Role and new insights of microfibrillar-associated protein 4 in fibrotic diseases.

Fibrosis is one of the most worrisome complications of chronic inflammatory diseases, leading to tissue damage, organ failure, and ultimately, death. The most notable pathological characteristic of fibrosis is the excessive accumulation of extracellular matrix (ECM) components such as collagen and fibronectin adjacent to foci of inflammation or damage. The human microfibrillar-associated protein 4 (MFAP4), an important member of the superfamily of fibrinogen-related proteins, is considered to have an extremely important role in ECM transformation of fibrogenesis. This review summarizes the structure, characteristics, and physiological functions of MFAP4 and the importance of MFAP4 in various fibrotic diseases. Meanwhile, we elaborated the underlying actions and mechanisms of MFAP4 in the development of fibrosis, suggesting that a better understand of MFAP4 broadens novel perspective for early screening, diagnosis, prognostic risk assessment, and treatment of fibrotic diseases.

Association of Sleep Duration with Tooth Loss and Periodontitis: Insights from the National Health and Nutrition Examination Surveys (2005-2020).

OBJECTIVE: Sleep disorders such as insomnia, apnea, and restless leg syndrome can negatively affect a person's overall health and may cause hypertension, heart failure, and coronary heart disease. Likewise, periodontitis, a gum disease, can lead to both physical and psychological health issues, exerting a considerable effect on one's overall well-being-periodontitis stands as a primary cause of tooth loss. Nevertheless, there has been insufficient research on the correlation between the amount of sleep individuals get and the occurrence of periodontitis/tooth loss among Americans. Therefore, this study aimed to assess the influence of sleep length on periodontitis in the American population. METHODS: Periodontitis severity was classified (none, mild, moderate, and severe) using American Periodontal Association criteria. Sleep duration was assessed by self-reported data and categorized into three groups (deficient, adequate, and excessive). Tooth loss was assessed by the oral examination. To establish a connection between the duration of sleep and periodontitis/tooth loss, a weighted multivariable logistic regression analysis was employed. A GAM analysis and smooth curve fitting assessment were conducted to identify non-linear relationships. Subgroup, interaction, and mediation analyses were also performed. RESULTS: The prevalence of tooth loss was significantly high, affecting 96.4% of the individuals, whereas 46.6% of the study sample experienced moderate to severe periodontitis. The average age of participants was 52.7 years. After adjusting for potential confounding factors, the analysis of weighted multivariable logistic regression revealed a significant association between sleep insufficiency and moderate/severe periodontitis (OR 1.15, 95% CI 1.01-1.30, P = 0.0298), as well as tooth loss (OR 1.16, 95% CI 1.01-1.33, P = 0.0371). Additionally, the research showed a correlation between the length of sleep and periodontitis that followed a U-shaped pattern. In addition, the analysis of mediation revealed that high blood pressure explained 7.0% (95% CI 4.0% to 12.9%; P < 0.0001) of the link between the amount of sleep and the likelihood of losing teeth. CONCLUSION: Sleep duration was independently correlated with moderate/severe periodontitis/tooth loss and had a non-linear relationship.

Integrating GWAS and proteome data to identify novel drug targets for MU.

Mouth ulcers have been associated with numerous loci in genome wide association studies (GWAS). Nonetheless, it remains unclear what mechanisms are involved in the pathogenesis of mouth ulcers at these loci, as well as what the most effective ulcer drugs are. Thus, we aimed to screen hub genes responsible for mouth ulcer pathogenesis. We conducted an imputed/in-silico proteome-wide association study to discover candidate genes that impact the development of mouth ulcers and affect the expression and concentration of associated proteins in the bloodstream. The integrative analysis revealed that 35 genes play a significant role in the development of mouth ulcers, both in terms of their protein and transcriptional levels. Following this analysis, the researchers identified 6 key genes, namely BTN3A3, IL12B, BPI, FAM213A, PLXNB2, and IL22RA2, which were related to the onset of mouth ulcers. By combining with multidimensional data, six genes were found to correlate with mouth ulcer pathogenesis, which can be useful for further biological and therapeutic research.

Mortality and Associated Risk Factors in Dialysis Patients with Cardiovascular Disease.

BACKGROUND/AIMS: Although dialysis patients have a higher risk of morbidity and mortality related to cardiovascular disease (CVD) than the general population, the mortality and associated risk factors in Asian dialysis patients with CVD have not been well examined. METHODS: In this prospective cohort study, mortality and risk factors were investigated in 591 dialysis patients who were recruited from two dialysis centers from May 1, 2009 to May 1, 2014. The Cox proportional hazards regression assessed adjusted differences in mortality risk. A multivariate analysis was also performed, comparing the CVD and non-CVD groups. RESULTS: A total of 591 patients were enrolled in this study (mean age, 52.05 ± 16.46 years [SD]; 61.8% men; 20.8% with CVD), with a median follow-up of 21.9 (maximum, 72) months. The cumulative hazard of mortality was significantly higher in CVD patients (hazard ratio [HR], 1.835; 95% confidence interval [CI], 1.023-3.293; P=0.042) than in their non-CVD counterparts after adjusting for various confounders. On multivariate Cox analysis, stroke (HR, 4.574; 95% CI, 2.149-9.736; P<0.001) was an independent predictor of all-cause mortality in the CVD group. In the non-CVD group, diabetes mellitus (HR, 2.974; 95% CI, 1.560-5.668; P=0.001) and elevated high-sensitivity C-reactive lipoprotein (hs-CRP) (HR, 1.017; 95% CI, 1.005-1.030; P=0.005) were independent predictors of all-cause mortality. CONCLUSION: All-cause mortality was significantly higher in the CVD group than in the non-CVD group. Stroke is an independent risk factor for all-cause mortality in dialysis patients with CVD. These findings warrant further studies into preventive and interventional strategies.