Analysis of Function Role and Long Noncoding RNA Expression in Chronic Heart Failure Rats Treated with Hui Yang Jiu Ji Decoction.

Hui Yang Jiu Ji (HYJJ) decoction has been applied as a prescription of traditional Chinese medicine for the treatment of chronic heart failure (CHF). However, its comprehensive molecular mechanism remains unclear now. Our study aimed to explore the possible function and lncRNA-miRNA regulation networks of HYJJ on CHF induced by doxorubicin (DOX) in rats. Our study showed that HYJJ could recover cardiac function and alleviate myocardial injury of DOX-induced CHF. Besides, HYJJ had an effect on restraining myocardial apoptosis in CHF rats. Moreover, RNA-sequencing and bioinformatics analysis indicated that among a total of 548 significantly up- and down-regulated differentially expressed (DE) long noncoding RNA (lncRNA), 511 up- and down-regulated DE miRNAs were identified. Cushing's syndrome and Adrenergic signaling in cardiomyocytes were common pathways between DE-lncRNAs-enriched pathways and DE-miRNAs-enriched pathways. Finally, we observed a new pathway-MSTRG.598.1/Lilrb2 pathway with the HYJJ treatment; however, it needs further studies. In conclusion, this study provided evidence that HYJJ may be a suitable medicine for treating CHF. Moreover, several pivotal miRNAs may serve important roles in these processes by regulating some key miRNAs or pathways in CHF.

Effects of Salidroside Combined with Paclitaxel on Proliferation, Migration, and Epithelial Mesenchyme of Colorectal Cancer Cells.

Background: Colorectal cancer (CRC) is a multifactorial disease and one of the most common malignancies worldwide. Salidroside (Sal) is a plant with a wide range of pharmacological effects and plays an important role in the treatment of many diseases, and is considered a new hope for the treatment of tumors. The purpose of this study was to investigate the effect of the combination of Sal and paclitaxel (Pac) on colorectal cancer cells and its mechanism of action. Methods: The effects of different mass concentrations of Sal, Pac, and the combination intervened in the cells for 48 h were examined using the CCK8 method. The inhibition rate was obtained, and the optimal concentration of the respective drug group was screened. The proliferative capacity of the respective group was obtained. Subsequently, the results of apoptosis, cloning, migration, invasion, and angiogenesis were observed through cell morphological analysis (shape observation and Hoechst staining), colony formation assay, cell scratching assay, Transwell, angiogenesis assay, and protein immunoblotting (Western blotting) to detect the expression of epithelial-mesenchymal transition (EMT)-associated proteins and PI3K pathway-associated proteins. Results: Different concentrations of Sal, Pac, and the combined application had significant effects in inhibiting cells in a concentration-dependent manner. Compared with the control group, the Sal group, the Pac group, and the combination group significantly inhibited the clonal number, migration, invasion, and tube-forming ability of colorectal cancer cells. Besides, the combined application had a better effect than the Sal and Pac groups. The apoptosis level was up-regulated in all drug groups, and the up-regulation was more significant in the combination group. The expression of E-cad protein was up-regulated, the expression of N-cad and Vim protein was down-regulated, and the expression of PI3K and AKT phosphorylation was down-regulated in the respective group, and the difference was more significant in the combination group compared with the group of individual drugs. Conclusion: The combined application of Sal and Pac significantly can decrease the survival rate of colorectal cancer cells, and the mechanism may be correlated with the blocking of the PI3K/AKT pathway, thus inhibiting EMT.

Non-classical phenotypes of mismatch repair deficiency and microsatellite instability in primary and metastatic tumors at different sites in Lynch syndrome.

Background: Lynch syndrome is a genetic disease characterized by abnormal DNA replication caused by germline variation in the mismatch repair (MMR) gene. There are rare non-classical phenotypes with loss of MMR protein expression and inconsistent microsatellite stability (MSS) in Lynch syndrome-related colorectal cancers. However, the difference between microsatellite instability (MSI) of extraintestinal tumors in a patient with Lynch syndrome has been closely studied. Herein, we reported the non-classical phenotypes of mismatch repair deficiency (dMMR) and MSI in four cases of Lynch syndrome in patients with colorectal cancer and other primary and metastatic tumors. Methods: A retrospective analysis was conducted on four patients diagnosed with Lynch syndrome between 2018 and 2022 in the Department of Pathology of the Rocket Forces Specialized Medical Center. A one-step immunohistochemical (IHC) assay was employed to detect loss in the expression of Lynch syndrome-associated MMR proteins (MLH1, PMS2, MSH2, and MSH6). MSI detection was performed in both primary and metastatic tumors at different sites in the four patients using NCI 2B3D (BAT25, BAT26, D2S123, D17S250, and D5S346) and single nucleotide site (BAT25, BAT26, NR21, NR24, NR27, and MONO27) methods. In addition, related MMR gene germline variation, somatic mutations, and MLH1 gene promoter methylation were analyzed using next-generation sequencing and TaqMan probe-based methylation-specific polymerase chain reaction (MethyLight). Results: Two of the four patients were heterozygous for MSH6 germline pathogenic variation, and the other two were heterozygous for MSH2 germline pathogenic variation. In all cases, IHC detection of protein expression of the MMR gene with germline variation was negative in all primary and metastatic tumors; non-classical phenotypes of dMMR and MSI were present between primary and metastatic tumors at different sites. dMMR in Lynch colorectal cancer demonstrated high MSI, whereas MSI in primary and metastatic tumors outside the intestine mostly exhibited MSS or low MSI. Conclusions: The non-classical dMMR and MSI phenotype are mostly observed in Lynch syndrome, even in the context of MMR protein expression loss. Extraintestinal tumors infrequently present with a high degree of MSI and often exhibit a stable or low degree of MSI.