Tiliroside attenuates acute kidney injury by inhibiting ferroptosis through the disruption of NRF2-KEAP1 interaction.

BACKGROUND: Ferroptosis, an iron-dependent process that regulates cell death. Emerging evidences suggest that ferroptosis induces acute kidney injury (AKI) progression, and inhibiting ferroptosis provides an effect strategy for AKI treatment. The disruption of the NRF2-KEAP1 protein to protein interaction (PPI) induces NRF2 activation, which provides a promising strategy that can identify new ferroptosis inhibitors. A previous study revealed that tiliroside, a glycosidic flavonoid extracted from Edgeworthia chrysantha Lindl (buds), has anti-neuroinflammatory and neuroprotective effects via NRF2 activation. However, the mechanism through which tiliroside activates NRF2 is unknown, and it remains unclear whether it has protective effects against AKI. PURPOSE: To investigate whether tiliroside has protective effects against AKI in mice and the associated mechanisms. METHODS: Possible tiliroside substrates were analyzed using molecular docking. Cisplatin- and ischemia-reperfusion injury (IRI)-induced AKI mouse models and HK2 cells model were constructed to evaluate the protective effects of tiliroside. CRISPR/Cas9 mediated NRF2 knockout HK2 cells were used to verify whether NRF2 mediates tiliroside protective effects. RESULTS: In vivo, our results showed that tiliroside treatment preserved kidney functions in AKI mice models, as showed by lower levels of serum creatinine (SCr), blood urea nitrogen (BUN), and renal injury markers, including neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM1), compared with the mice in control groups. In vitro, tiliroside treatment greatly ameliorated cisplatin-induced ferroptosis through NRF2 activation in cultured HK2 cells, as evidenced by the protective effects of tiliroside being greatly blunted after the knockout of NRF2 in HK2 cells. Mechanistic studies indicated that tiliroside promoted NRF2/GPX4 pathway activation and ferroptosis inhibition, perhaps via the disruption of the NRF2-KEAP1 PPI. CONCLUSION: Together, our results demonstrate that tiliroside may serve as a NRF2-KEAP1 PPI inhibitor and prevents ferroptosis-induced AKI, indicating its potential for clinical AKI treatment.

Identification and functional analysis of a pollen fertility-associated gene GhGLP4 of Gossypium hirsutum L.

KEY MESSAGE: Cotton male fertility-associated gene GhGLP4, encoding a germin-like protein, is essential for anthers development by keeping ROS homeostasis through reducing H2O2 level. Utilization of heterosis is an important way to increase cotton yield and improve fiber quality in hybrid cotton development programs. Male sterility is used in the development of cotton hybrids to reduce the cost of hybrid seed production by eliminating the process of emasculation. From the transcriptome analysis of genic male sterile mutant (ms1) and its background C312 of G. hirsutum, a gene encoding germin-like protein (GhGLP4) was found significantly down-regulated in different developmental stages of ms1 anthers. To explore the gene function in cotton fertility, GhGLP4 was further studied and interfered by virus-induced gene silencing. In the GhGLP4 interfered cotton lines, the expression level of GhGLP4 was significantly decreased in the stamens, and the down-regulation of GhGLP4 resulted in pollen sac closure, stigma exertion, filament shortening, decrease in the number of anthers and complete male sterility. The expression levels of respiratory burst oxidase homologs (Rboh, NADPH oxidase) were significantly altered. Further investigation showed that the SOD activity decreased while the H2O2 content increased in the atypical stamens. These results indicated that GhGLP4 gene affected the cotton anther development through maintenance of ROS homeostasis by H2O2 reduction.

Traditional Chinese Medicine in Emergency Treatment Mechanism and Application.

Traditional Chinese medicine has usually been recognized to be efficacious to treat chronic diseases from the western point-of-view. However, there is a long history in China of applying traditional Chinese medicine in many acute and urgent medical conditions. In this review, selected methods documented in traditional Chinese medicine including blowing air to ear, nose insufflating therapy, acupuncture and moxibustion were presented as the common practices to promote consciousness recovery from coma. We aimed to explore the mechanism of these four methods with current scientific evidence, further discuss the potential of traditional Chinese medicine to be applied in emergency medicine and provide a path forward to more rigorously validate these procedures. The development of the integrated traditional Chinese medicine and western medicines provides a new therapeutic direction for the new first-aid treatment.

CSCD: a database for cancer-specific circular RNAs.

Circular RNA (circRNA) is a large group of RNA family extensively existed in cells and tissues. High-throughput sequencing provides a way to view circRNAs across different samples, especially in various diseases. However, there is still no comprehensive database for exploring the cancer-specific circRNAs. We collected 228 total RNA or polyA(-) RNA-seq samples from both cancer and normal cell lines, and identified 272 152 cancer-specific circRNAs. A total of 950 962 circRNAs were identified in normal samples only, and 170 909 circRNAs were identified in both tumor and normal samples, which could be further used as non-tumor background. We constructed a cancer-specific circRNA database (CSCD, http://gb.whu.edu.cn/CSCD). To understand the functional effects of circRNAs, we predicted the microRNA response element sites and RNA binding protein sites for each circRNA. We further predicted potential open reading frames to highlight translatable circRNAs. To understand the association between the linear splicing and the back-splicing, we also predicted the splicing events in linear transcripts of each circRNA. As the first comprehensive cancer-specific circRNA database, we believe CSCD could significantly contribute to the research for the function and regulation of cancer-associated circRNAs.

Variations of Growth and Toxin Yield in Cylindrospermopsis raciborskii under Different Phosphorus Concentrations.

The bloom-forming cyanobacteria, Cylindrospermopsis raciborskii, is a producer of the cytotoxic cylindrospermopsin (CYN). In this study, the growth, toxin yield, and expression of CYN biosynthesis genes of C. raciborskii were examined under varying phosphorus (P) concentrations. The results show the cell number at 0.00 and 0.01 mg·L-1 P was significantly lower than that at higher P concentrations (≥0.5 mg·L-1). The chlorophyll a content, filament length, heterocyst, and akinete numbers at P ≤ 0.05 mg·L-1 were also significantly reduced. The intracellular and extracellular CYN concentrations and the extracellular proportions increased during the culture period, and larger values were observed at higher P concentrations. Total CYN content reached 45.34-63.83 fg·cell-1 and extracellular CYN proportion reached 11.49%-20.44% at the stationary growth phase. A significantly positive correlation was observed between CYN production and cell growth rate. Three cyr genes were expressed constantly even at P-deficient conditions. The transcription of cyr genes at P-replete conditions or after P supplementation increased from 1.18-fold to 8.33-fold. In conclusion, C. raciborskii may rapidly reorganize metabolic processes as an adaptive response to environmental P fluctuations. CYN production and cyr gene expression were constitutive metabolic processes in toxic C. raciborskii.