Insights into the mechanism of action of pterostilbene against influenza A virus-induced acute lung injury.

BACKGROUND: Severe respiratory system illness caused by influenza A virus infection is associated with excessive inflammation and abnormal apoptosis in alveolar epithelial cells (AEC). However, there are limited therapeutic options for influenza-associated lung inflammation and apoptosis. Pterostilbene (PTE, trans-3,5-dimethoxy-4-hydroxystilbene) is a dimethylated analog of resveratrol that has been reported to limit influenza A virus infection by promoting antiviral innate immunity, but has not been studied for its protective effects on virus-associated inflammation and injury in AEC. PURPOSE: Our study aimed to investigate the protective effects and underlying mechanisms of PTE in modulating inflammation and apoptosis in AEC, as well as its effects on macrophage polarization during influenza virus infection. STUDY DESIGN AND METHODS: A murine model of influenza A virus-mediated acute lung injury was established by intranasal inoculation with 5LD50 of mouse-adapted H1N1 viruses. Hematoxylin and eosin staining, immunofluorescence, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blotting, Luminex and flow cytometry were performed. RESULTS: PTE effectively mitigated lung histopathological changes and injury induced by H1N1 viruses in vivo. These beneficial effects of PTE were attributed to the suppression of inflammation and apoptosis in AEC, as well as the modulation of M1 macrophage polarization. Mechanistic investigations revealed that PTE activated the phosphorylated AMP-activated protein kinase alpha (P-AMPKα)/sirtui1 (Sirt1)/PPARγ coactivator 1-alpha (PGC1α) signal axis, leading to the inhibition of nuclear factor kappa-B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling induced by H1N1 viruses, thereby attenuating inflammation and apoptosis in AEC. PTE also forced activation of the P-AMPKα/Sirt1/PGC1α signal axis in RAW264.7 cells, counteracting the activation of phosphorylated signal transducer and activator of transcription 1 (P-STAT1) induced by H1N1 viruses and the augment of P-STAT1 activation in RAW264.7 cells with interferon-gamma (IFN-γ) pretreatment before viral infection, thereby reducing H1N1 virus-mediated M1 macrophage polarization as well as the enhancement of macrophages into M1 phenotypes elicited by IFN-γ pretreatment. Additionally, the promotion of the transition of macrophages towards the M2 phenotype by PTE was also related to activation of the P-AMPKα/Sirt1/PGC1α signal axis. Moreover, co-culturing non-infected AEC with H1N1 virus-infected RAW264.7 cells in the presence of PTE inhibited apoptosis and tight junction disruption, which was attributed to the suppression of pro-inflammatory mediators and pro-apoptotic factors in an AMPKα-dependent manner. CONCLUSION: In conclusion, our findings suggest that PTE may serve as a promising novel therapeutic option for treating influenza-associated lung injury. Its ability to suppress inflammation and apoptosis in AEC, modulate macrophage polarization, and preserve alveolar epithelial cell integrity highlights its potential as a therapeutic agent in influenza diseases.

Preparation of black phosphorus@sodium alginate microspheres with bone matrix vesicle structure via electrospraying for bone regeneration.

Bone matrix vesicles are commonly acknowledged as the primary site of biomineralization in human skeletal tissue. Black phosphorus has exhibited favorable properties across various chemical and physical domains. In this investigation, a novel composite microsphere was synthesized through the amalgamation of sodium alginate (ALG) with black phosphorus nanosheets (BP) utilizing the electrospray (ES) technique. These microspheres were tailored to mimic the regulatory function of matrix vesicles (MV) upon exposure to a biomimetic mineralization fluid (SBF) during the biomineralization process. Results revealed that black phosphorus nanosheets facilitated the generation of hydroxyapatite (HA) on the microsphere surface. Live-dead assays and cell proliferation experiments showcased a cell survival rate exceeding 85 %. Moreover, wound healing assessments unveiled that M-ALG-BP microspheres exhibited superior migration capacity, with a migration rate surpassing 50 %. Furthermore, after 7 days of osteogenic induction, M-ALG-BP microspheres notably stimulated osteoblast differentiation. Particularly noteworthy, M-ALG-BP microspheres significantly enhanced osteogenic differentiation of osteoblasts and induced collagen production in vitro. Additionally, experiments involving microsphere implantation into mouse skeletal muscle demonstrated the potential for ectopic mineralization by ALG-BP microspheres. This investigation underscores the outstanding mineralization properties of ALG-BP microspheres and their promising clinical prospects in bone tissue engineering.

The influence of dietary Coenzyme Q10 on growth performance, antioxidant capacity and resistance against Aeromonas hydrophila of juvenile European eel (Anguilla anguilla).

The present study was conducted to investigate the effects of dietary Coenzyme Q10 (CoQ10) on the growth performance, body composition, digestive enzyme activity, antioxidant capacity, intestinal histology, immune-antioxidant gene expression and disease resistance of juvenile European eel (Anguilla anguilla). Fish were fed a diet supplemented with CoQ10 at concentrations of 0, 40, 80 and 120 mg/kg for 56 days. The results indicated that dietary CoQ10 supplementation did not significantly affect final body weight (FBW), survival rate (SR), weight gain (WG), feed rate (FR), viscerosomatic index (VSI) or hepatosomatic index (HSI) among all experimental groups. However, the highest FBW, WG and SR were found in the 120 mg/kg CoQ10 group. Dietary 120 mg/kg CoQ10 markedly improved feed efficiency (FE) and the protein efficiency ratio (PER). The crude lipid in the body and triglycerides (TG) and total cholesterol (TC) in serum were obviously lower in the 120 mg/kg CoQ10 group than in the control group. For digestive enzymes, protease activity in the intestine was markedly boosted in the 120 mg/kg CoQ10 group. The serum activities of SOD, CAT and GST in the 120 mg/kg CoQ10 group were significantly higher than those in the control group. Dietary 120 mg/kg CoQ10 efficiently enhanced superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities in the liver, while the malondialdehyde (MDA) content was significantly decreased. No significant histological changes in the liver were identified in any group. Dietary supplementation with 120 mg/kg CoQ10 improved antioxidant capacity and immunity by upregulating the expression of cyp1a, sod, gst, lysC, igma1, igmb1 and irf3 in the liver. Furthermore, the cumulative survival rate of juvenile European eel against challenge with Aeromonas hydrophila was significantly elevated in the 80 and 120 mg/kg CoQ10 supplemented groups. Conclusively, our study suggested that supplementing the diet of juvenile European eel with CoQ10 at a concentration of 120 mg/kg could promote their feed utilization, fat reduction, antioxidant capacity, digestibility, immune-antioxidant gene expression and resistance to Aeromonas hydrophila without negative effects on fish health status.

The effect of transcutaneous auricular vagus nerve stimulation on HRV in healthy young people.

Transcutaneous auricular vagus nerve stimulation (taVNS) has shown positive effects on a variety of diseases. Considering that decreased heart rate variability (HRV) is closely associated with morbidity and mortality for a variety of diseases, it is important to investigate the effect of taVNS on HRV. In Study 1, we conducted a two-stage cross-over trial to compare the effects of taVNS and sham taVNS (staVNS) on HRV. In Study 2, we systematically tested the effects of different taVNS parameters on high frequency (HF) component of HRV. The results showed that taVNS significantly increased measurements of root mean square of the difference between successive RR intervals (RMSSD), percentage of number of pairs of adjacent RR intervals differing greater than 50ms (pRR50), standard deviation of all RR intervals (SDRR), HF. Significantly, enhancement of HF and pRR50 persisted into recovery period. In addition, higher baseline LF/HF ratio was associated with greater LF/HF ratio decrease. Findings also showed that there was no significant difference in measurements of HF between different taVNS parameters. These studies suggest that taVNS could increase HRV, it may help taVNS in the treatment of low HRV related diseases. However, taVNS may not have parameter-specific effects on HRV.