An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Obesity is associated with a significantly increased risk for cancer suggesting that adipose tissue dysfunctions might play a crucial role therein. Macrophages play important roles in adipose tissue as well as in cancers. Here, we studied whether human adipose tissue macrophages (ATM) modulate cancer cell function. Therefore, ATM were isolated and compared with monocyte-derived macrophages (MDM) from the same obese patients. ATM, but not MDM, were found to secrete factors inducing inflammation and lipid accumulation in human T47D and HT-29 cancer cells. Gene expression profile comparison of ATM and MDM revealed overexpression of functional clusters, such as cytokine-cytokine receptor interaction (especially CXC-chemokine) signaling as well as cancer-related pathways, in ATM. Comparison with gene expression profiles of human tumor-associated macrophages showed that ATM, but not MDM resemble tumor-associated macrophages. Indirect co-culture experiments demonstrated that factors secreted by preadipocytes, but not mature adipocytes, confer an ATM-like phenotype to MDM. Finally, the concentrations of ATM-secreted factors related to cancer are elevated in serum of obese subjects. In conclusion, ATM may thus modulate the cancer cell phenotype.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

We investigated the clinical significance of plasma interleukin (IL)-6, IL-1, IL-1 decoy receptor and pentraxin 3 (PTX3) levels in chronic heart failure (CHF) patients with or without chronic obstructive pulmonary disease (COPD). Plasma levels of these inflammatory markers were measured by using a sandwich enzyme-linked immunosorbent assay in 118 patients. Subjects were ≥65 years, ≥10 pack-years, with a new diagnosis of CHF. The prevalence of COPD was 30% (36/118). Only 2/118 patients had previously diagnosed COPD. The percent of patients given β-blockers (80% vs 89%, P = 0.1), and the optimized to CHF target dose of β-blockers (46.3% vs 59.7%, P = 0.1) were no different in patients with or without COPD. Subjects were prospectively followed for 357 (336-364) days with the end point of death or all-cause hospitalization (adverse event). Baseline plasma levels of IL-6, IL-1, IL-1 decoy receptor and PTX3 were comparable between CHF patients with and without COPD. None of the inflammatory markers correlated with CHF severity. Death or hospitalization occurred in 70 (59.3%) patients. High IL-6 levels was a significant independent predictor for adverse event (WALD CHI-SQUARE P=0.0083), whereas IL-1, IL-1 decoy receptor and PTX3 were not. IL-6 levels correlated positively with high-sensitive C-reactive protein (hs-CRP) levels (r = 0.67, p < 0.0001), although hs-CRP was not associated with death or hospitalization. These results suggest that plasma levels of IL-6 might serve as a prognostic markers in short-term prognosis of elderly CHF patients either with or without COPD.

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease and is characterized by the degeneration of upper and lower motor neurons. It has become increasingly clear that RNA dysregulation is a key contributor to ALS pathogenesis. The major ALS genes <i>SOD1, TARDBP, FUS</i>, and <i>C9orf72</i> are involved in aspects of RNA metabolism processes such as mRNA transcription, alternative splicing, RNA transport, mRNA stabilization, and miRNA biogenesis. In this review, we highlight the current understanding of RNA dysregulation in ALS pathogenesis involving these major ALS genes and discuss the potential of therapeutic strategies targeting disease RNAs for treating ALS.

Abstract Primary Subject area Mental Health Background The transition from high school to postsecondary is a critical milestone for independence and empowerment. This life stage frequently coincides with the emergence of most mental health conditions (MHCs). Without adequate support to assist with the transition to postsecondary education, the mental health of arriving students with existing MHCs is likely to decline or remain unmet. Declining mental health is strongly associated with students withdrawing from both secondary and postsecondary education. However, a scoping review of interventions aiming to support youth with MHCs transition to postsecondary has not been conducted. Objectives The objectives of this scoping review were to identify: (1) researched interventions that support youth with MHCs during the transition to postsecondary; (2) best practices used to support this transition; (3) methods of evaluating these interventions and any limitations; and (4) gaps where future research is warranted. Design/Methods A database search of MEDLINE, PsycINFO, Embase, SocINDEX, ERIC, CINHAL, and Education Research Complete was undertaken. Two reviewers independently screened studies and extracted the data. Thematic analysis and risk-of-bias assessment were conducted on included studies. Results Nine studies were included in this review, describing eight unique interventions (Figure 1). Sixty-two percent of interventions were nonspecific in the MHCs that they were targeting in postsecondary students. These interventions were designed to support students upon arrival to postsecondary. Peer mentorship, student engagement, and interagency collaboration were found to be beneficial approaches to supporting youth transitioning into postsecondary (Table 1). The overall quality and level of evidence in these studies was low. Three knowledge gaps were found: evidence was not generalizable to the diversity of MHCs, intervention studies were mostly cross-sectional in nature and lacked follow-up data, and sustaining intervention funding remained a challenge for postsecondary institutions. Conclusion The volume of research identified was limited but indicated overall that offering support during the transition to postsecondary was beneficial for students with MHCs. Further evidence is needed that is generalizable across the mental health spectrum, and that assesses intervention outcomes in relation to intervention costs.

Toll interleukin-1 receptor (IL-1R) 8 (TIR8), also known as single Ig IL-1 receptor (IL-R)-related molecule, or SIGIRR, is a member of the IL-1R-like family, primarily expressed by epithelial cells. Current evidence suggests that TIR8 plays a nonredundant role as a negative regulator in vivo under different inflammatory conditions that are dependent on IL-R and Toll-like receptor (TLR) activation. In the present study, we examined the role of TIR8 in innate resistance to acute lung infections caused by Pseudomonas aeruginosa, a Gram-negative pathogen responsible for life-threatening infections in immunocompromised individuals and cystic fibrosis patients. We show that Tir8 deficiency in mice was associated with increased susceptibility to acute P. aeruginosa infection, in terms of mortality and bacterial load, and to exacerbated local and systemic production of proinflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], IL-1β, and IL-6) and chemokines (CXCL1, CXCL2, and CCL2). It has been reported that host defense against P. aeruginosa acute lung infection can be improved by blocking IL-1 since exaggerated IL-1β production may be harmful for the host in this infection. In agreement with these data, IL-1RI deficiency rescues the phenotype observed in Tir8-deficient mice: in Tir8-/- IL-1RI-/- double knockout mice we observed higher survival rates, enhanced bacterial clearance, and reduced levels of local and systemic cytokine and chemokine levels than in Tir8-deficient mice. These results suggest that TIR8 has a nonredundant effect in modulating the inflammation caused by P. aeruginosa, in particular, by negatively regulating IL-1RI signaling, which plays a major role in the pathogenesis of this infectious disease.

We thank Blackwell  et al 1 for raising an important question about the classification of depression in a population of IBD patients in the UK. In our study,examining depression as a risk factor for the development of IBD,2 we chose to use a more restrictive case definition of depression based closely on a definition of major depressive disorder (MDD) as a clinically significant form of depression recognised in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)3 and known to be associated with a significant degree of morbidity and mortality.4 5 In …

One in six persons with IBD experienced an SUD, suggesting that clinicians should maintain high index of suspicion regarding possible SUD, and inquiries about substance use should be a part of care for IBD patients, particularly for men, smokers, and patients with anxiety disorders and pain.