Danggui-Shaoyao San alleviates cognitive impairment via enhancing HIF-1α/EPO axis in vascular dementia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Invigorating blood circulation to remove blood stasis is a primary strategy in TCM for treating vascular dementia (VaD). Danggui-Shaoyao San (DSS), as a traditional prescription for neuroprotective activity, has been proved to be effective in VaD treatment. However, its precise molecular mechanisms remain incompletely understood. AIM OF THE STUDY: The specific mechanism underlying the therapeutic effects of DSS on VaD was explored by employing network pharmacology as well as in vivo and in viro experiment validation. MATERIALS AND METHODS: We downloaded components of DSS from the BATMAN-TCM database for target prediction. The intersection between the components of DSS and targets, PPI network, as well as GO and KEGG enrichment analysis were then performed. Subsequently, the potential mechanism of DSS predicted by network pharmacology was assessed and validated through VaD rat model induced by 2VO operation and CoCl2-treated PC12 cells. Briefly, the DSS extract were first quantified by HPLC. Secondly, the effect of DSS on VaD was studied using MWM test, HE staining and TUNEL assay. Finally, the molecular mechanism of DSS against VaD was validated by Western blot and RT-QPCR experiments. RESULTS: Through network analysis, 137 active ingredients were obtained from DSS, and 67 potential targets associated with DSS and VaD were identified. GO and KEGG analysis indicated that the action of DSS on VaD primarily involves hypoxic terms and HIF-1 pathway. In vivo validation, cognitive impairment and neuron mortality were markedly ameliorated by DSS. Additionally, DSS significantly reduced the expression of proteins related to synaptic plasticity and neuron apoptosis including PSD-95, SYP, Caspase-3 and BCL-2. Mechanistically, we confirmed DSS positively modulated the expression of HIF-1α and its downstream proteins including EPO, p-EPOR, STAT5, EPOR, and AKT1 in the hippocampus of VaD rats as well as CoCl2-induced PC12 cells. HIF-1 inhibitor YC-1 significantly diminished the protection of DSS on CoCl2-induced PC12 cell damage, with decreased HIF-1α, EPO, EPOR expression. CONCLUSION: Our results initially demonstrated DSS could exert neuroprotective effects in VaD. The pharmacological mechanism of DSS may be related to its positive regulation on HIF-1α/EPO pathway.

Spatio-temporal variation in soil thermal conductivity during the freeze-thaw period in the permafrost of the Qinghai-Tibet Plateau in 1980-2020.

The Qinghai-Tibet Plateau (QTP) has the largest amount of permafrost in the low and middle latitudes, making it highly susceptible to the effects of global warming. In particular, the degradation of permafrost can be intensified by anomalous amplified warming. To accurately model the hydrothermal dynamics of permafrost and its future trends, the accumulation of high-precision, long-term data for the soil thermal conductivity (STC) in the active layer is crucial. However, no previous research has systematically investigated the spatio-temporal variation in the STC on the QTP over an extended period. Therefore, this study aims to fill this gap using the XGBoost model to analyze the STC in the permafrost on the QTP from 1980 to 2020. The findings of this study provide some preliminary insights. First, areas with high variation in the STC between the freeze-thaw periods over the 40 years gradually migrated from the western region to the central region. Second, since 2015, STC in more than 90 % of the permafrost region in the thawing period has shown positive growth. While, during the freezing period, the STC also exhibited an increase over most regions of the QTP, though the western region and parts of the northeastern region exhibited a decrease. Third, the spatial center of gravity for the STC during the freezing and thawing periods from 1980 to 2020 shifted. The mean STC was larger in the eastern and northeastern regions during the freezing period and larger in the western region during the thawing period. Fourth, both alpine swamp meadow and alpine meadow exhibited a gradual increase in the STC during the freeze-thaw period from 1980 to 2020. The conclusions and data products from this study are expected to support spatiotemporal modeling of the permafrost on the QTP and assist in the prognosis for its future.

Ethylene carbodiimide-fixed donor splenocytes combined with cordycepin induce long-term protection to mice cardiac allografts.

Infusion of ethylene carbodiimide-fixed donor splenocytes (ECDI-SPs) is an effective method to induce donor-specific protection to allografts. However, the ischemia reperfusion (I/R) injury during transplant leads to abundant of pro-inflammatory cytokines, which negates the effect of ECDI-SPs. Therefore, suppressing pro-inflammatory cytokine secretion while promoting anti-inflammatory cytokine release would enhance the graft protective efficacy of ECDI-SPs. In this study, we aimed to determine the effect of ECDI-SPs combined with a short course of cordycepin (an anti-inflammatory agent) on the long-term outcomes of mice cardiac allografts. Our results demonstrated that ECDI-SPs combined with cordycepin significantly promoted mice cardiac allograft survival compared with ECDI-SPs monotherapy. This effect was accompanied by decreased production of pro-inflammatory cytokines (IL-1ß, IL-6, IL-17 and TNFα), increased secretion of anti-inflammatory cytokines (IL-10 and TGFß), inhibition of Th17 and expansion of Tregs, and prevention of I/R injury. We concluded that cordycepin appeared to enhance the effect of modulating cytokine profile and regulate the Teff:Treg balance so as to strengthen the graft protective effect of ECDI-SPs. Our study of ECDI-SPs combined with cordycepin may provide a promising approach for prolong allograft survival.