Extracellular vesicles from Lacticaseibacillus paracasei PC-H1 inhibit HIF-1α-mediated glycolysis of colon cancer.

Aims: Extracellular vesicles from Lacticaseibacillus paracasei PC-H1 have antiproliferative activity of colon cells, but the effect on glycolytic metabolism of cancer cell remains enigmatic. The authors investigated how Lacticaseibacillus paracasei extracellular vesicles (LpEVs) inhibit the growth of colon cancer cells by affecting tumor metabolism. Materials & methods: HCT116 cells were treated with LpEVs and then differentially expressed genes were analyzed by transcriptome sequencing, the sequencing results were confirmed in vivo and in vitro. Results: LpEVs entered colon cancer cells and inhibited their growth. Transcriptome sequencing revealed differentially expressed genes were related to glycolysis. Lactate production, glucose uptake and lactate dehydrogenase activity were significantly reduced after treatment. LpEVs also reduced HIF-1α, GLUT1 and LDHA expression. Conclusion: LpEVs exert their antiproliferative activity of colon cancer cells by decreasing HIF-1α-mediated glycolysis.

Investigation of the inhibitory effect and mechanism of epigallocatechin-3-gallate against Streptococcus suis sortase A.

AIMS: Streptococcus suis seriously harms people and animals, and importantly, causes great economic losses in the pig industry. Similar to most Gram-positive pathogenic bacteria, sortase A (SrtA) of S. suis can mediate the anchoring of a variety of virulence factors that contain specific sorting sequences to the surface of the bacterial cell wall envelope and participate in pathogenicity. The purpose of this study is to clarify the molecular mechanism of epigallocatechin-3-gallate (EGCG) inhibiting S. suis SrtA and provide more evidence for the development of novel anti-S. suis infections drugs. METHODS AND RESULTS: Through the SrtA substrate cleavage experiment, we found that the main component of green tea, EGCG, can effectively inhibit the enzyme activity of S. suis SrtA. Further, molecular docking and molecular dynamics simulation were used to clarify the molecular mechanism of its inhibitory effect, demonstrating that EGCG mainly interacts with amino acids at 113 and 115 to exert its inhibitory function. It was previously found that EGCG can inhibit the growth of S. suis and reduce the activity of suilysin and inhibit its expression. Our research reveals a new function of EGCG in S. suis infection. CONCLUSIONS: Our research proves that EGCG can effectively inhibit the transpeptidase activity of SrtA. We also clarify the accompanying molecular mechanism, providing more sufficient evidence for the use of EGCG as a potential lead compound against S. suis infection.

Extracellular vesicles of Lacticaseibacillus paracasei PC-H1 induce colorectal cancer cells apoptosis via PDK1/AKT/Bcl-2 signaling pathway.

Colorectal cancer (CRC) is the third most common malignant tumor in the world. Previous research has shown that Lacticaseibacillus paracasei strains and its cultures have anti-colon cancer effects, but the study of L. paracasei-derived extracellular vesicles (LpEVs) as intercellular communication molecule against colon cancer has not been previously reported. Our research showed LpEVs were taken in by colorectal cancer cells. Subsequently, LpEVs inhibited the proliferation, migration, invasion and promote apoptosis of colorectal cancer cells. LpEVs inhibited the growth of CRC xenograft in nude mice and promoted tumor apoptosis in vivo. Transcriptome sequencing analysis revealed that differentially expressed genes were involved in the regulation of apoptosis. LpEVs significantly inhibited the phosphorylation level of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT in colorectal cancer cells and reduced the expression of Bcl-2 protein. In conclusion, extracellular vesicles of Lacticaseibacillus paracasei PC-H1 can inhibit the growth of colorectal cancer cells in vivo and vitro and induce apoptosis through PDK1/AKT/Bcl-2 signaling pathway. This research not only provides a new mechanism for the anti-tumor effects of probiotics, but also opens up new opportunity for the treatment of colon cancer.