ß-Amyrin ameliorates pulmonary fibrosis by inhibiting inflammatory response and oxidative stress in mice.

The study aimed to determine efficacy and mechanisms of ß-Amyrin on pulmonary fibrosis. Use bleomycin (BLM) to induce the marine model of pulmonary fibrosis. ß-Amyrin (20, 40, 80 mg/kg) was once treated via intragastrical administration for five consecutive days when after BLM stimulation. HE/Masson staining, hydroxyproline (HYP) content, Arterial blood gas analysis (BGA), inflammatory cytokines and oxidative stress factors were performed in this study. The lung gas-exchange function was significantly improved after being treated ß-Amyrin with different concentrations, while IL-6, IL-1ß, TNF-α and MCP-1 levels were decreased. And the increased fibrotic lesion in lung was also determined after treatment of ß-Amyrin. Additionally, reduced MDA level and increase levels of GPX, SOD and GSH were also demonstrated using ß-Amyrin in BLM-induced mice in a dose-dependent manner. In conclusions, our study determined that ß-Amyrin has a potent efficacy in protecting against BLM-induced pulmonary fibrosis via suppressing inflammatory response and oxidative stress.

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study. / ä¸åŒç»´æŒå‰‚é‡æž¸æ©¼é ¸å’–å•¡å› å¯¹è¾ åŠ©é€šæ°”æ—©äº§å„¿çš„ç–—æ•ˆè¯„ä¼°ï¼šä¸€é¡¹åˆæ­¥å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

Albiflorin alleviates ovalbumin (OVA)-induced pulmonary inflammation in asthmatic mice.

In the present study, the effects of albiflorin (ALB) on the pulmonary inflammation induced by ovalbumin (OVA) in an asthmatic mouse model were investigated. Airway hyperreactivity (AHR) in asthmatic mice was detected using the acetylcholine stimulation test. Eosinophilia cells in the serum of asthmatic mice were counted. Hematoxylin and eosin (H&E) staining was used to observe pathological changes in lung tissue. Inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were detected in bronchoalveolar lavage fluid (BALF) and lung tissue using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) signaling pathway in the lungs of asthmatic mice. The results from the present study indicated that ALB dramatically suppressed the expression of inflammatory cytokines including IL-1ß, IL-6, and TNF-α, and inflammatory cells. In addition, ALB significantly decreased malondialdehyde (MDA) content as well as increased superoxide dismutase (SOD) activity. ALB also alleviated AHR in asthmatic mice and improved pathological changes in the lungs. In addition, ALB inhibited the MAPK/NF-κB signaling pathway in the lungs of the asthmatic mice. Thus, ALB appears to inhibit lung inflammation in asthmatic mice via regulation of the MAPK/NF-κB signaling pathway.

Computational design of peptide ligands to target the intermolecular interaction between viral envelope protein and pediatric receptor.

The recognition and binding of viral envelope protein to pediatric receptor subverts the membrane-trafficking apparatus to mediate virion export in young children. Here, we described a successful computational design of peptide ligands to target the intermolecular interaction between the virus large envelope protein (LHB) and adaptin receptor (ADT). Based on the crystal structure of ADT in complex with an oligopeptide segment corresponding to the core binding site of LHB, a sequence-specific amino acid preference profile was determined systematically for the ADT-binding peptides using structural bioinformatics approach. With the information harvested from the profile, a genetic evolution procedure was run to improve the biological potency of a peptide population generated randomly from the LHB. A number of potential hits were obtained from the evolution, and four were measured to interact with ADT at micromolar level. A high-affinity hit peptide was then optimized according to computational structural analysis. It is revealed that a potent peptide can be divided into three regions, i.e. a negatively charged region at N-terminus, a hydrophobic core region in middle, and a small, polar region at C-terminal tail. In addition, the two termini of peptide are partially out of the active pocket of ADT, thus contributing moderately to the peptide binding.

Fluoxetine, an Antidepressant Drug, Inhibited Cigarette Smoke-Induced Pulmonary Inflammation and Apoptosis in Rats.

The present study was designed to evaluate the anti-inflammatory effect of fluoxetine (Flu) against cigarette smoke (CS)-induced chronic obstructive pulmonary disease (COPD) in rats. Forty male Sprague-Dawley (SD) rats were randomly assigned to five groups: control group, CS group, dexamethasone (2 mg/kg) group, and flu (2 mg/kg). H&E staining demonstrated that Flu inhibited CS-induced pathological injury. In addition, Flu could restore the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. Flu also inhibited the levels of cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß). Furthermore, flu significantly inhibited the protein levels of TLR/NF-κB and apoptosis pathway in CS-induced rats. Our findings suggested that flu might effectively ameliorate the progression of COPD via inflammation and apoptosis pathway in rats.

Astragaloside IV ameliorates necrotizing enterocolitis by attenuating oxidative stress and suppressing inflammation via the vitamin D3-upregulated protein 1/NF-κB signaling pathway.

Astragaloside IV (AS-IV) is a flavonoid from the plant Astragalus membranaceus (Fisch) Bge that has a wide range of therapeutic effects. The aim of the present study was to examine the effect of AS-IV on rats with necrotizing enterocolitis (NEC) under oxidative stress and inflammation. Newborn Sprague-Dawley rats were induced with NEC by asphyxia and hypothermia applied on 3 consecutive days. The rats were orally administered AS-IV at 25, 50 and 75 mg/kg for 4 days. The results revealed that AS-IV administration prevented NEC-induced decrease in the concentration of malondialdehyde and myeloperoxidase, and increase in the activity of glutathione (GSH) and superoxide dismutase in murine models. AS-IV also inhibited NEC-induced elevation in the levels of interleukin (IL)-6, IL-1ß, tumor necrosis factor-α and nuclear factor (NF)-κB. The effects of AS-IV were achieved under inflammation and oxidative stress. Western blotting demonstrated that AS-IV substantially inhibited the phosphorylated (p)-IκBα, NF-κBp65, p-NF-κBp65 protein levels and increased vitamin D3 upregulated protein 1 (VDUP1) and IκBα protein levels. These data indicate that AS-IV may be effective in the protection of NEC-induced ileum degeneration by inhibiting the levels of inflammatory markers and oxidative stress via the regulation of the VDUP1/NF-κB signaling pathway.

Suppression of P2X7/NF-κB pathways by Schisandrin B contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury.

The aim of the present study was to assess the effects and mechanisms of Schisandrin B (SchB) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg), and SchB (25, 50, and 75 mg/kg) was injected 1 h before LPS challenge by gavage. After 12 h, bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected. Histological studies demonstrated that SchB attenuated LPS-induced interstitial edema, hemorrhage, and infiltration of neutrophils in the lung tissue. SchB pretreatment at doses of 25, 50, and 75 mg/kg was shown to reduce LPS-induced lung wet-to-dry weight ratio and lung myeloperoxidase activity. In addition, pretreatment with SchB lowered the number of inflammatory cells and pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in BALF. The mRNA and protein expression levels of nuclear factor kappa B (NF-κB) signaling-related molecules activated by P2X7 were investigated to determine the molecular mechanism of SchB. The findings presented here suggest that the protective mechanism of SchB may be attributed partly to the decreased production of pro-inflammatory cytokines through the inhibition of P2X7/NF-κB activation.

MiR-455 enhances adipogenic differentiation of 3T3-L1 cells through targeting uncoupling protein-1.

Accumulating evidence suggests that microRNAs (miRNAs) play an important role in regulating the pathways in adipose tissue that control processes such as adipogenesis, insulin resistance, and inflammation. Adipogenic differentiation of preadipocytes is a complex process regulated by various factors including miRNAs and cytokines. MiR-455 is a well-known miRNA that enhances adipogenesis. Uncoupling protein-1 (UCP-1), a heparinbinding growth factor, plays a negative role in adipogenesis. In this investigation, we demonstrate that UCP-1 is a target gene of miR-455 during adipogenic differentiation in 3T3-L1 preadipocytes. MiR-455 downregulates UCP-1 expression through interaction with a target site of miR-455 in the coding region of mouse UCP-1. The rare codons upstream of the target site regulate miR-455-induced translational knockdown of UCP-1, which provides more insight into the mechanism of adipogenic differentiation. Thus, these results suggest that the acceerative adipogenic effect of miR-455 in 3T3-L1 cells is due, at least in part, to suppression of UCP-1.