Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation.

Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4) in microglia's inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3) released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection) and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain

Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation

<p>Abstract</p> <p>Background</p> <p>To identify the genetic defect associated with autosomal recessive congenital cataract (ARCC), mental retardation (MR) and ARCC, MR and microcephaly present in most patients in four Tunisian consanguineous families.</p> <p>Methods</p> <p>We screened four genes implicated in congenital cataract by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly. Among its three genes <it>PAX6</it>, <it>PITX3 </it>and <it>HSF4 </it>are expressed in human brain and one gene <it>LIM2 </it>encodes for the protein MP20 that interact with the protein galectin-3 expressed in human brain and plays a crucial role in its development. All genes were screened by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly.</p> <p>Results</p> <p>We report no mutation in the four genes of congenital cataract and its flanking regions. Only variations that did not segregate with the studied phenotypes (ARCC associated to MR, ARCC associated with MR and microcephaly) are reported. We detected three intronic variations in <it>PAX6 </it>gene: IVS4 -274insG (intron 4), IVS12 -174G>A (intron12) in the four studied families and IVS4 -195G>A (intron 4) in two families. Two substitutions polymorphisms in <it>PITX3 </it>gene: c.439 C>T (exon 3) and c.930 C>A (exon4) in one family. One intronic variation in <it>HSF4 </it>gene: IVS7 +93C>T (intron 7) identified in one family. And three intronic substitutions in <it>LIM2 </it>gene identified in all four studied families: IVS2 -24A>G (intron 2), IVS4 +32C>T (intron 4) and c.*15A>C (3'-downstream sequence).</p> <p>Conclusion</p> <p>Although the role of the four studied genes: <it>PAX6</it>, <it>PITX3</it>, <it>HSF4 </it>and <it>LIM2 </it>in both ocular and central nervous system development, we report the absence of mutations in all studied genes in four families with phenotypes associating cataract, MR and microcephaly.</p

Inflammation in experimental neonatal brain injury and in a clinical study of preterm birth; involvement of galectin-3 and free radical formation

Introduction; Intrauterine infection/inflammation is associated with preterm delivery (PTD) and severe neonatal morbidity. Inflammation is also important in the secondary neurotoxic cascade leading to perinatal brain injury. The aims were to investigate (a) the novel inflammatory marker galectin-3 that affects accumulation, apoptosis and activation of inflammatory cells and (b) free radical formation in particular by the enzyme NADPH-oxidase responsible for free radical formation in inflammatory cells, in threatening PTD (III) and in the development of experimental perinatal brain injury (I,II). Materials and methods; Amniotic fluid (AF) and placentas were obtained from 83 women with threatening PTD presenting with preterm labour (PTL) or premature prelabour rupture of membranes (pPROM) and from 15 term controls. AF was analysed for galectin-3, ascorbyl radicals and antioxidative capacity (AOC) and results were correlated to signs of intrauterine infection/inflammation, PTD and severe neonatal morbidity (III). In the experimental studies, models of term hypoxia-ischemia (HI) (I,II) and of excitotoxic white matter injury (I) were used in knock-out (KO) mice for galectin-3 (II) and gp91phox (a subunit in NADPH-oxidase) (I) and together with two inhibitors of NADPH oxidase (I). Lesion size, inflammation (microglia accumulation, inflammatory mediators), free radical formation, apoptosis and trophic factors were studied. In vitro studies were used to investigate free radical formation in microglial cells (I) and the effect of AF on pre-activated neutrophils (III). Results; Galectin-3, ascorbyl radicals and AOC were detected in all AF samples. Women with threatening PTD and infection/inflammation had higher levels of galectin-3 and slow AOC but lower levels of ascorbyl radicals than term controls but without correlation to PTD. Mothers of girls had higher levels galectin-3 than mothers of boys. AF also quenched free radical formation in primed neutrophils in vitro. Women with PTL did not differ from women with pPROM. Only AOC was increased in mothers to infants with severe morbidity (III). After experimental HI, mRNA expression of galectin-3 and NADPH-oxidase subunits (I,II) as well as galectin-3 protein expression were increased (II). Galectin-3 KO mice had reduced injury but increased microglial density and reduced expression of inflammatory factors (MMP-9) and markers for oxidative stress (nitrotyrosine). The protection was more pronounced in males. Apoptosis was altered in un-operated KO mice but not after HI. No difference was seen for trophic factors (II). Pharmacological inhibition of NADPH-oxidase reduced free radical formation in vitro and markers of oxidative stress in vivo, but resulted in an increase in apoptotic markers and lesion size after excitotoxic injury. Genetic inhibition did not reduce injury but resulted in an increase of the inflammatory markers galectin-3 and IL-1β (I). Conclusion; Galectin-3 is increased in women with threatening PTD and associated infection/inflammation,but our findings suggest a strong antioxidative capacity and not an increased oxidative stress as previously suggested (III). Galectin-3 contributes to neonatal brain injury by modulating the inflammatory response rather than affecting apoptosis or trophic factors and the mechanisms may be sex dependent (II). Contrary to findings in the adult brain, perinatal brain injury was unaltered or aggravated after genetic and pharmacological NADPH-oxidase inhibition (I)

The inclusion of Shool-age educare centres in the work to promote mental health and prevent mental illness

School-age educare centers have an important environment where children spend a significant part of their time. The school-age educare center’s preventive work is based on different methods and strategies.An integrated and inclusive pedagogy promotes positive relationships between children and increases their sense of belonging. Trained educators and staff play a key role in creating safe and supportive environments where children can develop their social skills.The purpose of the study is to take a closer look at how schools and their student health services include after-school centers in health promotion work. The method that we have chosen to collect data is based on a qualitative method, consisting of questionnaires with open-ended questions in which principals, student health services and school-age educare centers answered questions about inclusion, prevention,and skills development. We have based our work on previous research on prevention and health promotion in the school as a whole and the contribution of after-school centers to health promotion. The theory chosen for the study is KASAM and the intercultural perspective and its concepts are mental illness and mental health. Results and analyses show that principals and student health services have a holistic approach to health promotion and prevention work aimed at schools, but after-school centers educators are not included in this work on the same terms as schoolteachers. The research in our final discussion shows that everyone / all involved including the after-school centers needs to work together in the prevention of mental health problems.Fritidshemmet utgör en viktig miljö där barn tillbringar en betydande del av sin tid.Fritidshemmets förebyggande arbete bygger på olika metoder och strategier.En integrerad och inkluderande pedagogik främjar positiva relationer mellan barn och ökar deras känsla av samhörighet. Utbildade pedagoger och personal spelar en nyckelroll genom att skapa trygga och stödjande miljöer där barn kan utveckla sina sociala färdigheter.Syftet med studien är att tittat närmare på hur skolan och skolornas elevhälsa inkluderar fritidshemmen i ett hälsofrämjande arbete. Metoden som vi har valt för att samla in data bygger på en kvalitativ metod, bestående av enkäter med öppna frågor som i ett led där rektorer, elevhälsan och fritidshemmen besvarat frågor som berör inkludering, förebyggande arbete samt kompetensutveckling. Vi har utgått från tidigare forskning inom förebyggande och hälsofrämjande insatser i skolan som helhet och vad tillförande avfritidshemmen ger i de hälsofrämjande arbetet. Teorin som har valts för studien är utifrån KASAM och det interkulturella perspektivet och dess begrepp är lärmiljö, psykisk ohälsa och psykisk hälsa. Resultat och analys visar att rektorer och elevhälsan har en helhetssyn men deras insatser riktas mot skolan och lärare, fritidshemmen inkluderas inte på lika villkor som pedagoger i skolan. Forskningen i vår slutdiskussion visar att alla behöver arbeta tillsammans i förebyggandet mot psykisk ohälsa

Produktutveckling av textila reparationsmaterial

Den här rapporten behandlar ämnet textila reparationsmaterial. Det är en uppsats på kandidatnivå som har en praktisk ansats och syftar till att produktutveckla för att lösa ett vardagsproblem med arbetskläder som slits ojämnt och därför ofta kasseras i förtid. Nyttan av rapporten är både en tidsbesparing för alla som använder arbetsbyxor som ofta slits sönder i förtid samt den sett ur ett mlijöperspektiv då livslängden för arbetsbyxan utökas när den lagas. För att uppnå detta är det av största vikt att produkten samt applikationen är okomplicerad. Ett antal olika dubbelhäftande tape (adhesive) och smältfilmslim (termoplastiska polyuretaner TPU) har satts samman med tre olika typer av textila varukonstruktioner och textila material, varptrikå i polyester, polyestertwill och bomullstwill. De textila varukonstruktioner som tagits fram för att sättas samman med adhesivet och limfilmen har valts för att testa huruvida den textila strukturen påverkar vidhäftningen. Det material som har valts ut, för att applicera de olika prototyperna av reparationsmaterialet på, är samma bomullstwill som återfinns bland de textila varukonstruktionerna. Av vår marknadsundersökning kan man utläsa att bomullstwill är ett av de vanligast förekommande materialen och textila varukonstruktionerna i ledande producenters arbetsbyxor. Tester har utförts i fem steg och två testomgångar baserat på “Textiles Domestic washing and drying procedures for textile testing”, ISO standard 6330:2012 och med tydliga beskrivningar och illustrationer för att säkerställa kredibiliteten av resultatet. Ett manuellt dragtest har utförts för att efterlikna de påfrestningar produkten behöver utstå under använding. Resultaten av rapporten visar att det går att konstruera ett textilt reparationsmaterial med mycket god vidhäftning och en okomplicerad applikation

Produktutveckling av textila reparationsmaterial

Den här rapporten behandlar ämnet textila reparationsmaterial. Det är en uppsats på kandidatnivå som har en praktisk ansats och syftar till att produktutveckla för att lösa ett vardagsproblem med arbetskläder som slits ojämnt och därför ofta kasseras i förtid. Nyttan av rapporten är både en tidsbesparing för alla som använder arbetsbyxor som ofta slits sönder i förtid samt den sett ur ett mlijöperspektiv då livslängden för arbetsbyxan utökas när den lagas. För att uppnå detta är det av största vikt att produkten samt applikationen är okomplicerad. Ett antal olika dubbelhäftande tape (adhesive) och smältfilmslim (termoplastiska polyuretaner TPU) har satts samman med tre olika typer av textila varukonstruktioner och textila material, varptrikå i polyester, polyestertwill och bomullstwill. De textila varukonstruktioner som tagits fram för att sättas samman med adhesivet och limfilmen har valts för att testa huruvida den textila strukturen påverkar vidhäftningen. Det material som har valts ut, för att applicera de olika prototyperna av reparationsmaterialet på, är samma bomullstwill som återfinns bland de textila varukonstruktionerna. Av vår marknadsundersökning kan man utläsa att bomullstwill är ett av de vanligast förekommande materialen och textila varukonstruktionerna i ledande producenters arbetsbyxor. Tester har utförts i fem steg och två testomgångar baserat på “Textiles Domestic washing and drying procedures for textile testing”, ISO standard 6330:2012 och med tydliga beskrivningar och illustrationer för att säkerställa kredibiliteten av resultatet. Ett manuellt dragtest har utförts för att efterlikna de påfrestningar produkten behöver utstå under använding. Resultaten av rapporten visar att det går att konstruera ett textilt reparationsmaterial med mycket god vidhäftning och en okomplicerad applikation

Galectin-3 contributes to neonatal hypoxic-ischemic brain injury.

International audienceInflammation induced by hypoxia-ischemia (HI) contributes to the development of injury in the newborn brain. In this study, we investigated the role of galectin-3, a novel inflammatory mediator, in the inflammatory response and development of brain injury in a mouse model for neonatal HI. Galectin-3 gene and protein expression was increased after injury and galectin-3 was located in activated microglia/macrophages. Galectin-3-deficient mice (gal3-/-) were protected from injury particularly in hippocampus and striatum. Microglia accumulation was increased in the gal3-/- mice but accompanied by decreased levels of total matrix metalloproteinase (MMP)-9 and nitrotyrosine. The protection and increase in microglial infiltration was more pronounced in male gal3-/- mice. Trophic factors and apoptotic markers did not significantly differ between groups. In conclusion, galectin-3 contributes to neonatal HI injury particularly in male mice. Our results indicate that galectin-3 exerts its effect by modulating the inflammatory response

Expression of cytokines and chemokines in cervical and amniotic fluid: Relationship to histological chorioamnionitis

Objective. To correlate cervical and amniotic fluid cytokines and macrophage-related chemokines to the development of histological chorioamnionitis (HCA) in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PPROM). Study design. Cervical and amniotic fluid interleukin (IL)-6, IL-8, IL-18, monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 from pregnant women (at </=34 weeks of gestation) in PTL (N = 42) were analyzed and related to the subsequent occurrence of HCA or inflammatory signs in the placenta. For the patients with PPROM (N = 30) only amniotic fluid proteins were analyzed. Results. Intra-amniotic levels of IL-6, IL-8, IL-18, MCP-1, and MCP-3 were significantly higher in PTL cases with HCA compared to non-HCA controls, whereas no such relationship was obtained in the PPROM group. Cervical IL-8 and IL-6 (but not IL-18, MCP-1, MCP-2, and MCP-3) in PTL patients was associated with HCA, and at a cut-off level of 10.0 ng/mL cervical IL-8 was a strong predictor of HCA in the PTL cases (sensitivity 100%, specificity 67%, positive predictive value 63%, negative predictive value 100%). The cytokine and chemokine levels in the group with inflammatory signs were generally higher than in controls but lower compared to the concentrations in the HCA group. Conclusions. The amniotic levels of IL-6, IL-8, IL-18, and the CC-chemokines MCP-1 and MCP-3 in PTL patients all predicted HCA, whereas only IL-8 was a clinically useful marker of HCA in the cervical fluid. In addition there is indication that the levels of inflammatory proteins are related to the degree of inflammatory infiltration in placental tissue samples

Genetic variation in galectin-3 gene associates with cognitive function at old age

Inflammation plays an important role in the development of cognitive decline and dementia in old age. Galectin-3 is known for its role in acute and chronic inflammation. We assessed whether genetic variation in the LGALS3 gene, encoding for galectin-3, associates with cognitive function in the 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). The rs4644, rs4652, and rs1009977 polymorphisms were genotyped to cover the genomic region of the LGALS3 gene. Subjects carrying the variant alleles of each LGALS3 single nucleotide polymorphism (SNP) had significantly higher baseline C-reactive protein concentrations (p &lt; 0.01). Carriers of the variant alleles had significantly worse performance at baseline compared with carriers of the wild-type allele (all p &lt; 0.05). In the longitudinal analysis, we found that carriers of the variant alleles had worse performance at the attention tasks compared with carriers of the wild-type allele. Although observed differences were small, these data suggest that genetic variation in the LGALS3 gene might be associated with cognitive function in an elderly population. Further research is warranted to confirm these results