Corydalis yanhusuo extract and its pharmacological substances alleviate food allergy by inhibiting mast cells activation via PLC/PKC/STAT3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Food allergies have increasingly become a disease that affects global health and need for corresponding therapeutic drugs urgently. As a traditional Chinses medicine with a wide range of pharmacological effects, however, there was no clear research confirming therapeutic effect and pharmacological substances of Corydalis yanhusuo (YHS) on food allergies. Mast cells (MCs) are the main effector cells which mediate allergic and pseudo-allergic reactions. MATERIALS AND METHODS: In this study, we investigated the effect of YHS extract on treating food allergy and its underlying mechanism. The inhibitory effect of YHS on MCs activation in vitro was evaluated by Ca2+ influx, degranulation, and cytokine release detection. The in vivo effect was investigated using the passive cutaneous anaphylaxis (PCA), active systemic allergy as well as OVA-induced food allergy mice. Western blot was performed to reveal the signaling pathway. RESULTS: YHS extract showed an inhibitory effect on MCs activation and food allergy both in vitro and in vivo. PLC/PKC/STAT3 signaling pathway was suppressed by YHS extract in the disease. HPLC analysis revealed YHS extract contains corydaline and tetrahydropalmatine, and both compounds inhibited MCs activation induced by C48/80 in vitro. CONCLUSION: YHS extract inhibited the MCs activation and food allergy via PLC/PKC/STAT3 pathway.

Inhibition of pseudo-allergic reactions by vitamin K3 directly targeting GAB1 in mast cells.

BACKGROUND: Vitamin K3 (VK3), a fat-soluble synthetic analog of the vitamin K family, has coagulant, anti-inflammatory, antibacterial, and anticancer properties. Pseudo allergy is a IgE-independent immune response associated with mast cells. This study investigated the role of VK3 in IgE-independent mast cell activation. METHODS: Substance P (SP) was used to induce LAD2-cell activation in order to analyze the effects of VK3 in vitro. Cutaneous allergy and systemic allergy mouse models were used to analyze the anti-pseudo-allergic effects of VK3. Proteome microarray assays were used to analyze VK3-binding protein. Biolayer interferometry and immunoprecipitation were used to verify interaction between VK3 and its key targets. RNA interference was used to determine the role of GAB1 in LAD2cell activation. RESULTS: VK3 inhibited SP-induced LAD2-cell activation, and resulted in the release of ß-hexosaminidase, histamine and cytokines; VK3 inhibited SP-induced pseudo allergic reactions in mice, and serum histamine and TNF-α levels decreased. Degranulation of skin mast cells was reduced; GAB1 in mast cells was stably bound to VK3. GAB1 participated in SP-induced LAD2-cell activation. GAB1 knockdown in LAD2 cells prevented SP-induced ß-hexosaminidase release, calcium mobilization and cell skeletal remodeling. VK3 directly binds to GAB1 and reduces its expression to inhibited SP-induced LAD2 cell activation. CONCLUSION: The anti-pseudo-allergic activity of VK3 was confirmed in vitro and in vivo. VK3 can inhibit SP-induced mast cell activation by directly targeting GAB1. This study provides new insights on the activity of VK3 and the mechanism of pseudoallergic reaction.

Genomic Analysis of Leptolyngbya boryana CZ1 Reveals Efficient Carbon Fixation Modules.

Cyanobacteria, one of the most widespread photoautotrophic microorganisms on Earth, have evolved an inorganic CO2-concentrating mechanism (CCM) to adapt to a variety of habitats, especially in CO2-limited environments. Leptolyngbya boryana, a filamentous cyanobacterium, is widespread in a variety of environments and is well adapted to low-inorganic-carbon environments. However, little is currently known about the CCM of L. boryana, in particular its efficient carbon fixation module. In this study, we isolated and purified the cyanobacterium CZ1 from the Xin'anjiang River basin and identified it as L. boryana by 16S rRNA sequencing. Genome analysis revealed that L. boryana CZ1 contains ß-carboxysome shell proteins and form 1B of Rubisco, which is classify it as belonging to the ß-cyanobacteria. Further analysis revealed that L. boryana CZ1 employs a fine CCM involving two CO2 uptake systems NDH-13 and NDH-14, three HCO3- transporters (SbtA, BicA, and BCT1), and two carboxysomal carbonic anhydrases. Notably, we found that NDH-13 and NDH-14 are located close to each other in the L. boryana CZ1 genome and are back-to-back with the ccm operon, which is a novel gene arrangement. In addition, L. boryana CZ1 encodes two high-affinity Na+/HCO3- symporters (SbtA1 and SbtA2), three low-affinity Na+-dependent HCO3- transporters (BicA1, BicA2, and BicA3), and a BCT1; it is rare for a single strain to encode all three bicarbonate transporters in such large numbers. Interestingly, L. boryana CZ1 also uniquely encodes two active carbonic anhydrases, CcaA1 and CcaA2, which are also rare. Taken together, all these results indicated that L. boryana CZ1 is more efficient at CO2 fixation. Moreover, compared with the reported CCM gene arrangement of cyanobacteria, the CCM-related gene distribution pattern of L. boryana CZ1 was completely different, indicating a novel gene organization structure. These results can enrich our understanding of the CCM-related gene arrangement of cyanobacteria, and provide data support for the subsequent improvement and increase in biomass through cyanobacterial photosynthesis.

Effects of climate change and human activities on vegetation coverage change in northern China considering extreme climate and time-lag and -accumulation effects.

Quantifying the contributions of climate change (CC) and human activities (HA) to vegetation change is crucial for making a sustainable vegetation restoration scheme. However, the effects of extreme climate and time-lag and -accumulation effects on vegetation are often ignored, thus underestimating the impact of CC on vegetation change. In this study, the spatiotemporal variation of fractional vegetation cover (FVC) from 2000 to 2019 in northern China (NC) as well as the time-lag and -accumulation effects of 15 monthly climatic indices, including extreme indices, on the FVC, were analyzed. Subsequently, a modified residual analysis considering the influence of extreme climate and time-lag and -accumulation effects was proposed and used to attribute the change in the FVC contributed by CC and HA. Given the multicollinearity of climatic variables, partial least squares regression was used to construct the multiple linear regression between climatic indices and the FVC. The results show that: (1) the annual FVC significantly increased at a rate of 0.0268/10a from 2000 to 2019 in all vegetated areas of NC. Spatially, the annual FVC increased in most vegetated areas (∼81.6 %) of NC, and the increase was significant in ∼54.6 % of the areas; (2) except for the temperature duration (DTR), climatic indices had no significant time-lag effects but significant time-accumulation effects on the FVC change. The DTR had both significant time-lag and -accumulation effects on the FVC change. Except for potential evapotranspiration and DTR, the main temporal effects of climatic indices on the FVC were a 0-month lag and 1-2-month accumulation; and (3) the contributions of CC and HA to FVC change were 0.0081/10a and 0.0187/10a in NC, respectively, accounting for 30.2 % and 69.8 %, respectively. HA dominated the increase in the FVC in most provinces of NC, except for the Qinghai and Neimenggu provinces.