Lactobacillus casei strain Shirota selectively modulates macrophage subset cytokine production

Probiotics confer health benefits through many mechanisms including modulation of the gut immune system, dut macrophages regulate immune homeostasis, mounting tolerogenic responses to food and commensal bacteria or immune inflammatory responses to pathogens. Local environment and macrophage subset determine immune response and tolerance, associated with an M2-like phenotype and inflammatory activation with an Ml-like phenotype. Subset predominance will determine immunomodulatory effects of probiotic species such as Lactobacillus casei strain Shirota (LcS). The aim of this study was to investigate differential regulatory effects of LcS on Ml and M2 macrophage subsets. PMA or vitamin D3 differentiated THP-1 human monocytic cells were used to investigate heat-killed LcS and secreted protein tmmunoregulation of Ml and M2 cytokine production, respectively. Additionally, regulation of CD 14lo M2 and CD 14hiMl function was investigated Cytokine expression was measured by ELISA and NFkB activity by reporter assay. Both HK-LcS and SP-LcSaugmented IL-lβ, suppressed IL-6 and differentially regulated TNFα and IL-8, dependent on macrophage subset. HK-LcS and LcS-SP augmented CD14hi Ml TNFa whereas suppressed CD14lo M2 IL-6 and CD14hi Ml NFkB. In conclusion, LcS differentially regulates macrophage cytokines and NFkB activation, is subset-dependent and suggests a cautionary approach to probiotic treatment of mucosal inflammation. Copyright © 2012 by New Century Health Publishers, LLC

Social Media & its Effects On Decision Making of Senior Management

Organizations continue to realize the significant impact that information and communication technologies (ICTs) have on their day-to-day business processes. In educational institutions, access to learning resources, real-time communication, and access to research sources can be simplified by using these technologies (Kruger, 2010). Also, these institutions can enhance using the technology by integrating social methods into traditional approaches in several fields in the institutions. In practice, ICT-supported learning systems by improving interaction, better access to resources, reduced operating costs and reliable communication among students and public with the educational institutions’ management. One of these ICT techniques is the collaborative web which is rich in applications that can facilitate knowledge sharing, interaction, collaboration and communication (Munguatosha et al., 2011)

Lacticaseibacillus casei Strain Shirota Modulates Macrophage-Intestinal Epithelial Cell Co-Culture Barrier Integrity, Bacterial Sensing and Inflammatory Cytokines.

Probiotic bacteria modulate macrophage immune inflammatory responses, with functional cytokine responses determined by macrophage subset polarisation, stimulation and probiotic strain. Mucosal macrophages exhibit subset functional heterogeneity but are organised in a 3-dimensional tissue, over-laid by barrier epithelial cells. This study aimed to investigate the effects of the probiotic Lacticaseibacillus casei strain Shirota (LcS) on macrophage-epithelial cell cytokine responses, pattern recognition receptor (PRR) expression and LPS responses and the impacts on barrier integrity. THP-1-derived M1 and M2 subset macrophages were co-cultured in a transwell system with differentiated Caco-2 epithelial cells in the presence or absence of enteropathogenic LPS. Both Caco-2 cells in monoculture and macrophage co-culture were assayed for cytokines, PRR expression and barrier integrity (TEER and ZO-1) by RT-PCR, ELISA, IHC and electrical resistance. Caco-2 monocultures expressed distinct cytokine profiles (IL-6, IL-8, TNFα, endogenous IL-10), PRRs and barrier integrity, determined by inflammatory context (TNFα or IL-1β). In co-culture, LcS rescued ZO-1 and TEER in M2/Caco-2, but not M1/Caco-2. LcS suppressed TLR2, TLR4, MD2 expression in both co-cultures and differentially regulated NOD2, TLR9, Tollip and cytokine secretion. In conclusion, LcS selectively modulates epithelial barrier integrity, pathogen sensing and inflammatory cytokine profile; determined by macrophage subset and activation status

Heat-killed probiotic bacteria differentially regulate colonic epithelial cell production of human β-defensin-2: dependence on inflammatory cytokines.

The inducible antimicrobial peptide human β-defensin-2 (hBD-2) stimulated by pro-inflammatory cytokines and bacterial products is essential to antipathogen responses of gut epithelial cells. Commensal and probiotic bacteria can augment such mucosal defences. Probiotic use in the treatment of inflammatory bowel disease, however, may have adverse effects, boosting inflammatory responses. The aim of this investigation was to determine the effect of selected probiotic strains on hBD-2 production by epithelial cells induced by pathologically relevant pro-inflammatory cytokines and the role of cytokine modulators in controlling hBD-2. Caco-2 colonic intestinal epithelial cells were pre-incubated with heat-killed probiotics, i.e. Lactobacillus casei strain Shirota (LcS) or Lactobacillus fermentum strain MS15 (LF), followed by stimulation of hBD-2 by interleukin (IL)-1β and tumour necrosis factor alpha (TNF-α) in the absence or presence of exogenous IL-10 or anti-IL-10 neutralising antibody. Cytokines and hBD-2 mRNA and protein were analysed by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. LcS augmented IL-1β-induced hBD-2, whereas LF enhanced TNF-α- and suppressed IL-1β-induced hBD-2. LF enhanced TNF-α-induced TNF-α and suppressed IL-10, whereas augmented IL-1β-induced IL-10. LcS upregulated IL-1β-induced TNF-α mRNA and suppressed IL-10. Endogenous IL-10 differentially regulated hBD-2; neutralisation of IL-10 augmented TNF-α- and suppressed IL-1β-induced hBD-2. Exogenous IL-10, however, suppressed both TNF-α- and IL-1β-induced hBD-2; LcS partially rescued suppression in TNF-α- and IL-1β-stimulation, whereas LF further suppressed IL-1β-induced hBD-2. It can be concluded that probiotic strains differentially regulate hBD-2 mRNA expression and protein secretion, modulation being dictated by inflammatory stimulus and resulting cytokine environment

Probiotic bacterial strains differentially modulate macrophage cytokine production in a strain-dependent and cell subset-specific manner.

Gut mucosal macrophages play a pivotal role in driving mucosal immune responses, resulting in either activation of inflammatory immune responses to pathogenic challenge or tolerance to beneficial luminal contents such as food and commensal bacteria. Macrophage responses elicited are dependent on tissue environment and the resulting cell subset, where homeostatic macrophages resemble the M2 macrophage subset and inflammatory macrophages resemble M1s. Probiotics can modulate macrophage function with outcome dependent on subset present. Using a THP-1 monocyte cell line-derived model of CD14high/low M1 and M2 macrophages, the aim of this study was to investigate the immunomodulatory effects of a panel of heat-killed probiotic bacteria and their secreted proteins on the subset-specific inflammatory marker profile of TNFα, IL-6 and NFκB. M1 and M2 cells were generated by differentiation of monocyte stable transfectants for high and low CD14 expression with phorbol 12-myristate 13-acetate and vitamin D3, respectively, where the resulting CD14lo M2 and CD14hi M1s mimicked homeostatic and inflammatory mucosal macrophages. Subsets were stimulated by enteropathic lipopolysaccharides in the presence or absence of heat-killed (HK) or secreted proteins (SP) from a panel of probiotic bacteria. Regulation of cytokine expression was measured by ELISA and NFκB activity by reporter assay. HK probiotics suppress CD14lo and augment CD14hi M1 and M2 production of TNFα whereas SPs augmented CD14hi M1 TNFα and were generally suppressive in the other subtypes. M2 macrophage IL-6 production was suppressed by both HK and SPs and differentially regulated in CD14lo and CD14hi M1s. NFκB activation failed to parallel the regulatory profiles for TNFα and IL-6 which is suggestive of probiotic bacteria exerting their regulatory effects on these cytokines in an NFκB-independent manner. In conclusion, HK and SP probiotics differentially regulate macrophage cytokines and NFκB activation in a subset-dependent manner and suggest a cautionary approach to probiotic treatment of mucosal inflammation

Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy

Background: Progressive multifocal leukoencephalopathy (PML) was reported to have developed in three patients treated with natalizumab. We conducted an evaluation to determine whether PML had developed in any other treated patients. Methods: We invited patients who had participated in clinical trials in which they received recent or long-term treatment with natalizumab for multiple sclerosis, Crohn's disease, or rheumatoid arthritis to participate. The clinical history, physical examination, brain magnetic resonance imaging (MRI), and testing of cerebrospinal fluid for JC virus DNA were used by an expert panel to evaluate patients for PML. We estimated the risk of PML in patients who completed at least a clinical examination for PML or had an MRI. Results: Of 3417 patients who had recently received natalizumab while participating in clinical trials, 3116 (91 percent) who were exposed to a mean of 17.9 monthly doses underwent evaluation for PML. Of these, 44 patients were referred to the expert panel because of clinical findings of possible PML, abnormalities on MRI, or a high plasma viral load of JC virus. No patient had detectable JC virus DNA in the cerebrospinal fluid. PML was ruled out in 43 of the 44 patients, but it could not be ruled out in one patient who had multiple sclerosis and progression of neurologic disease because data on cerebrospinal fluid testing and follow-up MRI were not available. Only the three previously reported cases of PML were confirmed (1.0 per 1000 treated patients; 95 percent confidence interval, 0.2 to 2.8 per 1000). Conclusions: A detailed review of possible cases of PML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalizumab for a mean of 17.9 months. The risk associated with longer treatment is not known

Sexual Behaviour among Male Methamphetamine and Heroin Dependents in Selected Areas in Malaysia (Tingkah-laku Seksual dalam Kalangan Lelaki Ketagihan Metamfetamin dan Heroin di Beberapa Tempat di Malaysia)

ABSTRACT This study aims to describe the pattern of sexual behaviour among methamphetamine and heroin users. I

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22824 adults

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele