Prevalence and risk factors of sleep disorders in inflammatory bowel disease: a cross-sectional study.

BACKGROUND: Sleep disorders are one of the major public health problems, which can potentially induce inflammation and exacerbate disease activity, resulting in compromised sleep quality. This study aimed to investigate the prevalence and risk factors associated with sleep disorders among patients with inflammatory bowel disease (IBD). METHODS: Between March 2023 and February 2024, the Pittsburgh Sleep Quality Index was employed to assess sleep quality in both IBD patients and healthy control subjects. Univariate and multivariate analysis were performed to identify the risk factors associated with SD in IBD patients. RESULTS: Overall, 208 IBD patients [150 Crohn's disease (CD) and 58 ulcerative colitis (UC)] and 199 healthy individuals were included. Sleep disorders were observed in 59.6% of patients with IBD, with a higher prevalence among females (63.5%) compared to males (56.9%) (P = 0.476). The prevalence of sleep disorders in IBD patients was significantly higher than that found in healthy controls (37.7%) (all P < 0.01). The prevalence of sleep disorders  among CD and UC patients was 58% and 63.8%, respectively (P = 0.291). The multivariate analysis revealed that older age (OR, 1.070; 95% CI: 1.035-1.105, P = 0.000), smoking (OR, 2.698; 95% CI: 1.089-6.685, P = 0.032), and depression (OR, 4.779; 95% CI: 1.915-11.928, P = 0.001) were risk factors for sleep disorders in IBD patients. However, higher body mass index (OR, 0.879; 95% CI: 0.790-0.977, P = 0.017) was identified as a protective factor. CONCLUSION: Sleep disorders are common among IBD patients regardless of activity levels. Smoking and depression are the major risk factors.

Structural and Functional Insights into PpgL, a Metal-Independent ß-Propeller Gluconolactonase That Contributes to Pseudomonas aeruginosa Virulence.

Biofilm formation is a critical determinant in the pathopoiesis of Pseudomonas aeruginosa It could significantly increase bacterial resistance to drugs and host defense. Thus, inhibition of biofilm matrix production could be regarded as a promising attempt to prevent colonization of P. aeruginosa and the subsequent infection. PpgL, a periplasmic gluconolactonase, has been reported to be involved in P. aeruginosa quorum-sensing (QS) system regulation. However, the detailed function and catalysis mechanism remain elusive. Here, the crystal structure of PpgL is described in the current study, along with biochemical analysis, revealing that PpgL is a typical ß-propeller enzyme with unique metal-independent lactone hydrolysis activity. Consequently, comparative analysis of seven-bladed propeller lactone-catalyzing enzymes and mutagenesis studies identify the critical sites which contribute to the diverse catalytic and substrate recognition functions. In addition, the reduced biofilm formation and attenuated invasion phenotype resulting from deletion of ppgL confirm the importance of PpgL in P. aeruginosa pathogenesis. These results suggest that PpgL is a potential target for developing new agents against the diseases caused by P. aeruginosa.

Mechanistic insights into the allosteric regulation of Pseudomonas aeruginosa aspartate kinase.

In plants and microorganisms, aspartate kinase (AK) catalyzes an initial commitment step of the aspartate family amino acid biosynthesis. Owing to various structural organizations, AKs from different species show tremendous diversity and complex allosteric controls. We report the crystal structure of AK from Pseudomonas aeruginosa (PaAK), a typical α2ß2 hetero-tetrameric enzyme, in complex with inhibitory effectors. Distinctive features of PaAK are revealed by structural and biochemical analyses. Essentially, the open conformation of Lys-/Thr-bound PaAK structure clarifies the inhibitory mechanism of α2ß2-type AK. Moreover, the various inhibitory effectors of PaAK have been identified and a general amino acid effector motif of AK family is described.

Structure-Function Relationship of Aminopeptidase P from Pseudomonas aeruginosa.

PepP is a virulence-associated gene in Pseudomonas aeruginosa, making it an attractive target for anti-P. aeruginosa drug development. The encoded protein, aminopeptidases P (Pa-PepP), is a type of X-prolyl peptidase that possesses diverse biological functions. The crystal structure verified its canonical pita-bread fold and functional tetrameric assembly, and the functional studies measured the influences of different metal ions on the activity. A trimetal manganese cluster was observed at the active site, elucidating the mechanism of inhibition by metal ions. Additionally, a loop extending from the active site appeared to be important for specific large-substrate binding. Based on the structural comparison and bacterial invasion assays, we showed that this non-conserved surface loop was critical for P. aeruginosa virulence. Taken together, these findings can extend our understanding of the catalytic mechanism and virulence-related functions of Pa-PepP and provide a solid foundation for the design of specific inhibitors against pathogenic-bacterial infections.