Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

OPTICAL MEASUREMENT OF A TEMPERATURE OF AN OBJECT, AND ASSOCIATED CARTOGRAPHY

The subject of the present invention relates to an optical process for measuring a variation in the temperature of an abject (0), comprising: an emitting step (Sl) consisting in emitting, in the direction of said abject (0), a first incident terahertz elec - tromagnetic wave (Wl_inc), and a measuring step (S2) comprising measuring (S2_3), using a sensor sensitive to terahertz radiation (20), a variation in the amplitude of the electromagnetic radiation of a second electromagnetic wave (W2_ref, W2_tra) in order to determine the variation in the temperature of said abject (0).The subject of the present invention relates to an optical process for measuring a variation in the temperature of an abject (0), comprising: an emitting step (Sl) consisting in emitting, in the direction of said abject (0), a first incident terahertz elec - tromagnetic wave (Wl_inc), and a measuring step (S2) comprising measuring (S2_3), using a sensor sensitive to terahertz radiation (20), a variation in the amplitude of the electromagnetic radiation of a second electromagnetic wave (W2_ref, W2_tra) in order to determine the variation in the temperature of said abject (0)

Antimicrobial and antioxidant activities of cactus polyphenols extract on seafood preservation

The present work investigated the antimicrobial and antioxidant activities of polyphenols extracted from cactus (Opuntia ficus indica) fruit-peels on sardine fillets during refrigerated storage. Biochemical, microbiological and sensorial indicators of treated sardine fillets; were studied comparatively to control lot. Microbial communities were characterized using phenotyping and molecular identification of bacterial isolates; and culture-independent method (PCR-TTGE) for fingerprinting of bacterial DNA extracted from fillets. A principal component analysis (PCA) of all the studied descriptors and variables revealed that discrimination along first principal component (PC1) was mainly correlated positively with peroxidation level and storage time but negatively with polyphenol treatment while along second component (PC2) it was mainly positively correlated to polyphenols treatment and polyene index; confirming the effect of treatment on preservation of sardine fillets. Sensory data studied by the correspondence factorial analysis (CFA) revealed that the addition polyphenols extract extended the shelf life of sardines without altering their sensorial properties. Cactus fruit-peels appeared a promising source of natural bio-preservative agent for aquatic food processing

Apremilast in Combination with Narrowband UVB in the Treatment of Vitiligo: A 52-Week Monocentric Prospective Randomized Placebo-Controlled Study

International audienceBackground: Scientific rationale and encouraging first clinical results suggest the interest of using apremilast for treating vitiligo.Objective: This study aimed to compare the efficacy of apremilast in combination therapy with narrowband (NB)-UVB versus placebo and NB-UVB treatment for repigmentation in patients with nonsegmental vitiligo.Design: This was a 52-week prospective randomized placebo-controlled study.Participants: Adult patients with vitiligo participated.Interventions: Group A received, in addition to phototherapy, apremilast at the label dosage, and group B received placebo. After 24 weeks, patients who responded (decreased Vitiligo Area Scoring Index >30%) were rerandomized to receive apremilast or placebo, combined with twice-weekly NB-UVB for 24 additional weeks. Main outcome and measure: The primary outcome measure was the comparison between the two groups of the Vitiligo Area Scoring Index score at 24 weeks.Results: Eighty patients were randomized (40 in each group). After 24 weeks, the mean Vitiligo Area Scoring Index score decreased from 23.63 to 19.49 (P = 0.011) in the apremilast + UVB group and from 21.57 to 15.25 (P < 0.0001) in the placebo + UVB group. The difference between the two groups was not statistically significant (P = 0.18). No statistically significant differences were observed between the two groups after an additional 24 weeks of treatment.Conclusions and relevance: Apremilast does not bring any benefit to NB-UVB for treating vitiligo.Trial registration: ClinicalTrials.gov NCT03036995

Electro-coagulation of reactive textile dyes and textile wastewater

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TNFα counteracts interleukin-10 anti-inflammatory pathway through the NOX2-Lyn-SHP-1 axis in human monocytes

TNFα-mediated signaling pathways play a pivotal role in the pathogenesis of inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) by promoting phagocyte inflammatory functions, notably cytokine release and reactive oxygen species (ROS) production by NOX2. In contrast, interleukin-10 (IL-10), a powerful anti-inflammatory cytokine, potently shuts down phagocyte activation, making IL-10 an attractive therapeutic candidate. However, IL-10 therapy has shown limited efficacy in patients with inflammatory diseases. Here, we report that TNFα blocks IL-10 anti-inflammatory pathways in human monocytes, thereby prolonging inflammation. TNFα decreased IL-10-induced phosphorylation of STAT3 and consequently IL-10-induced expression of the major anti-inflammatory factor, SOCS3. Decreased STAT3 phosphorylation was due to a SHP1/2 phosphatase, as NSC-87877, a SHP1/2 inhibitor, restored STAT3 phosphorylation and prevented the TNFα-induced inhibition of IL-10 signaling. TNFα activated only SHP1 in human monocytes and this activation was NOX2-dependent, as diphenyleneiodonium, a NOX2 inhibitor, suppressed SHP1 activation and STAT3 dephosphorylation triggered by TNFα. ROS-induced activation of SHP1 was mediated by the redox-sensitive kinase, Lyn, as its inhibition impeded TNFα-induced SHP1 activation and STAT3 dephosphorylation. Furthermore, H2O2 recapitulated TNFα-inhibitory activity on IL-10 signaling. Finally, NSC-87877 dampened collagen antibody-induced arthritis (CAIA) in mice. These results reveal that TNFα disrupts IL-10 signaling by inducing STAT3 dephosphorylation through a NOX2-ROS-Lyn-SHP1 axis in human monocytes and that inhibition of SHP1/2 in vivo protects against CAIA. These new findings might explain the poor efficacy of IL-10 therapy in patients with inflammatory diseases and suggest that anti-TNFα agents and SHP1/2 inhibitors could improve the therapeutic use of IL-10

The caspase-cleaved form of LYN mediates a psoriasis-like inflammatory syndrome in mice.

International audienceWe showed previously that Lyn is a substrate for caspases, a family of cysteine proteases, involved in the regulation of apoptosis and inflammation. Here, we report that expression of the caspase-cleaved form of Lyn (LynDeltaN), in mice, mediates a chronic inflammatory syndrome resembling human psoriasis. Genetic ablation of TNF receptor 1 in a LynDeltaN background rescues a normal phenotype, indicating that LynDeltaN mice phenotype is TNF-alpha-dependent. The predominant role of T cells in the disease occurring in LynDeltaN mice was highlighted by the distinct improvement of LynDeltaN mice phenotype in a Rag1-deficient background. Using pan-genomic profiling, we also established that LynDeltaN mice show an increased expression of STAT-3 and inhibitory members of the NFkappaB pathway. Accordingly, LynDeltaN alters NFkappaB activity underlying a link between inhibition of NFkappaB and LynDeltaN mice phenotype. Finally, analysis of Lyn expression in human skin biopsies of psoriatic patients led to the detection of Lyn cleavage product whose expression correlates with the activation of caspase 1. Our data identify a new role for Lyn as a regulator of psoriasis through its cleavage by caspases

Protein Kinase CK2 Acts as a Molecular Brake to Control NADPH Oxidase 1 Activation and Colon Inflammation

International audienceBACKGROUND & AIMS: NADPH oxidase 1 (NOX1) has emerged as a prime regulator of intestinal mucosa immunity and homeostasis. Dysregulation of NOX1 may cause inflammatory bowel disease (IBD). It is not clear how NOX1 is regulated in vivo under inflammatory conditions. We studied the role of CK2 in this process.METHODS: The NOX1 organizer subunit, NADPH oxidase organizer 1 (NOXO1), was immunoprecipitated from cytokine-treated colon epithelial cells, and bound proteins were identified by mass spectrometry analysis. Sites on NOXO1 phosphorylated by CK2 were identified by nanoscale liquid chromatography coupled to tandem mass spectrometry. NOX1 activity was determined in colon epithelial cells and colonoids in the presence or absence of CX-4945, a CK2 specific inhibitor. Acute colitis was induced by administration of trinitrobenzenesulfonic acid in mice treated or not with CX-4945. Colon tissues were analyzed by histologic examination, quantitative polymerase chain reaction, and Western blots. CK2 activity, markers of inflammation, and oxidative stress were assessed.RESULTS: We identified CK2 as a major partner of NOXO1 in colon epithelial cells under inflammatory conditions. CK2 directly binds NOXO1 at the C-terminus containing the Phox homology domain and phosphorylates NOXO1 on several sites. CX-4945 increased ROS generation by NOX1 in human colon epithelial cells and organoids. Strikingly, CK2 activity was reduced in trinitrobenzenesulfonic acid-induced acute colitis, and CX-4945 exacerbated colitis inflammation as shown by increased levels of CXCL1, ROS generation, lipid peroxidation, and colon damage.CONCLUSIONS: The ubiquitous protein kinase CK2 limits NOX1 activity via NOXO1 binding and phosphorylation in colonic epithelial cells and lessens experimental colitis. Loss of CK2 activity during acute colitis results in excessive ROS production, contributing to the pathogenesis. Strategies to activate CK2 could be an effective novel therapeutic approach in IBD

The burden of chronic spontaneous urticaria: unsatisfactory treatment and healthcare resource utilization in France (the ASSURE-CSU study)

International audienceData on the clinical burden of chronic spontaneous urticaria (CSU) and economic consequences are lacking in France. To characterize the clinical and economic burden of CSU in symptomatic patients despite treatment by analysing data of French patients from the ASSURE-CSU study. ASSURE-CSU was an international observational study that included CSU patients with symptoms that lasted for 12 months or more despite treatment. Disease characteristics and healthcare resource use were obtained from medical records. Data on disease history, health-related quality of life (HR-QoL), and work productivity were collected from a patient survey. A total of 101 patients were analysed (76.2% female; mean age: 48.9 years) with moderate to severe disease (UAS7 score ≥16) in 43.4% and angioedema in 72.3%. The mean (S.D.) total scores of Chronic Urticaria Quality of Life (CU-QoL) and Dermatology Life Quality Index (DLQI) were 37.7 (22.3) and 9.7 (6.9), respectively, thus indicating a significant impact of the disease on HR-QoL. Mean absenteeism and presenteeism were 6.4% and 20.8%, respectively, with a mean loss of work productivity estimated at 20.7%. The mean (S.D.) total direct cost of CSU was €2,397 per patient per year and was mainly driven by therapies (€1,435) and inpatient costs (€859). The indirect costs for four weeks were mainly presenteeism (€421) and loss of work productivity (€420). CSU significantly impairs HR-QoL, which increases with the severity of the disease. The direct and indirect costs for the management of symptomatic CSU are an important economic burden.</p

NOX1-derived ROS drive the expression of Lipocalin-2 in colonic epithelial cells in inflammatory conditions

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