Open Medicine最新文献

Objectives: This narrative review aims to update the current evidence and offer insight into the new non-invasive ultrasound techniques used to early identify degenerative vascular changes in subjects with periodontitis and to investigate if these methodologies could be useful to identify subclinical cardiovascular disease (CVD) dysfunction in periodontitis patients and to monitor changes in CVD risk after periodontal treatment.

Methods: Studies examining the assessment of vascular endothelial function through the latest methodologies were analyzed. Systematic reviews, observational studies, and clinical trials in the English language were identified using PubMed, Web of Science, and Google Scholar databases with key search terms such as "periodontitis," "endothelial dysfunction (ED)," "arterial stiffness," and "periodontal therapy."

Results: Several mechanisms are involved in the association between periodontitis and CVD. The key players are periodontal bacteria and their toxins, which can enter the circulation and infiltrate blood vessel walls. The increase in proinflammatory molecules such as interleukins and chemokines, c-reactive protein, fibrinogen, and oxidative stress also plays a decisive role. In addition, an increase in parameters of ED, arterial stiffness, and atherosclerosis, such as carotid intima-media thickness, pulse wave velocity, and flow-mediated dilatation, has been shown in periodontal patients.

Conclusions: The literature today agrees on the association of periodontitis and CVD and the positive role of periodontal therapy on systemic inflammatory indices and cardiovascular outcomes. Hopefully, these non-invasive methodologies could be extended to periodontal patients to provide a comprehensive understanding of the CVD-periodontitis link from the perspective of a personalized medicine approach in periodontology.

Background: No intervention definitively extends transplant-free survival in primary sclerosing cholangitis (PSC). Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), may enhance PSC prognosis, but their efficacy is debated.

Methods: We analyzed HMGCR single-nucleotide polymorphisms from published genome-wide association studies using Mendelian randomization to assess the causal relationship between HMGCR and PSC risk. Effects of HMGCR were compared with proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, common lipid-lowering drugs, using coronary heart disease risk as a positive control. The inverse-variance weighted (IVW) method was the primary analysis, complemented by the weighted median method. Heterogeneity analysis, examination of horizontal pleiotropy, and leave-one-out sensitivity analysis were conducted for result robustness.

Results: Genetically predicted HMGCR exhibited a pronounced detrimental effect on PSC in both the IVW method (odds ratio [OR] [95%] = 2.43 [1.23-4.78], P = 0.010) and the weighted median method (OR [95%] = 2.36 [1.02-5.45], P = 0.044). However, PCSK9 did not reach statistical significance. Moreover, all analyses passed through heterogeneity analysis, horizontal pleiotropy analysis, and leave-one-out sensitivity analysis.

Conclusion: This study has confirmed a causal relationship between HMGCR and PSC risk, suggesting statins targeting HMGCR could enhance PSC patient outcomes.

Backgrounds: The integrator complex (INT) is a multiprotein assembly in gene transcription. Although several subunits of INT complex have been implicated in multiple cancers, the complex's role in gastric cancer (GC) is poorly understood.

Methods: The gene expressions, prognostic values, and the associations with microsatellite instability (MSI) of INT subunits were confirmed by GEO and The Cancer Genome Atlas (TCGA) databases. cBioPortal, GeneMANIA, TISIDB, and MCPcounter algorithm were adopted to investigate the mutation frequency, protein-protein interaction network, and the association with immune cells of INT subunits in GC. Additionally, in vitro experiments were performed to confirm the role of INTS11 in pathogenesis of GC.

Results: The mRNA expression levels of INTS2/4/5/7/8/9/10/11/12/13/14 were significantly elevated both in GSE183904 and TCGA datasets. Through functional enrichment analysis, the functions of INT subunits were mainly associated with snRNA processing, INT, and DNA-directed 5'-3' RNA polymerase activity. Moreover, these INT subunit expressions were associated with tumor-infiltrating lymphocytes and MSI in GC. In vitro experiments demonstrated that knockdown of the catalytic core INTS11 in GC cells inhibits cell proliferation ability. INTS11 overexpression showed opposite effects.

Conclusions: Our data demonstrate that the INT complex might act as an oncogene and can be used as a prognosis biomarker for GC.