Journal of Translational Internal Medicine最新文献

Polycystic kidney disease (PKD) is a genetic disorder marked by numerous cysts in the kidneys, progressively impairing renal function. It is classified into autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD), with ADPKD being more common. Current treatments mainly focus on symptom relief and slowing disease progression, without offering a cure. Recent advancements in gene editing technologies, such as CRISPR-Cas9, have introduced new therapeutic possibilities for PKD. These approaches include miR-17 antisense oligonucleotides, adenovirus-mediated gene knockdown, Pkd1 gene or polycystin -1 C-terminal tail enhancement therapy, and 3-UTR miR-17 binding element by CRISPR-Cas9, which have shown potential in animal models and early clinical trials. Specifically for ARPKD, strategies like antisense oligonucleotide therapy targeting c-myc and CRISPR/ Cas9 knockdown of the P2rx7 gene have shown promise. Despite facing challenges such as technological limitations, ethical and legal issues, and high costs, gene therapy presents unprecedented hope for PKD treatment. Future interdisciplinary collaboration and international cooperation are essential for developing more effective treatment strategies for PKD patients.

Background and objectives: The association between chronic kidney disease (CKD) and cardiovascular disease has been previously evaluated. This study aimed to evaluate the association between the American Heart Association's Life's Essential 8 (LE8) and the prevalence and all-cause mortality of CKD in a nationally representative population of adults in the US.

Methods: This retrospective analysis included participants from the National Health and Nutrition Examination Survey spanning 2015-2018. We used multivariable survey logistic regression model to calculate the adjusted odds ratios (AORs) of the LE8 score for the prevalence of CKD. Survey-weighted Cox proportional hazards models were used to calculate the adjusted hazards ratios (AHRs) of the LE8 score for the risk of all-cause mortality among participants with CKD.

Results: Of the 8907 included participants, 789 had stage 3 to 5 CKD, and 8118 were in the non-CKD group. The adjusted prevalence rate of CKD was 10.7% in the low LE8 score group, and lower in the moderate (7.9%) and high (7.7%) LE8 score groups. Compared with low LE8 scores, moderate LE8 score (adjusted odds ratio [AOR] 0.628, 95% confidence interval [CI]: 0.463 to 0.853, P = 0.004) and high LE8 scores (AOR 0.328, 95% CI: 0.142 to 0.759, P = 0.011) were associated with lower prevalence rates of CKD. A similar association was found for health factors scores. Additionally, an increase in the LE8 score was associated with a lower risk of all-cause mortality (adjusted hazard ratio [AHR] 0.702, 95% CI: 0.594 to 0.829, P < 0.001).

Conclusion: The results of this study suggest the association of higher LE8 and its subscale scores with a lower prevalence and all-cause mortality of CKD.

Background and objectives: Histone deacetylase (HDAC) families regulate various physical processes and the development of several diseases. The role of HDACs in asthma development and progression worths further investigation. This study aims to evaluate the effect of HDACs in a mouse model of asthma.

Methods: HDAC8 selective inhibitor PCI-34051 was administered to a mouse model of ovalbumin-sensitized and challenged asthma. Airway responsiveness, serum cytokines, histological changes of the airway, and expression levels of α-SMA, β-actin, VEGFR, VEGF, GAPDH, HDAC8, TGF-β3, CD 105, p-ERK 1/2, ERK 1/2, PI3K, p-AKT, AKT, and PDK1 were evaluated. The miR-381-3p level was also measured.

Results: All classic histologic and cellular changes of asthma in inflammation and airway remodeling were altered by HDAC8 inhibitor PCI-34051 via regulation of the miR-381-3p level and its downstream gene, TGF-β3. Inhibition of TGF-β3 further reduced the activation of ERK, PI3K, AKT, and PDK1.

Conclusion: In a mouse model, HDAC8 inhibitor PCI-34051 exhibits comprehensive control of asthmatic changes, including inflammation and airway remodeling.

Background and objective: Atrial fibrillation (AF) and coronary heart disease (CHD) are closely related to metabolic dysregulation. However, the metabolic characteristics of AF patients with concomitant CHD remain unclear. The aims of this study were to elucidate the metabolic profiles of patients with AF and CHD to seek new therapeutic targets and related factors of AF combined with CHD.

Methods: Untargeted metabolomics and targeted oxylipins profiling were performed to characterize the serum metabolome landscape of patients with AF, CHD, and AF comorbid CHD.

Results: The serum metabolic fingerprints of patients with AF comorbid CHD were significantly differentiated from normal controls (NC) and individuals with AF or CHD alone, and the differentiated metabolites dominated by a variety of lipid alterations in the phospholipid and fatty acid metabolism. Furthermore, the targeted profiles of oxylipins demonstrated that the levels of arachidonic acid derivatives including prostaglandins, leukotrienes, hydroxy-docosahexaenoic acids, hydroxy-eicostetraenoic acids and hydroxy-eicosatrienoic acids in patients with AF and CHD were significantly different from those in the NC, AF, and CHD groups. Several prostaglandins were positively associated with echocardiographic indicators of myocardial remodeling.

Conclusions: This study updates metabolic insights of AF and CHD and provides potential therapeutic targets for preventing or treating AF comorbid CHD.