Background Oxidative stress and the resulting inflammation are essential pathological processes in acute lung injury (ALI). Nuclear factor erythroid 2-related factor 2 (Nrf2), a vital transcriptional factor, possesses antioxidative potential and has become a primary target to treat many diseases. Oridonin (Ori), isolated from the plant Rabdosia Rrubescens, is a natural substance that possesses antioxidative and anti-inflammatory effects. Our aim was to study whether the anti-inflammatory and antioxidant effects of Ori on LPS-induced ALI were mediated by Nrf2. Methods MTT assays, Western blotting analysis, a mouse model, and hematoxylin-eosin (H & E) staining were employed to explore the mechanisms by which Ori exerts a protective effect on LPS-induced lung injury in RAW264.7 cells and in a mouse model. Results Our results indicated that Ori increased the expression of Nrf2 and its downstream genes (HO-1, GCLM), which was mediated by the activation of Akt and MAPK. Additionally, Ori inhibited LPS-induced activation of the pro-inflammatory pathways NLRP3 inflammasome and NF-κB pathways. These two pathways were also proven to be Nrf2-independent by the use of a Nrf2 inhibitor. In keeping with these findings, Ori alleviated LPS-induced histopathological changes, the enhanced production of myeloperoxidase and malondialdehyde, and the depleted expression of GSH and superoxide dismutase in the lung tissue of mice. Furthermore, the expression of LPS-induced NLRP3 inflammasome and NF-κB pathways was more evident in Nrf2-deficient mice but could still be reversed by Ori. Conclusions Our results demonstrated that Ori exerted protective effects on LPS-induced ALI via Nrf2-independent anti-inflammatory and Nrf2-dependent antioxidative activities.

Lung carcinoma is the most common human cancer with poor prognosis and has an increasing incidence in recent years. However, the related mechanism of lung cancer onset has not been completely explored. Piwi-interacting RNA (piRNA) is a type of noncoding small RNA with established function in germ cells, and interestingly, piRNA has also been shown to be implicated in cancer biology. In this study, piR-55490 was found to be silenced in lung carcinoma specimens and cell lines, compared with normal lung tissues and cells. Intriguingly, the expression level of piR-55490 is negatively associated with patients' survival. Restoration of piR-55490 can reduce the proliferation rates of lung cancer cells, while piR-55490 suppression led to the gain in the proliferation rates. Animal model study showed that piR-55490 can suppress the growth of lung carcinoma xenograft. Further study revealed that piR-55490 suppressed the activation of Akt/mTOR pathway in lung cancer cells. Surprisingly, piR-55490 was found to bind 3'UTR of mTOR messenger RNA (mRNA) and induce its degradation in a mechanism similar to microRNA (miRNA). The introduction of an mTOR construct resistant to action of piR-55490 was able to abolish the effect of piR-55490 on lung cancer cells. In conclusions, we found that piRNA can contribute to the suppression of cancer cell phenotypes by directly targeting a oncogene mRNA. This finding facilitates our understanding of piRNA's function and its association with human cancer.

6′-O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from peony root, has been proven to possess antioxidant potential. In this present study, we revealed that GPF treatment exerted significant neuroprotection of PC12 cells following OGD, as evidenced by a reduction of oxidative stress, inflammatory response, cellular injury, and apoptosis in vitro. Furthermore, treatment with GPF increased the levels of phosphorylated Akt (p-Akt) and nuclear factor-erythroid 2-related factor 2 (Nrf2), as well as promoted Nrf2 translocation in PC12 cells, which could be inhibited by Ly294002, an inhibitor of phosphoinositide 3-kinase (PI3K). In addition, Nrf2 knockdown or Ly294002 treatment significantly attenuated the antioxidant, anti-inflammatory, and antiapoptotic activities of GPF in vitro. In vivo studies indicated that GPF treatment significantly reduced infarct volume and improved neurological deficits in rats subjected to CIRI, as well as decreased oxidative stress, inflammation, and apoptosis, which could be inhibited by administration of Ly294002. In conclusion, these results revealed that GPF possesses neuroprotective effects against oxidative stress, inflammation, and apoptosis after ischemia-reperfusion insult via activation of the PI3K/Akt/Nrf2 pathway.

This study aimed to investigate the levels of willingness to use pre-exposure prophylaxis (PrEP) and intention to adhere to PrEP and to further explore factors associated with PrEP uptake among men who have sex with men (MSM) in China. A total of 524 MSM were recruited from Chengdu, China. Half of the participants had heard of PrEP, and the awareness rate varied from 33.8%, 30.7%, and 7.1% for daily oral PrEP, on-demand PrEP, and long-acting injectable PrEP (LAI-PrEP), respectively. The overall willingness to use any type of PrEP in the next six months was 84.9% if PrEP is effective and provided for free. Participants were less likely to say that they would use PrEP if they used a condom consistently with their regular partners. However, participants were more likely to say that they would use PrEP if they had casual partners in the past month and had higher HIV prevention literacy. The majority of participants intended to adhere to PrEP prescription. More than forty percent (43.1%) of the participants reported that they might reduce condom use if they took PrEP. We found that the overall willingness to use PrEP was high among MSM living in China, but willingness varied across the different types of PrEP.

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