Journal of Translational Internal Medicine最新文献

Background and objectives: Prior studies have highlighted an escalating global burden of hepatocellular carcinoma (HCC). The Notch signaling pathway regulates the initiation and development of HCC and determines the HCC prognosis.

Methods: The expression data of genes related to the Notch signaling pathway were acquired from public databases. To filter prognostic gene signatures and establish the risk model, the analyses of consensus clustering, least absolute shrinkage and selection operator (LASSO), and multivariate Cox were conducted. Subsequently, the risk stratification was optimized using a decision tree and nomogram. The immune landscapes were revealed utilizing the single-sample gene set enrichment analysis, and tumor immune dysfunction and exclusion score.

Results: According to the mRNA expression profile of Notch signaling pathway-related genes, HCC patients were stratified to three clusters, which have different survival probability and immune infiltration characteristic. Subsequently, we developed a risk model based on five prognostic Notch signaling-related gene signatures (SPP1, SMG5, HMMR, PLOD2, and CFHR4). The model demonstrated an accurate estimation of overall survival, revealing alterations in immune status and immunotherapy sensitivity among HCC patients with different risk scores.

Conclusions: This study constructed a Notch signaling pathway-related prognostic model, offering valuable insights for the assessment of immune characteristics and immunotherapy responses in HCC patients.

Background and objectives: Cholangiocarcinoma (CHOL) is a rare and highly aggressive cancer that originates in the bile duct; it has an average five-year survival rate of 9%, which makes it the cancer with the lowest survival rate among all 33 cancer types in the cancer genome atlas (TCGA) Program. The aim of this study is to elucidate the key determinants of the high malignancy level of CHOL through computational and cell-based experimental approaches and, particularly, to investigate how bile acids (BAs) influence CHOL's propensity to metastasize.

Methods: Our study analyzed the transcriptomic data from 1835 tissue samples of 7 digestive system cancer types in the TCGA database and compared them with those of 330 control tissue samples. Multiple cellular and molecular factors were considered in the study, including the level of hypoxia, level of immune cell infiltration, degree of cellular dedifferentiation, and level of sialic acid (SA) accumulation on the surface of cancer cells. Using these factors, we developed a multivariable regression model for the five-year survival rate, as reported by the Surveillance, Epidemiology, and End Results (SEER) Program reports, and analyzed how BA biology influences a few of these factors and causes CHOL to have a high malignancy level.

Results: CHOL exhibited the highest level of SA accumulation and B-cell infiltration among all cancer types studied. BAs inhibit the cell cycle progression through the receptor GPBAR1, thereby limiting the rate of nucleotide biosynthesis-which in turn forces the cells to increase SA biosynthesis in order to maintain the intracellular pH at a stable level-thereby driving cell migration and metastasis, as established in our previous study.

Conclusions: BAs are the key contributors to the lowest five-year survival rate of CHOL among the seven cancer types studied here. This finding not only reveals the molecular mechanisms underlying the high malignancy level of CHOL but also provides a new potential target for the diagnosis and treatment of CHOL.

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.