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Radiotherapy for head and neck tumors can lead to a severe complication known as radiation-induced brain injury (RIBI). However, the underlying mechanism of RIBI development remains unclear, and limited prevention and treatment options are available. Neuroactive steroids have shown potential in treating neurological disorders. 5α-Androst-3β, 5, 6β-triol (TRIOL), a synthetic neuroprotective steroid, holds promise as a treatment candidate for RIBI patients. However, the neuroprotective effects and underlying mechanism of TRIOL on RIBI treatment are yet to be elucidated. In the present study, our findings demonstrate TRIOL's potential as a neuroprotective agent against RIBI. In gamma knife irradiation mouse model, TRIOL treatment significantly reduced brain necrosis volume, microglial activation, and neuronal loss. RNA-sequencing, immunofluorescence, real-time quantitative polymerase chain reaction, siRNA transfection, and western blotting techniques revealed that TRIOL effectively decreased microglial activation, proinflammatory cytokine release, neuron loss, and guanylate-binding protein 5 (GBP5) expression, along with its downstream signaling pathways NF-κB and NLRP3 activation in vitro. In summary, TRIOL effectively alleviate RIBI by inhibiting the GBP5/NF-κB/NLRP3 signal axis, reducing microglia activation and pro-inflammation cytokines release, rescuing neuron loss. This study highlights the potential of TRIOL as a novel and promising therapy drug for RIBI treatment.

01 Mar 2024·International Immunopharmacology

Synthetic steroid of 5α-Androst-3β,5α,6β-Triol alleviates acute lung injury via inhibiting inflammation and oxidative stress

Article

Author: Hu, Cheng ; Li, ShengLong ; Ouyang, Ying ; Wu, JiaXin ; Lu, BingZheng ; Liu, Ying ; Ding, YuXuan ; Chen, Chen ; Chen, YuPin ; Hong, ShiRan ; Liang, HuaFeng ; Zhou, YuWei ; Yin, Wei

Acute lung injury (ALI) is a severe and potentially fatal respiratory condition with limited treatment options. The pathological evolution of ALI is driven by persistent inflammation, destruction of the pulmonary vascular barrier and oxidative stress. Evidence from prior investigations has identified 5α-androst-3β,5α,6β-Triol (TRIOL), a synthetic analogue of the naturally occurring neuroprotective compound cholestane-3β,5α,6β-triol, possesses notable anti-inflammatory and antioxidative properties. However, the precise effects of TRIOL on alleviating lung injury along with the mechanisms, have remained largely unexplored. Here, TRIOL exhibited pronounced inhibitory actions on lipopolysaccharide (LPS)-induced inflammation and oxidative stress damage in both lung epithelial and endothelial cells. This protective effect is achieved by its ability to mitigate oxidative stress and restrain the inflammatory cascade orchestrated by nuclear factor-kappa B (NF-κB), thereby preserving the integrity of the pulmonary epithelial barrier. We further validated that TRIOL can attenuate LPS-induced lung injury in rats and mice by reducing inflammatory cell infiltration and improving pulmonary edema. Furthermore, TRIOL decreased the pro-inflammatory factors and increased of anti-inflammatory factors induced by LPS. In conclusion, our study presents TRIOL as a promising novel candidate for the treatment of ALI.

01 Jan 2021·Zoological ResearchQ1 · BIOLOGY

Author Correction: Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

Q1 · BIOLOGY

ArticleOA

Author: Tang, Zhong-Wei ; N Cooper, David ; Zhang, Jing-Xia ; Guo, Chun-Xue ; Zhang, Guo-Jie ; Zhu, Wen-Bo ; Gao, Yu-Qi ; Qiu, Bi-Tao ; Yan, Min ; Yan, Guang-Mei ; Zhang, Pei ; Yang, Huan-Ming ; Wang, Jian ; Zhan, Xiao-Yu ; Wang, You-Qiong ; Gao, Yi-Xing ; Yuan, Zhi-Bing ; Li, Yuan ; Lu, Bing-Zheng ; Huang, Yi-Jun ; Li, Qi-Ye ; Chen, Jie-Si ; Sheng, Long-Xiang ; Liu, Fu-Yu ; Yin, Wei ; Xu, Gang ; Lin, Sui-Zhen

Following the publication of our paper (Zhang et al., 2020), it has come to our attention that we erroneously listed two funding sources unrelated to this study in the "ACKNOWLEDGEMENTS" section. Hereby, we wish to update the "ACKNOWLEDGEMENTS" section as a correction.

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Pipeline

Pipeline Snapshot as of 16 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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