Yokukansan, a Traditional Japanese Medicine, Enhances the Glutamate Transporter GLT-1 Function in Cultured Rat Cortical Astrocytes

Astrocytes carry two glutamate transporters—GLAST and GLT-1—the latter of which is responsible for >90% of glutamate uptake activity in the brain; however, under culture conditions, the GLT-1 expression in astrocytes is exceedingly low, as is the glutamate uptake activity mediated by GLT-1. This study aimed to elucidate the effects of yokukansan (YKS) in relation to the GLT-1-mediated regulation of extracellular glutamate concentrations. Thus, we treated cultured astrocytes with tumor necrosis factor-α (TNF-α) and dibutyryl-cAMP (dBcAMP) (hereinafter, referred to as "TA") to increase GLT-1 expression and then functionally examined how YKS would affect glutamate uptake ability derived from GLT-1. Contrary to expectations, although the TA treatments did not affect the uptake activity, YKS significantly augmented it. Conversely, GLAST-derived glutamate uptake was significantly reduced by TA treatments but was unaffected by YKS. Subsequently, we analyzed the GLT-1 protein and mRNA levels and found that TA treatments had significantly increased them, which were then further augmented by YKS. These findings suggest that YKS enhances GLT-1-derived glutamate transport functions in TA-treated cultured astrocytes and that this process entails increased GLT-1 protein and mRNA levels. This type of mechanism may contribute to the YKS-mediated regulation of extracellular glutamate concentrations.

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Toxicological Evaluation of Essential Oils from Some Plants of Rutaceae Family

Essential oils are produced as secondary metabolites by aromatic plants, predominantly belonging to families Apiaceae, Lamiaceae, Myrtaceae, and Rutaceae. The family Rutaceae has great economic importance for its numerous edible fruits and essential oils. In the present study, essential oils of seven plants of family Rutaceae, Aegle marmelos, Murraya koenigii, Citrus reticulata Blanco, Zanthoxylum armatum, Skimmia laureola, Murraya paniculata, and Boenninghausenia albiflora, were used for their toxicological assessment. Seven groups of selected essential oils-treated Wistar rats were established against control group () that received water for 14 days; animals were offered feed and water ad libitum and treated with essential oils at 400 mg/kg body weight. Hematological studies revealed significant elevation in TEC in animals treated with essential oils of M. koenigii, S. laureola, and B. albiflora, while an elevation in PCV and depletion in MCV were observed in animals treated with M. paniculata and B. albiflora, respectively. Serological investigations demonstrated significant depletion in triglycerides and elevation in blood sodium level in animals treated with essential oils of A. marmelos and C. reticulata Blanco. Boenninghausenia albiflora affected many markers including RBC, MCV, triglycerides, HDL, LDL, urea, and sodium. In conclusion, all oils except B. albiflora can be considered safe for internal use.

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Shaping a universally broad antibody response to influenza amidst a variable immunoglobulin landscape

Sarah F Andrews | Adrian B McDermott

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Influenza vaccines: ‘tailor-made’ or ‘one fits all’

Giulietta Saletti | Thomas Gerlach | Guus F Rimmelzwaan

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Immune evasion of the CD1d/NKT cell axis

Randy R Brutkiewicz | Laura Yunes-Medina | Jianyun Liu

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Elective endoscopic clipping for the treatment of symptomatic diverticular disease: a potential for 'cure

Message

Symptomatic diverticular disease (DD) is a major worldwide healthcare burden, and diverticular bleeding is one of its most common manifestations. Endoscopic clipping of selected diverticula in the acute or early posthaemorrhage period has been reported as a haemostatic intervention, but the effect of elective clipping is not known.

We present the prospective series of elective endoscopic clipping with the aim of treating all visible diverticula in patients with previous bleeding, resulting in near-complete disappearance of DD.

This may have significant implications for the management of DD worldwide and warrants further prospective research.

In more detail

This was a prospective, single-centre study enrolling consecutive patients attending a specialist DD clinic at our institution, who had been previously hospitalised for lower GI bleeding due to DD (table 1). The procedures and follow-up colonoscopies were carried out from April 2015 to April 2017 at King's College Hospital, London, UK. Patients with other GI pathologies...

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Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease

Objective

Vedolizumab, a monoclonal antibody directed against the integrin heterodimer α4β7, is approved for the treatment of Crohn's disease and ulcerative colitis. The efficacy of vedolizumab has been suggested to result from inhibition of intestinal T cell trafficking although human data to support this conclusion are scarce. We therefore performed a comprehensive analysis of vedolizumab-induced alterations in mucosal and systemic immunity in patients with inflammatory bowel disease (IBD), using anti-inflammatory therapy with the TNFα antibody infliximab as control.

Design

Immunophenotyping, immunohistochemistry, T cell receptor profiling and RNA sequencing were performed using blood and colonic biopsies from patients with IBD before and during treatment with vedolizumab (n=18) or, as control, the anti-TNFα antibody infliximab (n=20). Leucocyte trafficking in vivo was assessed using single photon emission computed tomography and endomicroscopy.

Results

Vedolizumab was not associated with alterations in the abundance or phenotype of lamina propria T cells and did not affect the mucosal T cell repertoire or leucocyte trafficking in vivo. Surprisingly, however, α4β7 antibody treatment was associated with substantial effects on innate immunity including changes in macrophage populations and pronounced alterations in the expression of molecules involved in microbial sensing, chemoattraction and regulation of the innate effector response. These effects were specific to vedolizumab, not observed in response to the TNFα antibody infliximab, and associated with inhibition of intestinal inflammation.

Conclusion

Our findings suggest that modulation of innate immunity contributes to the therapeutic efficacy of vedolizumab in IBD.

Trial registration number

NCT02694588

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