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PPARα (peroxisome-proliferator-activated receptor α) plays a critical role in regulation of inflammation and cancer, while the regulatory mechanism of PPARα on cancer cell autophagy is still unclear. Here we found that PPARα enhanced autophagy in HEK293T, SW480, and Hela cell lines, which was independent of PPARα transcription activity. PPARα induced antiapoptotic Bcl2 protein degradation resulting in release of the Beclin-1/VPS34 complex. Consistently, silenced PPARα reversed this event. PPARα-induced autophagy significantly inhibited tumor growth and enhanced SW480 cancer cell sensitivity to chemotherapy drugs. Moreover, PPARα agonist increased SW480 cancer cell chemotherapy sensitivity. These findings revealed a novel mechanism of PPARα/Bcl2/autophagy pathway suppressed tumor progression and enhanced chemotherapy sensitivity, which is a potential drug target for cancer treatment.

Licorice, the root of Glycyrrhiza glabra L. (Leguminosae), is one of the oldest known medicinal herbs. Glycyrrhizic acid (GA), a triterpenoid saponin isolated from licorice, has a variety of pharmacological activities. Previous studies indicate that GA produces neuroprotection via the modulation of anti-apoptotic and pro-apoptotic factors, primarily through the ERK signaling pathway and the suppression of inflammatory cytokine induction. However, the mechanisms of these neuroprotective effects and the effects of neuroimmunomodulation on cognition are not fully elucidated. This study investigated the effects of GA in preventing age-related immune involution and cognitive disorders as well as the relationship between immune involution and cognition and the underlying molecular mechanisms. Twelve-month-old female C57BL/6 mice were injected with GA (5mg/kg i.v. once every other day) for 6 weeks. Then, we tested the behavioral effects of GA using the Morris water maze task to evaluate spatial learning and memory. Age-related learning and memory impairments were prevented by GA treatment. This effect was accompanied by improved cerebral blood flow. Transcriptome analysis of C57BL/6 mice blood by RNA-sequencing and KEGG pathway analysis showed that GA could significantly influence hematopoietic cell lineage. The differential genes in the pathway were clustered using heat mapping, and RNA-seq results showed that GA altered gene expression. To correlate modulated gene expression and cognitive effects, we analyzed the levels of CD3e+ positive T cells, CD45R/B220+ positive B cells, and CD49b+ positive NK cells in the blood and spleen after 22 days of GA treatment. Flow cytometry showed that GA could increase T and B cells in the blood and spleen. To further investigate the relationship between neuroprotective effects of GA and effects on T and B cells, we tested behaviors after immunological reconstitution and GA treatment using a novel object recognition task in B-NDG mice. We found that, following immunological reconstitution and GA treatment, mice showed an increased preference for novel objects compared with controls as well as increased numbers of T, B, CD4, and CD8 cells. Increased neural stem cell markers accompanied these changes. Thus, our study suggests that GA may be a potential treatment for alleviating aging-associated cognitive declines and that these effects may be related to immune system modulation.

To evaluate the micro-ecological effects of tetracycline residues on tobacco soil, high-throughput sequencing technology was used to study the effects of the addition of different concentrations (0, 5, 50, and 500 mg·kg−1) of tetracycline on the abundance, diversity, and structure of bacterial and fungal communities in the rhizosphere and non-rhizosphere soil of flue-cured tobacco in China. Results showed that the presence of tetracycline had an important but varying effect on soil bacterial and fungal community richness, diversity, and structure. Changes in the diversity indices (Chao index and Shannon index) of soil bacterial and fungal communities showed a similar pattern after the addition of tetracycline; however, a few differences were found in the effects of tetracycline in the rhizosphere and non-rhizosphere soil, suggesting an evident rhizosphere-specific effect. The bacterial community at the phylum level in the rhizosphere closely clustered into one group, which might be the result of tobacco root secretions and rhizodeposition. Tetracycline showed a concentration-dependent effect on the soil bacterial community structure. The soil bacterial community structures observed after treatments with higher concentrations of tetracycline (50 and 500 mg·kg−1) were found to be closely related. Moreover, the effects of the treatments with higher concentrations of tetracycline, on the soil bacterial community at the phylum level, were different from those with lower concentrations of tetracycline (5 mg·kg−1), and CK treatments. This might have resulted from the induction of increasing selective pressure with increasing antibiotic concentration. Tetracycline continued to affect the soil bacterial community throughout the experiment. Tetracycline was found to have a varying impact on the community structure of soil fungi compared to that of soil bacteria, and the addition of an intermediate concentration of tetracycline (50 mg·kg−1) significantly increased the soil fungal diversity in the non-rhizosphere soil. The biological effects of tetracycline on the soil fungal community and the fungal-bacterial interactions, therefore, require further elucidation, warranting further research.

Dysregulated expression of epidermal growth factor receptor (EGFR) has been implicated in many cancer events, while peroxisome proliferator-activated receptor γ (PPARγ) negatively regulates cancer progression. The molecular mechanism of EGFR interaction with PPARγ is still unclear. Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase. PPARγ degradation by EGFR/MDM2 signaling resulted in accumulation of nuclear factor-kappaB (NF-κB)/p65 protein levels and increasing NF-κB activation. In contrast, PPARγ-Y74A mutant reversed this event. Moreover, PPARγ-Y74A mutant suppressed cell proliferation and increased chemotherapeutic agent-induced cancer cell sensitivity. Importantly, the clinical findings show that the nuclear phosphorylation of PPARγ-Y74 and EGFR expression in colonic cancer tissues was higher than that in control normal tissues. Thus, our study revealed a novel molecular mechanism that nuclear EGFR/NF-κB signaling promoted cell proliferation by destructing PPARγ function, which provides a novel strategy for cancer treatment.