ABSTRACT
Depression, as a common mental illness that is often accompanied by suicidal and homicidal behaviors, is one of the most important diseases in the medical field that requires urgent attention. The pathogenesis of depression is complex, and the current therapeutic drugs such as tricyclic antidepressants (TCAs), monoamine oxidase inhibitors, and secondary serotonin reuptake inhibitors have certain shortcomings. The inflammatory factor hypothesis, one of the pathogenesis of depression, suggests that inflammatory response is a key factor leading to the occurrence and development of depression, and that overactivation of inflammatory factors such as NLRP3, Toll-like receptor 4, and IDO leads to immune-system dysfunction and depression. The other pathogenic hypothesis, the gut flora hypothesis, has also been the focus of recent research. The gut flora may work together with inflammatory factors to cause depression. The approach to treating depression has been by altering the gut flora through drugs or probiotics. However, effective and clear treatment methods are lacking. In this study, by exploring the involvement of intestinal flora and inflammatory factors in the pathogenesis of depression, we found that improving the intestinal flora can affect inflammatory factors and, therefore, provide research ideas for the development of novel drugs to treat depression.
ABSTRACT
BACKGROUND: Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori (H. pylori) infections. Therefore, there is an urgent need to develop new antimicrobial agents to replace antibiotics. Our previous study found that linolenic acid-metronidazole (Lla-Met) has a good antibacterial effect against H. pylori, both antibiotic-resistant and sensitive H. pylori. Also, H. pylori does not develop resistance to Lla-Met. Therefore, it could be used for preparing broad-spectrum antibacterial agents. However, since the antibacterial mechanism of Lla-Met is not well understood, we explored this phenomenon in the present study. AIM: To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections. METHODS: H. pylori cells were treated with the Lla-Met compound, and the effect of the compound on the cell morphology, cell membrane permeability, and oxidation of the bacteria cell was assessed. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified. RESULTS: Lla-Met treatment induced several changes in H. pylori cells, including roughening and swelling. In vivo experiments revealed that Lla-Met induced oxidation, DNA fragmentation, and phosphatidylserine ectropionation in H. pylori cells. Inhibiting Lla-Met with L-cysteine abrogated the above phenomena. Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes, both anti-oxidation-related genes. CONCLUSION: Lla-Met kills H. pylori mainly by inducing oxidative stress, DNA damage, phosphatidylserine ectropionation, and changes on cell morphology.
