Graves' orbitopathy (GO), also known as thyroid eye disease, affects approximately 3 million people in Europe with an estimated socioeconomic burden of 6.4 billion euros per annum. GO is a complication of Graves' disease which is an autoimmune disease and the commonest cause of an overactive thyroid gland. The treatment of GO remains unsatisfactory and the majority of patients report long-term impairment of quality of life. The effects of gut derived antigens, from micro-organisms and nutrients, on the autoimmune response will be tested in the animal model by probiotic and "contra-biotic" intervention. In the Indigo interventional trial the investigators will add to the standard anti-thyroid drug treatment (ATD) a specifically designed probiotics (LAB4, Cultech Ltd., West Glamorgan, UK) to assess whether it is possible to modify the microbiome in GD patients and improve their immunological status.

开始日期2015-02-01

申办/合作机构

Fondazione IRCCS Ca' Granda

[+2]

100 项与 LAB4 相关的临床结果

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100 项与 LAB4 相关的转化医学

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100 项与 LAB4 相关的专利（医药）

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项与 LAB4 相关的文献（医药）

2024-06-01·International Journal of Biological Macromolecules

Identifying and characterization of novel broad-spectrum bacteriocins from the Shanxi aged vinegar microbiome: Machine learning, molecular simulation, and activity validation

Article

作者: Wang, Min ; Zhang, Xiaofeng ; Cui, Meili ; Wang, Mengyue ; Xia, Menglei ; Sun, Haoyan ; Su, Zhenhua ; Yu, Lu ; Zheng, Yu ; Shen, Yanbing

Shanxi aged vinegar microbiome encodes a wide variety of bacteriocins. The aim of this study was to mine, screen and characterize novel broad-spectrum bacteriocins from the large-scale microbiome data of Shanxi aged vinegar through machine learning, molecular simulation and activity validation. A total of 158 potential bacteriocins were innovatively mined from 117,552 representative genes based on metatranscriptomic information from the Shanxi aged vinegar microbiome using machine learning techniques and 12 microorganisms were identified to secrete bacteriocins at the genus level. Subsequently, employing AlphaFold2 structure prediction and molecular dynamics simulations, eight bacteriocins with high stability were further screened, and all of them were confirmed to have bacteriostatic activity by the Escherichia coli BL21 expression system. Then, gene_386319 (named LAB-3) and gene_403047 (named LAB-4) with the strongest antibacterial activities were purified by two-step methods and analyzed by mass spectrometry. The two bacteriocins have broad-spectrum antimicrobial activity with minimum inhibitory concentration values of 6.79 μg/mL-15.31 μg/mL against Staphylococcus aureus and Escherichia coli. Furthermore, molecular docking analysis indicated that LAB-3 and LAB-4 could interact with dihydrofolate reductase through hydrogen bonds, salt-bridge forces and hydrophobic forces. These findings suggested that the two bacteriocins could be considered as promising broad-spectrum antimicrobial agents.

2021-11-01·Genomics3区 · 生物学

A genome guided evaluation of the Lab4 probiotic consortium

3区 · 生物学

Article

作者: Hughes, T R ; Allen, M D ; Plummer, S F ; Masetti, G ; Jack, A A ; Baker, L M ; Marchesi, J R ; Del Sol, R ; Facey, P D ; Michael, D R ; Ramanathan, G ; Webberley, T S ; Joyce, T S C

Draft genome sequences of the Lab4 probiotic consortium were deposited in Genbank: Bifidobacterium animalis subsp lactis CUL34 (PRJNA482550), Bifidobacterium bifidum CUL20 (PRJNA559984), Lactobacillus acidophilus CUL60 (PRJNA482335), Lactobacillus acidophilus CUL21 (PRJNA482434). Probiogenomic analyses confirmed existing taxonomies and identified putative gene sequences that were functionally related to the performance of each organism during in vitro assessments of bile and acid tolerability, adherence to enterocytes and susceptibility to antibiotics. Genomic stability predictions identified no significant risk of gene acquisition of both antibiotic resistance and virulence genes. These observations were supported by acute phase and repeat dose tolerability studies in Wistar rats. High doses of Lab4 did not result in mortalities, clinical/histopathological abnormalities nor systemic toxicity. Increased faecal numbers of Lab4 in supplemented rats implied survival through the gastrointestinal tract and/or impact the intestinal microbiota composition. In summary, this study provides multifaceted support for probiotic functionality and the safety of the Lab4 consortium.

2019-04-19·Beneficial Microbes3区 · 医学

In vitro neuroprotective activities of two distinct probiotic consortia

3区 · 医学

Article

作者: Allen, M.D. ; Loxley, K.E. ; Plummer, S.F. ; Davies, T.S. ; Hughes, T.R. ; Good, M.A. ; Michael, D.R.

Neurodegeneration has been linked to changes in the gut microbiota and this study compares the neuroprotective capability of two bacterial consortia, known as Lab4 and Lab4b, using the established SH-SY5Y neuronal cell model. Firstly, varying total antioxidant capacities (TAC) were identified in the intact cells from each consortia and their secreted metabolites, referred to as conditioned media (CM). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Crystal Violet (CV) assays of cell viability revealed that Lab4 CM and Lab4b CM could induce similar levels of proliferation in SH-SY5Y cells and, despite divergent TAC, possessed a comparable ability to protect undifferentiated and retinoic acid-differentiated cells from the cytotoxic actions of rotenone and undifferentiated cells from the cytotoxic actions of 1-methyl-4-phenylpyridinium iodide (MPP+). Lab4 CM and Lab4b CM also had the ability to attenuate rotenone-induced apoptosis and necrosis with Lab4b inducing the greater effect. Both consortia showed an analogous ability to attenuate intracellular reactive oxygen species accumulation in SH-SY5Y cells although the differential upregulation of genes encoding glutathione reductase and superoxide dismutase by Lab4 CM and Lab4b CM, respectively, implicates the involvement of consortia-specific antioxidative mechanisms of action. This study implicates Lab4 and Lab4b as potential neuroprotective agents and justifies their inclusion in further in vivo studies.

100 项与 LAB4 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
格雷夫斯眼病	临床2期	意大利	Cultech Ltd.	2015-02-01
格雷夫斯眼病	临床2期	意大利	Fondazione IRCCS Ca' Granda	2015-02-01
老年性骨发育不良	临床2期	意大利	Fondazione IRCCS Ca' Granda	-