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Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, diabetes belongs to the category of "emaciation-thirst disease" in traditional Chinese medicine (TCM). Bushen Huoxue Prescription (BHP) is composed of traditional Chinese materia medica, which has therapeutic effects on DR and early diabetic retinal edema (EDRE). However, the therapeutic mechanism is unclear. Exploring the mechanism of BHP against EDRE. Feeding Sprague Dawley (SD) rats a high-fat, high-sugar diet as well as providing intraperitoneal injections of streptozotocin (STZ) to promote inner blood-retinal barrier (iBRB) damage that can trigger EDRE, evaluating the therapeutic effect of BHP by the level of expressiveness of TJ proteins (ZO-1,Occludin) of the iBRB and the leakage of rhodamine B isothiocyanate (RITC) in the retina. The combination of network pharmacology and metabolomics was employed to study the mechanism of BHP in preventing of EDRE, then four proteins which were closely to the damage of iBRB were chosen for the validation by employing Western Blot (WB). Research of network pharmacology had shown that BHP had efficacy against EDRE by regulating targets such as AKT1, ALB, TNF, PPARG, etc, its potential pathways mainly involving signaling pathways such as HIF-1. In untargeted metabolomics analysis of serum, 15 differential metabolites were identified, with the metabolic pathways focusing on ketone body metabolism and synthesis, sphingolipid metabolism and phenylalanine metabolism. The conclusions of metabolomics and network pharmacology revealed that BHP can treat EDRE by alleviating hypoxia and oxidative stress and exerting protection of the iBRB. Finally, BHP's protection behavior of the iBRB was validated by WB experiments. Through integrating pharmacodynamics, network pharmacology and metabolomics, BHP was discovered to have a crucial function in EDRE therapy by preserving the integrity of iBRB. This comprehensive strategy also provided a reasonable way to reveal the multi-components, multi-targets, multi-pathways mechanism of TCM. [Display omitted] • Presentation of "early diabetic retinal edema" as a crucial therapeutic point. • Dyslipidemia is believed to play a significant influence in the progression of EDRE. • The mechanism of BHP anti-EDRE was studied. [ABSTRACT FROM AUTHOR]

The association between PM 2.5 (particulate matter ≤ 2.5 µm) short-term exposure and its health effect is non-linear from the epidemiological studies. And this nonlinearity is suggested to be related with the PM 2.5 heterogeneity, however, the underlying biological mechanism is still unclear. Here, a total of 38 PM 2.5 filters were collected continuously for three weeks in winter Beijing, with the ambient PM 2.5 varying between 10 and 270 µg/m3. Human monocytes-derived macrophages (THP-1) were treated with PM 2.5 water-soluble elutes at 10 µg/mL to investigate the PM 2.5 short-term exposure effect from a proinflammatory perspective. The proinflammatory cytokine tumor necrosis factor (TNF) induced by the PM 2.5 elutes at equal concentrations were unequal, showing the heterogeneity of PM 2.5 proinflammatory potentials. Of the various chemical and biological components, lipopolysaccharide (LPS) showed a strong positive association with the TNF heterogeneity. However, some outliers were observed among the TNF-LPS association. Specifically, for PM 2.5 from relatively clean air episodes, the higher LPS amount corresponded to relatively low TNF levels. And this phenomenon was also observed in the promotion tests by treating macrophages with PM 2.5 elutes dosed with additional trace LPS. Gene expression analysis indicated the involvement of oxidative-stress related genes in the LPS signaling pathway. Therefore, a potential oxidative-stress-mediated suppression on the PM 2.5 -borne LPS proinflammatory effect was proposed to be accounted for the outliers. Overall, the results showed the differential role of LPS in the heterogeneity of PM 2.5 proinflammatory effects from a component-based perspective. Future experimental studies are needed to elucidate the signaling pathway of LPS attached on PM 2.5 from different air quality episodes. [Display omitted] [ABSTRACT FROM AUTHOR]

• IL-11 directly protects neuronal cells from oxidative damage caused by H 2 O 2 and reduces neuronal apoptosis. • Transcriptome analysis suggests that the JAK/STAT pathway may be involved in the antioxidant activity of IL-11. • Rescue experiments and animal models demonstrated that IL-11 prevented neuronal apoptosis caused by oxidative imbalance through activation of the JAK/STAT signaling pathway and promoted the recovery of motor function in SCI rats. Excess reactive oxygen species (ROS) generated by oxidative stress is a crucial factor affecting neuronal dysfunction after spinal cord injury (SCI). IL-11 has been reported to have antioxidative stress capacity. In the present study, we investigated the protective effect and mechanism of IL-11 against neuronal cell damage caused by oxidative imbalance. We established a H 2 O 2 -induced oxidative stress injury model in PC12 cells and observed the effects of IL-11 on cellular activity, morphology, oxidase and antioxidant enzymes, and ROS release. Furthermore, the effect of IL-11 on apoptosis of PC12 cells was assessed by flow cytometry, a TUNEL assay and Western blotting. Transcriptome analysis and rescue experiments revealed the mechanism by which IL-11 protects neurons from oxidative stress damage. For the in vivo investigation, an adenovirus-mediated IL-11 overexpression SCI rat model was constructed to validate the beneficial effect of IL-11 against SCI. IL-11 significantly improved the viability and enhanced the antioxidant activity of H 2 O 2 -treated PC12 cells while reducing ROS release. In addition, IL-11 reduced H 2 O 2 -induced PC12 cell apoptosis. Transcriptome analysis revealed that the JAK/STAT pathway may be related to the antioxidant activity of IL-11. Treatment with a JAK/STAT inhibitor (Stattic) exacerbated the oxidative damage induced by H 2 O 2 and attenuated the protective effects of IL-11. The results of in vivo studies showed that IL-11 prevented neuronal apoptosis due to oxidative imbalance and promoted the restoration of motor function in SCI rats by activating the JAK/STAT signaling pathway. IL-11 inhibited oxidative stress-induced neuronal apoptosis at least in part by activating the JAK/STAT signaling pathway and further promoted the recovery of motor function. These findings suggest that IL-11 may be an effective target for the treatment for SCI. [ABSTRACT FROM AUTHOR]