Treatment options for colorectal cancer (CRC), especially in advanced stages are still insufficient. There, the discovery of Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was a bright spot. However, most cancers show resistance toward apoptotic signals. Cyclin-dependent kinase 9 (CDK9) plays a crucial role in cell cycle progression in most tissues. We recently demonstrated the role of CDK9 in mediating TRAIL resistance. In this work, we investigated the role of CDK9 in colorectal cancer. Immunohistochemical analysis of CDK9 expression in cancer and normal tissues of CRC specimens was performed. The effect of selective CDK9 inhibition in combination with TRAIL on CRC cells was analyzed via cell viability, colony formation, and induction of apoptosis by flow cytometry. The mechanism of action was conducted via western blotting. We now have confirmed overexpression of CDK9 in cancer tissues, with low expression associated with poorer survival in a subset of CRC patients. In-vitro, CDK9 inhibition could strongly promote TRAIL-induced cell death in TRAIL-resistant CRC cells. Mechanistically, CDK9 inhibition induced apoptosis by downregulation of antiapoptotic proteins, myeloid leukemia cell differentiation protein 1 (Mcl-1) and FLICE-inhibitory protein (c-FLIP). Overall, we identified CDK9 as a prognostic marker and combined CDK9 inhibition and TRAIL as a novel and promising therapeutic approaches for colorectal cancer.

Background: The relationship between gut microbiota and red blood cell folate levels in preeclampsia remains unclear. This study aimed to assess the differences in red blood cell folate levels and gut microbiota between pregnant women diagnosed with preeclampsia and healthy pregnant women and to investigate the association between gut microbiota composition and red blood cell folate concentrations. Methods: We employed a case-control study to investigate gut microbiota composition and red blood cell folate levels in preeclampsia, as well as the correlation between them. 10 pregnant women diagnosed with preeclampsia and 16 healthy pregnant women were recruited, and whole blood and stool samples were collected from all participants. For the blood samples, levels of total folate, 5-methyltetrahydrofolate, 5,10-methylenetetrahydrofolate, erythrocyte unmetabolized folate, and 5-formyltetrahydrofolate in red blood cells were measured utilizing high-performance liquid chromatography coupled with tandem mass spectrometry in Multiple Reaction Monitoring (MRM) mode. Microbial diversity in fecal samples was analyzed by 16S rRNA sequencing. The correlation between the microbiota α-diversity and red blood cell folate levels was calculated through Pearson correlation analysis. Results: There were no statistically significant differences in age, gestational age at the time of specimen collection, or body mass index between the preeclampsia group and the control group (all p > 0.05). Compared to the control group, the preeclampsia group showed significantly lower levels of total folate in red blood cells (p < 0.001), 5-methyltetrahydrofolate (p = 0.001), and 5,10-methylenetetrahydrofolate (p = 0.002). However, there were no differences in the levels of 5-acyltetrahydrofolate (p = 0.816) and unmetabolized folate (p = 0.241) in red blood cells between the two groups. Statistical analysis revealed significant differences between the two groups in several α-diversity indices of the gut microbiota, including the abundance-based coverage estimator (ACE) index (p = 0.011), Chao1 index (p = 0.010), PD_whole_tree index (p = 0.046), Shannon index (p = 0.015), and Simpson index (p = 0.043). These findings highlight notable differences in microbial diversity between the groups. The β-diversity analysis demonstrated significant compositional differences in the gut microbiota between samples, which were evident across multiple taxonomic ranks, including phyla, classes, orders, families, genera, and species. The Pearson correlation analysis revealed that levels of total folate, 5-methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate in red blood cells were significantly associated with the α-diversity of gut microbiota. Conclusions: Significant changes in erythrocyte folate level and intestinal microbiota diversity were observed in preeclampsia patients. Based on the limited data, the results of the Pearson correlation analysis indicate a significant association between red blood cell folate levels and gut microbiota diversity. However, this association should be interpreted with caution.

Background Pre-eclampsia (PE) is one of the serious complications of pregnancy, and the management of PE remains an important problem for obstetricians. This study aims to identify the characteristics and trends of published articles on PE management through bibliometric analysis. Methods We searched Web of Science database for articles related to PE management from 2000 to 2022. Metadata was obtained, including the titles, publication dates, authors, institutions, countries, and keywords of all articles, and then network visualization and burst keyword analysis were performed using Citespace and VOSviewer software. Results A total of 5190 articles were included in the analysis. The number of publications in the field of PE management has steadily increased over the years, and a visual analysis of collaborative networks of authors, institutions, and countries revealed that the United States, United Kingdom, Australia, and Canada have contributed the most to the field and formed extensive collaborations. The Journal of maternal-fetal & neonatal medicine has the most publications in this field, and the Journal of Obstetrics and gynecology has not only more publications but also 64.75 citations per article. The keywords mainly focused on prevention, diagnosis, risk factors, and outcome of PE. In addition, hypertensive disorders of pregnancy and fetal growth restriction have received a lot of attention in this field in recent years. Conclusions We analyzed the partnerships in PE management through bibliometrics and showed trends in the field. The available results suggest that PE management will continue to be a focus of attention.