Anti-inflammatory and immune-modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation

Autoreactive inflammatory CD4+ T cells, such as T helper (Th)1 and Th17 subtypes, have been found to associate with the pathogenesis of autoimmune disorders. On the other hand, CD4+ Foxp3+ T regulatory (Treg) cells are crucial for the immune tolerance and have a critical role in the suppression of the excessive immune and inflammatory response promoted by these Th cells. In contrast, dendritic cells (DCs) and macrophages are immune cells that through their inflammatory functions promote autoreactive T-cell responses in autoimmune conditions. In recent years, there has been increasing attention to exploring effective immunomodulatory or anti-inflammatory agents from the herbal collection of traditional medicine. Berberine, an isoquinoline alkaloid, is one of the main active ingredients extracted from medicinal herbs and has been shown to exert various biological and pharmacological effects that are suggested to be mainly attributed to its anti-inflammatory and immunomodulatory properties. Several lines of experimental study have recently investigated the therapeutic potential of berberine for treating autoimmune conditions in animal models of human autoimmune diseases. Here, we aimed to seek mechanisms underlying immunomodulatory and anti-inflammatory effects of berberine on autoreactive inflammatory responses in autoimmune conditions. Reported data reveal that berberine can directly suppress functions and differentiation of pro-inflammatory Th1 and Th17 cells, and indirectly decrease Th cell-mediated inflammation through modulating or suppressing other cells assisting autoreactive inflammation, such as Tregs, DCs and macrophages. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Lt

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

Background: Hypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP). Methods and Findings: Three population-based EUROCAT congenital anomaly registries- Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010)—were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06–2.11), and the composite adverse outcome of 'anomaly or stillbirth' (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03–1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99–1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12–1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression. Conclusion: The additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care

Uso da plataforma social mídia na prática docente universitária: pesquisa biográfico-narrativa em um estudo de caso.

Este artículo busca comprender por qué y cómo se incorporan los medios sociales en la docencia de un profesor universitario. Los medios sociales son considerados como plataformas interactivas de comunicación relacionadas con la web 2.0 (web social), las cuales permiten generar contenidos, construir y compartir información y conocimiento entre diversos usuarios, favoreciendo el aprendizaje colaborativo social o el denominado aprendizaje 2.0, enmarcado en la visión de ciudadanos reflexivos, comprometidos con su devenir individual y colectivo. El enfoque cualitativo de este trabajo permitió la utilización de técnicas biográfico-narrativas de la investigación social, centrándose en el método de estudio de caso único. Se aplicaron cuatro entrevistas en profundidad al estudio de caso, que posteriormente fueron transcritas, y se realizó un relato que evidenció procesos comunicativos, didáctica, trayectorias, transiciones y transformaciones de su práctica docente.This article seeks to understand why and how social media is incorporated in the teaching of a university professor. Social media is considered as an interactive communication platform related to web 2.0 (social web), which can generate contents, build, share information and knowledge among different users, favoring social collaborative learning or the so-called learning 2.0, that is framed in the vision of thoughtful citizens committed to their individual and collective evolution. The qualitative approach of this work allowed the use of biographical-narrative techniques of social research, by focusing on the single case study method. Four interviews were applied in-depth to the case study, which were subsequently transcribed, and a narrative process was carried out that showed communication processes, didactic, trajectories, transitions and transformations of their teaching practice.Este artigo procura compreender por que e como é que se incorporam as mídias sociais na docência de um professor universitário. As mídias sociais são consideradas como plataformas interativas de comunicação relacionadas com a página web 2.0 (web social), as quais permitem gerar conteúdos, construir e compartilhar informação e conhecimento entre diversos utentes, favorecendo a aprendizagem colaborativa social ou a nomeada aprendizagem 2.0, enquadrada na visão de cidadãos reflexivos, comprometidos com seu devir individual e coletivo. A abordagem qualitativa deste trabalho permitiu a utilização de técnicas biográficonarrativas da pesquisa social, se centrando no método de estudo de caso único. Quatro entrevistas em profundidade foram aplicadas ao estudo de caso e posteriormente transcritas, e realizou-se um relato que evidenciou processos comunicativos, didática, trajetórias, transições e transformações de sua prática docente

Curcumin as a potential modulator of M1 and M2 macrophages: new insights in atherosclerosis therapy

Accumulation of macrophages within the artery wall is an eminent feature of atherosclerotic plaques. Macrophages are influenced by various plaque microenvironmental stimuli, such as oxidized lipids, cytokines, and senescent erythrocytes, and thereby polarize into two main phenotypes called proinflammatory M1 and anti-inflammatory M2 macrophages. In the hemorrhagic zones of atheroma, upon exposure to iron, sequestration of iron by M1 macrophages results in an uncontrolled proinflammatory phenotype impairing wound healing, while M2 macrophages phagocytose both apoptotic cells and senescent erythrocytes. M1 macrophages are prominent phenotype in the unstable plaques, in which plaque shoulder contains macrophages mainly present markers of M1 phenotype, whereas the fibrous cap encompassing the necrotic lipid core content macrophages expressed markers of both M1 and M2 subtypes. The abovementioned findings suggest macrophage modulation as a potent approach for atherosclerosis therapy. Curcumin is a polyphenol dietary derived from turmeric with numerous pharmacological activities. Recent in vitro and in vivo studies have indicated that curcumin exerted lipid-lowering effects, and also can modulate function of different macrophage subsets in various macrophage-involved diseases. The current review aimed to present role of macrophage subtypes in atherosclerosis development and progression, and to understand effect of curcumin on macrophage polarization and foam cell formation in the atherosclerosis lesions. Overall, we would address important targets for macrophage modulation in atherosclerotic plaques. © 2019, Springer Science+Business Media, LLC, part of Springer Nature