Biancaea decapetala (Roth) O.Deg. extract exerts an anti-inflammatory effect by regulating the TNF/Akt/NF-κB pathway.

BACKGROUND: Biancaea decapetala (Roth) O.Deg. (Fabaceae) is used to treat colds, fever, and rheumatic pain caused by inflammation. However, the mechanism underlying its anti-inflammatory properties remains unclear. PURPOSE: This study aimed to evaluate the anti-inflammatory activity of Biancaea decapetala extract (BDE) in vitro and in vivo and explore the possible underlying mechanism and potential targets. METHODS: The release of nitric oxide (NO) and inflammatory cytokines in LPS-stimulated RAW264.7 cells and rats were measured using Griess reagent and enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was employed to examine the pathology of animal tissues. Transcriptome analysis was performed to screen the pathways related to BDE-mediated inhibition of inflammation, and the expression of related proteins was measured using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, ELISA, and immunofluorescence methods. Surface Plasmon Resonance (SPR) and the Drug Affinity Reaction Target Stability (DARTS) method were used to verify whether BDE binds to TNF-α target protein, while a L929 cell model and NF-κB gene reporter systematic method were used to investigate the inhibitory effect of BDE on the activity of TNF-α protein. RESULTS: BDE inhibited the expression of TNF-α, IL-1ß, IL-6, and NO in RAW264.7 cells and rats, and improved the pathological changes in lung tissue. RNA-seq showed that BDE may regulate the TNF/Akt/NF-κB pathway to inhibit inflammation onset. BDE significantly downregulated the mRNA expression of TNF-α, IL-6, IL-1ß, and that of relevant proteins, including TNF-α, p-p65, p-Akt, p-IκBα. Furthermore, BDE inhibited the nuclear translocation of NF-κB (p65) and the activation of the Akt pathway by SC79. The L929 cell model, luciferase reporter gene analysis, DARTS, and SPR experiments showed that BDE may bind to TNF-α and inhibit the TNF-α-NF-κB pathway. CONCLUSION: BDE may target TNF-α to inhibit the TNF/Akt/NF-κB pathway, thereby attenuating inflammation. These findings reveal the anti-inflammatory effects and mechanisms of BDE and provide a theoretical basis for the further development and utilization of BDE.

Overexpression of the autophagy-related gene SiATG8a from foxtail millet (Setaria italica L.) in transgenic wheat confers tolerance to phosphorus starvation.

In plants, autophagy plays an important role in regulating intracellular degradation and amino acid recycling in response to nutrient starvation, senescence, and other environmental stresses. Foxtail millet (Setaria italica) shows strong resistance to various abiotic stresses; however, current understanding of the regulation network of abiotic stress resistance in foxtail millet remains limited. In this study, we aimed to determine the autophagy-related gene SiATG8a in foxtail millet. We found that SiATG8a was mainly expressed in the stem and was induced by low-phosphorus (LP) stress. Overexpression of SiATG8a in wheat (Triticum aestivum) significantly increased the grain yield and spike number per m2 under LP treatment compared to those in the WT varieties S366 and S4056. There was no significant difference in the grain P content between SiATG8a-overexpressing wheat and WT wheat under normal phosphorus (NP) and LP treatments. However, the phosphorus (P) content in the roots, stems, and leaves of transgenic plants was significantly higher than that in WT plants under NP and LP conditions. Furthermore, the expression of P transporter genes, such as TaPHR1, TaPHR3, TaIPS1, and TaPT9, in SiATG8a-transgenic wheat was higher than that in WT under LP. Collectively, overexpression of SiATG8a increases the P content of roots, stems, and leaves of transgenic wheat under LP conditions by modulating the expression of P-related transporter gene, which may result in increased grain yield; thus, SiATG8a is a candidate gene for generating transgenic wheat with improved tolerance to LP stress in the field.

Vitamin D deficiency relation to sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and duration of mechanical ventilation in critically ill children: A meta-analysis.

INTRODUCTION: Vitamin D deficiency in children is related to the augmented risk of bone illnesses, but its effect on critically ill children is still conflicting. This meta-analysis study was performed to assess the relationship between vitamin D deficiency in children and sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and duration of mechanical ventilation in critically ill children. METHODS: Through a systematic literature search up to June 2020, 16 studies with 2382 children, 1229 children of them with vitamin D deficiency, were found recording relationships between vitamin D deficiency and sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and/or duration of mechanical ventilation. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated between vitamin D deficiency children to non-vitamin D deficiency children on the different outcomes in critically ill children using the dichotomous or continuous methods with a random or fixed-effect model. RESULTS: The vitamin D deficiency children category had significantly higher sepsis (OR, 2.35; 95% CI, 1.19-4.63, P = .01); paediatric risk of mortality III score (OR, 2.19; 95% CI, 1.13-4.25, P = .02); higher length of hospital stay (OR, 4.26; 95% CI, 0.81-7.70, P = .02); higher duration of mechanical ventilation (OR, 1.89; 95% CI, 0.22-3.56, P = .03) compared with that in the non-vitamin D deficiency children. However, the need for ventilation support in vitamin D deficiency children did not significantly differ from non-vitamin D deficiency children (OR, 2.00; 95% CI, 0.98-4.07, P = .06) with relatively higher results in vitamin D deficiency children. CONCLUSIONS: Vitamin D deficiency in children might have an independent relationship with higher sepsis, paediatric risk of mortality III score, length of hospital stay, and duration of mechanical ventilation. The relation was relative with a higher risk in need for ventilation support with vitamin D deficiency children. This relationship encouraged us to recommend testing vitamin D levels in all critically ill children and providing them with supplemental vitamin D as prophylaxis.

The protective effect of Cordycepin on diabetic nephropathy through autophagy induction in vivo and in vitro.

BACKGROUND: Diabetic nephropathy (DN) is one of the most serious chronic complications of diabetes mellitus (DM). Autophagy is an important physiological function for podocytes to maintain stability of intracellular environment. In this study, we planned to clarify the effect of Cordycepin, a traditional Chinese medicine, on DN and the related mechanisms. METHODS: All rats were randomly divided into normal control group, diabetic controls, low-dose group (10 mg/kg), medium-dose group (100 mg/kg), and high-dose group (500 mg/kg). The level of cholesterol, blood sugar, triglyceride, creatinine, and urine protein was examined through an automatic biochemistry analyser. Enzyme-linked immunosorbent assay (Elisa) was used to detect the level of IL-1ß, IL-6, and IL-18. HE staining was used to examine histopathologic changes. TUNEL staining was used to detected cell apoptosis. The expression of fibrosis markers α-SMA, t-TG, and TIMP-1, apoptosis-related proteins cleaved-caspase3, Bax and Bcl-2, autophagy markers Beclin1, light chain 3 (LC3)I/II, and p62 were evaluated by western blot. RESULTS: The level of cholesterol, blood sugar, triglyceride, creatinine, and urine protein in the diabetic controls was much higher than that in the normal control group. Obvious histopathology injuries were also found in DN model group. After Cordycepin treatment, all the above indexes were improved compared with the DN group and tissue damages were also alleviated. Further studies showed that Cordycepin suppressed cell apoptosis and renal fibrosis and rescued cell autophagy in DN rat model. Moreover, the results of our in vitro experiments showed that the addition of 3-methyladenine (3-MA, specific autophagy inhibitor) successfully abolished the protective effect of Cordycepin on renal fibrosis through inducing apoptosis and renal fibrosis. The above protective effects of Cordycepin were exhibited in a dose-dependent manner. CONCLUSION: Cordycepin participated in the modulation of cell apoptosis, fibrosis, and autophagy induction in DN. Our study for the first time revealed that Cordycepin had a certain therapeutic effect on DN in rats through autophagy induction.