Burtondoyle6125

idates in monotherapy that, in the presence of radiotherapy, would make it through clinical trials.The intestinal microbiota influences the development and function of the mucosal immune system. However, the exact mechanisms by which commensal microbes modulate immunity is not clear. We previously demonstrated that commensal Bacteroides ovatus ATCC 8384 reduces mucosal inflammation. Herein, we aimed to identify immunomodulatory pathways employed by B. ovatus. In germ-free mice, mono-association with B. ovatus shifted the CD11b+/CD11c+ and CD103+/CD11c+ dendritic cell populations. Because indole compounds are known to modulate dendritic cells, B. ovatus cell-free supernatant was screened for tryptophan metabolites by liquid chromatography-tandem mass spectrometry and larger quantities of indole-3-acetic acid were detected. Analysis of cecal and fecal samples from germ-free and B. ovatus mono-associated mice confirmed that B. ovatus could elevate indole-3-acetic acid concentrations in vivo. Indole metabolites have previously been shown to stimulate immune cells to secrete the reparative cytokine IL-22. Addition of B. ovatus cell-free supernatant to immature bone marrow-derived dendritic cells stimulated IL-22 secretion. The ability of IL-22 to drive repair in the intestinal epithelium was confirmed using a physiologically relevant human intestinal enteroid model. Finally, B. ovatus shifted the immune cell populations in trinitrobenzene sulfonic acid-treated mice and up-regulated colonic IL-22 expression, effects that correlated with decreased inflammation. Our data suggest that B. ovatus-produced indole-3-acetic acid promotes IL-22 production by immune cells, yielding beneficial effects on colitis.Multiple myeloma (MM) progression closely depends on bone marrow (BM) angiogenesis. Several factors sustain angiogenesis, including cytokines, growth factors, and cell-to-cell interactions. Herein, BM thrombopoietin (TPO) was shown to support angiogenesis and disease progression in MM. Patients with MM at different progression phases had higher levels of BM and circulating TPO than monoclonal gammopathy of undetermined significance/smoldering MM patients, suggesting that TPO correlates with disease progression and prognosis. Endothelial cells from patients with monoclonal gammopathy of undetermined significance (MGECs) and endothelial cells from MM (MMECs) expressed TPO receptor, and the TPO treatment triggered their angiogenic capabilities in vitro. Indeed, TPO-treated MGECs and MMECs showed enhanced angiogenesis on Matrigel and spontaneous cell migration and chemotaxis by acting as a chemotactic agent. TPO also had an angiogenic activity in vivo in the chorioallantoic membrane assay system. Finally, TPO treatment increased the release of active matrix metalloproteinase (MMP)-9 and MMP-2 in MGECs and of MMP-2 in MMECs and affected the balance between angiogenic/antiangiogenic factors in the MM BM. Our results support the angiogenic activity of TPO, and suggest that it may have a critical role in promoting the angiogenic switch during MM progression. Accordingly, TPO may be envisaged as a new angiogenic and prognostic factor in patients with MM.Infantile hypercalcemia (IH), is a rare disorder caused by CYP24A1 or SLC34A1 variants which lead to disturbed catabolism of 25(OH)D3 and 125(OH)2D3 or increased generation of 125(OH)2D3.

To assess the status of 2425(OH)

D

and other markers of vitamin D in IH survivors, in whom variants of CYP24A1 or SLC34A1 gene were found and to compare these unique biochemical features with those obtained from subjects who were diagnosed in the first year of life with hypercalcemia, elevated 25(OH)D

and low PTH but in whom neither CYP24A1 nor SLC34A1 variant was found.

16 IH survivors in whom CYP24A1 (n = 13) or SLC34A1 (n = 3) variants were found and 41 subjects in whom hypercalcemia was diagnosed in the first year of life but in whom CYP24A1 or SLC34A1 variants were not found were included in the study. Ipatasertib clinical trial 25(OH)D

, 3-epi-25(OH)D

, 25(OH)D

, 2425(OH)

D

were assessed by liquid chromatography coupled with tandem mass spectrometry. 125(OH)

D

concentrations were assessed by chemiluminescence.

Subjects with CYP24A1 variants, despite normal 25(OH)D

levels, had higher 25(OH)D

/2425(OH)

D

ratio values (487; 265-1073 ng/mL) when compared to subjects with SLC34A1 variants (16; 16-23 ng/mL) and with subjects in whom CYP24A1 or SLC34A1 were not found (56; 9-56 ng/mL) (p = 0.00003). Separation of interfering metabolite further increased differences between subjects with and without CYP24A1 mutation.

Survivors of IH with CYP24A1 variant, despite being normocalcemic, still presented extremely high 25(OH)D

/2425(OH)

D

ratio values. Separation of interfering compound further increased differences between subjects with CYP24A1 mutation and without this mutation.

Survivors of IH with CYP24A1 variant, despite being normocalcemic, still presented extremely high 25(OH)D3/2425(OH)2D3 ratio values. Separation of interfering compound further increased differences between subjects with CYP24A1 mutation and without this mutation.

The inferior phrenic artery is a paired artery that supplies the diaphragm from its inferior aspect. It may arise as a common trunk, the common inferior phrenic artery (CIPA), or as two individual arteries, the right and left inferior phrenic arteries (RIPA and LIPA, respectively). The aim of this study was to perform a systematic review and meta-analysis to create pooled prevalence data on the various origins of the inferior phrenic arteries and to discuss their clinical importance.

Major electronic medical databases were reviewed to identify articles with anatomical prevalence data on the origin of the inferior phrenic arteries. Data on the origin of the left, right and common inferior phrenic arteries were extracted and quantitatively synthesized.

The CIPA was present in 24.2% of cases and most commonly originated from the aorta, with a pooled prevalence 57.2% (95% CI 52.4-62.0%), and the coeliac trunk, with a pooled prevalence of 41.3% (95% CI 36.8-45.9%). Other origins were much less common (1.00% (95% CI 0.