TrxR1

This study aimed to explore the role of melatonin in oxidative stress-induced injury on retinal ganglion cells and the underlying mechanisms. The immortalized RGC-5 cells were treated with H₂O₂ to induce oxidative injury. Cell viability was measured by Cell Counting Kit-8, and apoptosis was determined by flow cytometry and western blot assays. Reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels were examined to evaluate oxidative stress levels. In addition, Thioredoxin-1 (Trx1) was silenced in RGC-5 cells using small interfering RNA followed by signaling pathway examination to explore the underlying mechanisms of melatonin in alleviating oxidative injury. Melatonin pre-treatment significantly alleviated H₂O₂-induced apoptosis in RGC-5 cells. Melatonin also markedly reversed the upregulation of cleaved-caspase 3, cleaved-caspase 9, and Bax expression and downregulation of Bcl-2 expression induced by H₂O₂. Further analyses presented that melatonin significantly attenuated the increase of ROS, LDH, and MDA levels in RGC-5 cells after H₂O₂ treatment. Melatonin also abolished the downregulated expression of Superoxide dismutase type 1, Trx1, and Thioredoxin reductase 1, and the reduced activity of thioredoxin reductase in RGC-5 cells after H₂O₂ treatment. Notably, Trx1 knockdown significantly mitigated the protective effect of melatonin in alleviating H₂O₂-induced apoptosis and oxidative stress, while administration of compound C, a common inhibitor of c-Jun N-terminal kinase (JNK) signaling, partially reversed the effect of Trx1 silencing, thereby ameliorating the apoptosis and oxidative injury induced by H₂O₂ in RGC-5 cells. Melatonin could significantly alleviate oxidative stress-induced injury of retinal ganglion cells via modulating Trx1-mediated JNK signaling pathway.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and is a serious threat to human health; thus, early diagnosis and adequate treatment are essential. However, there are still great challenges in identifying the tipping point and detecting early warning signals of early HCC. In this study, we aimed to identify the tipping point (critical state) of and key molecules involved in hepatocarcinogenesis based on time series transcriptome expression data of HCC patients. The phase from veHCC (very early HCC) to eHCC (early HCC) was identified as the critical state in HCC progression, with 143 genes identified as key candidate molecules by combining the DDRTree (dimensionality reduction via graph structure learning) and DNB (dynamic network biomarker) methods. Then, we ranked the candidate genes to verify their mRNA levels using the diethylnitrosamine (DEN)-induced HCC mouse model and identified five early warning signals, namely, CCT3, DSTYK, EIF3E, IARS2 and TXNRD1; these signals can be regarded as the potential early warning signals for the critical state of HCC. We identified CCT3 as an independent prognostic factor for HCC, and functions of CCT3 involving in the "MYCtargets_V1" and "E2F-Targets" are closely related to the progression of HCC. The predictive method combining the DDRTree and DNB methods can not only identify the key critical state before cancer but also determine candidate molecules of critical state, thus providing new insight into the early diagnosis and preemptive treatment of HCC.

The oxidative stress induced by ultraviolet (UV) radiation is a pivotal factor in skin aging and can even contribute to the development of skin cancer.

This study explored the antioxidant effect and mechanism of water-soluble intracellular extract (WIE) of Desmodesmus sp.YT (YT), aiming to develop a natural antioxidant suitable for incorporation into cosmetics.

The study evaluated the scavenging capacity of YT-WIE against free radicals and assessed its impact on human skin fibroblasts (HSF) cell viability and UV resistance using Cell Counting Kit-8 (CCK-8). Transcriptome sequencing was employed to elucidate the mechanism of action, while RT-qPCR and western blot were used to validate the expression of key genes.

YT-WIE displayed robust antioxidant activity, demonstrating potent scavenging abilities against 2,2-diphenyl-1-picrylhydrazyl (DPPH; IC50 = 0.55 mg mL^-1 ), 2,2'-Azino-bis (3 ethylbenzothiazoline-6-sulfonic acid; ABTS; IC50 = 3.11 mg mL^-1 ), Hydroxyl (·OH; IC50 = 2.21 mg mL^-1 ), and Superoxide anion (O₂ ^•- ; IC50 = 0.98 mg mL^-1 ). Furthermore, compared to the control group, the YT-WIE group exhibited an 89.30% enhancement in HSF viability and a 44.63% increase in survival rate post-UV irradiation. Significant upregulation of antioxidant genes (GCLC, GCLM, TXNRD1, HMOX1, NQO1) was observed with YT-WIE treatment at 400 μg mL^-1 , with fold increases ranging from 1.13 to 5.85 times.

YT-WIE demonstrated considerable potential as an antioxidant, shielding human cells from undue oxidative stress triggered by external stimuli such as UV radiation. This suggests its promising application in cosmetics antioxidants.