sjogren's syndrome. It has been suggested that the development of antinuclear antibodies depends on the activation of the spliceosome and other transcription-related subcellular particles, some of which have recently been shown also to function in DNA-modifying processes, such as DNA repair and V(D)J recombination. These observations add weight to a previously proposed model for the aetiology of Sjogren's syndrome. This includes the abnormal processing of the T-cell receptor and immunoglobulin genes. To test this hypothesis further, the present study on DNA-modifying proteins in Sjogren's syndrome was initiated. Gel-shift experiments using protein extracted from UV-treated Sjogren cells provided evidence of high molecular weight DNA-binding protein in six out of 12 Sjogren patients studied (but not among seven healthy controls). Some Sjogren sera displayed antibodies to protein extracts from cells treated with psoralen plus UVA radiation. These results indicate an abnormal DNA damage-inducible response in Sjogren's syndrome. It may therefore be concluded that alterations in nuclear protein may play a role in the aetiology of Sjogren's syndrome.
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| 9. |
- Lavasani, Shahram, et al.
(författare)
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Monoclonal Antibody against T-Cell Receptor alphabeta Induces Self-Tolerance in Chronic Experimental Autoimmune Encephalomyelitis.
- 2007
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 65:1, s. 39-47
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Tidskriftsartikel (refereegranskat)abstract
- The therapeutic effect of monoclonal antibody (H57-597 MoAb) against T-cell receptor (TCR) alpha beta has been investigated on MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE), as a model system for T-cell-mediated chronic inflammation in the central nervous system (CNS). Short-term administration of the anti-TCR alpha beta immediately after immunization protected the mice from EAE. Furthermore, anti-TCR alpha beta treatment on an established disease restored the self-tolerance which led to a complete remission of EAE and a dramatic reduction of inflammatory cells in the CNS, while treatment with control antibody (hamster IgG) was ineffective. The remission was durable and not associated with disappearance of autoreactive T cells as measured by persistence of MOG-reactive T-cell proliferation in vitro. However, MOG-reactive T cells from anti-TCR-treated animals produced significantly lower amounts of inflammatory TNF-alpha and IFN-gamma. In addition, while a transient deletion of CD4(+) and CD8(+) T cells was observed, a population of T cells expressing CD3, NK1.1 and CD69 (NKT cells) were expanding. By transfer of spleen cells from anti-TCR MoAb-treated animals, we could show that the tolerogenic capacity can be transferred to untreated recipients with EAE. The data indicate therapeutic effect of anti-TCR alpha beta MoAb (H57-597), which represents a promising approach in treatment of T-cell-mediated autoimmune diseases.
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| 10. |
- Lavasani, Shahram
(författare)
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Novel Immunotherapies and Immunoregulation in a Chronic Inflammatory Disease of the Central Nervous System
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS) which is thought to arise from a breakdown of immunological tolerance in CD4 cells. The aim of this thesis is to improve our understanding of regulation mechanisms of T cell-dependent chronic inflammation in the CNS and explore ways to overcome the onset and progression of the disease, which can be an important step forward in the treatment of MS. We have utilized the Experimental Autoimmune Encephalomyelitis (EAE), as a mouse model for MS. Chronic EAE was induced by immunization with the myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide. MOG-reactive inflammatory CD4+ T cells infiltrate the CNS and, in concert with other mononuclear cells, cause inflammation and progressive paralysis. The focus of the first study was to evaluate the immunoregulatory role of CD1d-restricted T cells by using CD1d deficient mice. Our results suggest a regulatory role of CD1d-restricted T cells in EAE. This regulation functions through limiting the autoreactive T cell cytokine responses and enhancing TGF-beta1 production in the CNS. In another study, we investigated the therapeutic potential of monoclonal antibody (H57-597 mAb) against the T cell receptor (TCR) alpha/beta. We demonstrated that short term administration of anti-TCR alpha/beta can protect mice from EAE and is tolerogenic in established chronic EAE. We concluded that treatment with anti-TCR alpha/beta restores self-tolerance through a transient deletion of T cells including the autoreactive populations and a selective expansion of regulatory NKT cells. Finally, we evaluated the immunosuppressive potential of various probiotic bacteria strains in chronic EAE. We showed that oral administration of Lactobacillus paracasei DSM 13434, Lactobacillus plantarum DSM 15312 or Lactobacillus plantarum DSM 15313 suppressed EAE development by down-regulating autoreactive Th1 cells. The protective effect of the probiotic treatment was shown to be associated with an expansion of regulatory T cells in mesenteric lymph nodes and spleen followed by an increased production of IL-4, IL-10 and TGF-beta. We further demonstrated the powerful therapeutic potential of these bacteria in diseased animals when treating with a combination of these probiotic strains.
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