Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities in vitro and in vivo. This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK–OCMC Nps), which enhance the aqueous solubility and stability of GK. The GK–OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK–OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK–OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK–OCMC Nps. The GK–OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. In vitro drug release from GK–OCMC NPs was pH dependent. Moreover, the in vitro cytotoxicity study and cellular uptake assays indicated that the GK–OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK–OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9. GK–OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

In this study, we aim at investigating the expression and regulation role of long non-coding RNA (lncRNA) DLX6-AS1 in bladder cancer (BC). DLX6-AS1 was highly expressed in BC tissues and significant negative correlation with the 5-year survival in the BC patients. The results showed that the proliferation, migration and invasion activities of BC cells were promoted by DLX6-AS1 overexpression, while cell apoptosis was repressed. However, knockdown DLX6-AS1 presented an pposite regulatory effect, and DLX6-AS1 knockdown delayed tumor in vivo. The potential target of DLX6-AS1 in BC was predicted and verified by RIP, RNA pull-down, and dual-luciferase reporter assays as miR-195-5p. The results showed that miR-195-5p was down-regulated in BC tissues, the expression of which was significantly negative correlated with DLX6-AS1 expression. In addition, the results also showed that miR-195-5p targeted and down-regulated the VEGFA. Knockdown of DLX6-AS1 up-regulated miR-195-5p expression and down-regulated VEGFA expression. Moreover, down-regulation of VEGFA expression caused by DLX6-AS1 inhibited phosphorylation of Raf-1, MEK1/2, and ERK1/2, while miR-195-5p inhibitors abolished the effect of silencing DLX6-AS1 expression. Our study demonstrated that DLX6-AS1 played an oncogenic role in BC through miR-195-5p-mediated VEGFA/Ras/Raf/MEK/ERK pathway.

20(S)-ginsenoside Rh2 (Rh2), a well-known protopanaxadiol-type ginsenoside from Panax ginseng has especially gained attention for its anticancer activities on various types of human cancer cells. However, the molecular mechanism through which Rh2 promotes apoptosis in hepatocellular carcinoma (HePG2) cells is not known at the transcriptome level. Rh2 can specifically inhibit the proliferation of HePG2 in a dose- and time-dependent manner. Moreover, Rh2 can significantly increase the apoptosis which was related with an increase in protein expression levels of caspase-3, caspase-6, and poly (ADP-ribose) polymerase. Comparison of RNA-seq transcriptome profiles from control group and Rh2-treated group yielded a list of 2116 genes whose expression was significantly affected, which includes 971 up-regulated genes and 1145 down-regulated genes. The differentially expressed genes in p53 signaling pathway and DNA replication may have closely relationships to the cells apoptosis caused by Rh2 treatment. The results of qPCR validation showed that dynamic changes in mRNA, such as CDKN1A, CCND2, PMAIP1, GTSE1, and TP73.

Erectile Dysfunction (ED) is considered a physical and mental illness. A variety of potential associations between gut microbiota and health or disease have been found. By comparing the gut microbiota of healthy controls and ED patients, our study investigated the relationship between ED and gut microbiota. The results revealed that the ED group exhibited a significantly higher relative abundance of Bacteroides , Fusobacterium , Lachnoclostridium , Escherichia‐Shigella and Megamonas , while showing a significantly lower relative abundance of Bifidobacterium compared to the control group. The dysbiosis of gut microbiota played a role in the onset and progression of ED by influencing the gut barrier, cardiovascular system and mental health, which provided a novel perspective on understanding the pathophysiology of ED. What is more, we had identified several key gut microbiota. By combining 16S rRNA sequencing with machine learning techniques, we were able to uncover the significant value and impact of gut microbiota in the early detection of ED.

Background: Mounting evidence has demonstrated that circular RNAs (circRNAs) play indispensable roles in the progression of bladder cancer. Public database mining showed that hsa_circRNA_100146 (circRNA_100146) was highly expressed in bladder cancer. This study aimed to characterize the biological role of circRNA_100146 and clarify the underlying mechanism in bladder cancer. Methods: We evaluated the relationship between circRNA_100146 expression and clinicopathological features. Furthermore, gain- and loss-of-function studies were conducted in bladder cancer cells via transfection with gene-carrying plasmids (over-expression) or specific short hairpin RNAs (knockdown). Moreover, computational algorithms and dual-luciferase reporter assays were performed to explore the possible mechanisms of action. Additionally, in vivo xenograft experiments were performed to further analyze the effect of circRNA_100146 on tumor growth. Results: Our data showed that circRNA_100146 expression was increased in bladder cancer tissues and cell lines, and that high expression of circRNA_100146 was correlated with poor patient prognosis. Upregulation of circRNA_100146 promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, whereas knockdown of circRNA_100146 displayed opposite effects on bladder cancer cells. Notably, circRNA_100146 could combine with miR-149-5p and promote ring finger protein 2 (RNF2) expression, thereby facilitating the progression of bladder cancer. Furthermore, overexpression of RNF2 reversed the effects of circRNA_100146 knockdown on the biological behaviors of bladder cancer cells. The in vivo experiments revealed that downregulation of circRNA_100146 dramatically delayed tumor growth. Conclusion: Our findings indicate that circRNA_100146 functions as a sponge of miR-149-5p in promoting bladder cancer progression by regulating RNF2 expression and that circRNA_100146 may serve as a novel biomarker in human bladder cancer.