Ameliorative effect of silymarin on the quality of frozen-thawed boar spermatozoa.

Although Silymarin (SMN) has powerful antioxidant properties, little is known about its effects on the quality of frozen-thawed boar sperm. The present study aimed to evaluate the influences of SMN added to the thawing extender on boar sperm parameters essential for fertilization. The frozen-thawed semen was diluted in a Modena thawing extender supplemented with different concentrations of SMN (0, 5, 10, 20 and 50 µM respectively), and then the changes in quality parameters, antioxidant capacity, mitochondrial function and in vitro fertilization (IVF) capability of frozen-thawed sperm were assessed. Here we demonstrated that the motility, plasma membrane integrity and acrosomal integrity of frozen-thawed sperm improved efficiently by SMN (p < .05). In antioxidant parameters evaluation, the tROS level and MDA content of frozen-thawed spermatozoa were reduced in the 20 µM SMN group, while the T-AOC activity significantly increased (p < .05), indicating that the supplementation with SMN can promote the antioxidant capacity of frozen-thawed boar sperm. Besides, we also discovered that the addition of SMN significantly upregulated ATP content and enhanced the mitochondrial activity of sperm. More interestingly, SMN promoted the activities of mitochondrial respiratory chain complexes (MRCC) I, II, III and IV in frozen-thawed sperm significantly. Functionally, the higher penetration rate and increased total efficiency of fertilization were observed in the 20 µM SMN group. In summary, supplementation with SMN in the thawing medium ameliorates the quality of frozen-thawed boar sperm by enhancing mitochondrial respiratory capacity, producing large amounts of ATP and regulating ROS formation.

Ripening induced degradation of pectin and cellulose affects the far infrared drying kinetics of mangoes.

The quality parameters of mangoes change during ripening, which has a vital impact on processing characteristics. Effects of ripening stage (four stages from the lowest to highest degree-RS-1, RS-2, RS-3, RS-4) on cell wall polysaccharides and far infrared drying kinetics of mangoes were investigated. As ripening progressed, the water-soluble pectin contents increased by 213.5%; while the chelate-, sodium carbonate-soluble pectin and hemicellulose contents decreased by 44.0%, 59.5% and 65.8%, respectively. Moreover, the molecular weight reduction confirmed the degradation of pectin. These further caused the alteration of cell wall structure and changes in water distribution. Meanwhile, the drying time of mangos with different ripeness were in the order: RS-3 > RS-4 > RS-2 > RS-1. It correlated with the degradation of cell wall polysaccharides, the destruction of cell wall and the increases in free water during ripening. The ripeness classification could effectively improve the uniformity and efficiency of fruits drying processing.

Drug repositioning based on network-specific core genes identifies potential drugs for the treatment of autism spectrum disorder in children.

Identification of exact causative genes is important for in silico drug repositioning based on drug-gene-disease relationships. However, the complex polygenic etiology of the autism spectrum disorder (ASD) is a challenge in the identification of etiological genes. The network-based core gene identification method can effectively use the interactions between genes and accurately identify the pathogenic genes of ASD. We developed a novel network-based drug repositioning framework that contains three steps: network-specific core gene (NCG) identification, potential therapeutic drug repositioning, and candidate drug validation. First, through the analysis of transcriptome data for 178 brain tissues, gene network analysis identified 365 NCGs in 18 coexpression modules that were significantly correlated with ASD. Second, we evaluated two proposed drug repositioning methods. In one novel approach (dtGSEA), we used the NCGs to probe drug-gene interaction data and identified 35 candidate drugs. In another approach, we compared NCG expression patterns with drug-induced transcriptome data from the Connectivity Map database and found 46 candidate drugs. Third, we validated the candidate drugs using an in-house mental diseases and compounds knowledge graph (MCKG) that contained 7509 compounds, 505 mental diseases, and 123,890 edges. We found a total of 42 candidate drugs that were associated with mental illness, among which 10 drugs (baclofen, sulpiride, estradiol, entinostat, everolimus, fluvoxamine, curcumin, calcitriol, metronidazole, and zinc) were postulated to be associated with ASD. This study proposes a powerful network-based drug repositioning framework and also provides candidate drugs as well as potential drug targets for the subsequent development of ASD therapeutic drugs.

Post-treatment with yiqifumai injection and its main ingredients attenuates lipopolysaccharide-induced microvascular disturbance in mesentery and ileum.

OBJECTIVE: To investigate the effect of Yiqifumai injection (YQFM), a compound Chinese medicine, and its main active ingredients on lipopolysaccharide (LPS)-induced microvascular disturbance in mesentery and ileum. METHODS: Rats were infused with LPS (5 mg/kg/h) for 90 min. Thirty minutes after initiation of LPS administration, YQFM (160 mg/kg/h), Rb1 (5 mg/kg/h), Sch (2.5 mg/kg/h), or Rb1+Sch (5 mg/kg/h + 2.5 mg/kg/h) was infused until 90 min. Human umbilical vein endothelial cells (HUVECs) were incubated with LPS (100 ng/ml) for 90 min. YQFM (1 mg/ml), Rb1 (100 µM), Sch (100 µM), or Rb1+Sch (200 µM) was added 30 min after initiation of LPS stimulation. RESULTS: Yiqifumai injection and Rb1+Sch inhibited mesenteric venule hyperpermeability, suppressed microvillar erosion and submucosal edema, and protected claudin-5 from downregulation and interleukin-1ß from upregulation in ileal tissues after LPS. Study in HUVECs confirmed the effect of YQFM and Rb1+Sch on JAM-1 after LPS and revealed a similar effect on other junction proteins. Moreover, YQFM and Rb1+Sch attenuated the dysfunctional energy metabolism and the activation of TLR-4/Src/NF-κB signaling with Rb1 and Sch being partially effective. CONCLUSION: These results demonstrated the beneficial effect of post-treatment with YQFM, which is attributable to its main ingredient Rb1 and Sch, and likely mediated by targeting TLR-4/Src/NF-κB signaling pathway.

Mannan-Binding Lectin Attenuates Inflammatory Arthritis Through the Suppression of Osteoclastogenesis.

Mannan-binding lectin (MBL) is a vital element in the host innate immune system, which is primarily produced by the liver and secreted into the circulation. Low serum level of MBL is reported to be associated with an increased risk of arthritis. However, the underlying mechanism by which MBL contributes to the pathogenesis of arthritis is poorly understood. In this study, we investigated the precise role of MBL on the course of experimental murine adjuvant-induced arthritis (AIA). MBL-deficient (MBL-/-) AIA mice showed significantly increased inflammatory responses compared with wild-type C57BL/6 AIA mice, including exacerbated cartilage damage, enhanced histopathological features and high level of tartrate-resistant acid phosphatase (TRAP)-positive cells. MBL protein markedly inhibited the osteoclast formation from human blood monocytes induced by receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in vitro. Mechanistic studies established that MBL inhibited osteoclast differentiation via down-regulation of p38 signaling pathway and subsequent nuclear translocation of c-fos as well as activation of nuclear factor of activated T-cells c1 (NFATc1) pathway. Importantly, we have provided the evidence that concentrations of MBL correlated negatively with the serum levels of amino-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (ß-CTX), serum markers of bone turnover, in patients with arthritis. Our study revealed an unexpected function of MBL in osteoclastogenesis, thus providing new insight into inflammatory arthritis and other bone-related diseases in patients with MBL deficiency.

Yiqifumai injection and its main ingredients attenuate lipopolysaccharide-induced cerebrovascular hyperpermeability through a multi-pathway mode.

OBJECTIVE: Yiqifumai injection is a compound Chinese medicine used to treat microcirculatory disturbance-related diseases clinically. Our previous study proved that Yiqifumai injection pretreatment inhibited lipopolysaccharide-induced venular albumin leakage in rat mesentery. This study aimed to investigate whether Yiqifumai injection attenuated cerebral microvascular hyperpermeability and corresponding contribution of its main ingredients. METHODS: Rats were challenged by lipopolysaccharide infusion (5 mg/kg/h) for 90 minutes. Yiqifumai injection (160 mg/kg/h), Rb1 (5 mg/kg/h), Sch (2.5 mg/kg/h), and Rb1 (5 mg/kg/h) + Sch (2.5 mg/kg/h) were infused 30 minutes before (pretreatment) or after (post-treatment) lipopolysaccharide administration. RESULTS: Both pretreatment and post-treatment with Yiqifumai injection attenuated cerebral venular albumin leakage during lipopolysaccharide infusion and cerebrovascular hyperpermeability at 72 hours after lipopolysaccharide infusion. Yiqifumai injection restrained the decreased junction protein expression, adenosine triphosphate content, and mitochondria complex I, II, IV, and V activities. Moreover, Yiqifumai injection inhibited toll-like receptor-4 expression, Src phosphorylation, and caveolin-1 expression. Its main ingredients Rb1 and Sch alone worked differently, with Rb1 being more effective for enhancing energy metabolism, while Sch attenuating toll-like receptor-4 expression and Src activation. CONCLUSION: Yiqifumai injection exerts a protective and ameliorated effect on cerebral microvascular hyperpermeability, which is more effective than any of its ingredients, possibly due to the interaction of its main ingredients through a multi-pathway mode.