Recent Advances on the Molecular Mechanism and Clinical Trials of Venous Thromboembolism.

Venous thromboembolism is a condition that includes deep vein thrombosis and pulmonary embolism. It is the third most common cardiovascular disease behind acute coronary heart disease and stroke. Over the past few years, growing research suggests that venous thrombosis is also related to the immune system and inflammatory factors have been confirmed to be involved in venous thrombosis. The role of inflammation and inflammation-related biomarkers in cerebrovascular thrombotic disease is the subject of ongoing debate. P-selectin leads to platelet-monocyte aggregation and stimulates vascular inflammation and thrombosis. The dysregulation of miRNAs has also been reported in venous thrombosis, suggesting the involvement of miRNAs in the progression of venous thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is a crucial component of the plasminogen-plasmin system, and elevated levels of PAI-1 in conjunction with advanced age are significant risk factors for thrombosis. In addition, it has been showed that one of the ways that neutrophils promote venous thrombosis is the formation of neutrophil extracellular traps (NETs). In recent years, the role of extracellular vesicles (EVs) in the occurrence and development of VTE has been continuously revealed. With the advancement of research technology, the complex regulatory role of EVs on the coagulation process has been gradually discovered. However, our understanding of the causes and consequences of these changes in venous thrombosis is still limited. Therefore, we review our current understanding the molecular mechanisms of venous thrombosis and the related clinical trials, which is crucial for the future treatment of venous thrombosis.

Polyphosphate kinase 1 is required for the pathogenesis process of meningitic Escherichia coli K1 (RS218).

AIM: Polyphosphate kinase 1 (PPK1), encoded by the ppk1 gene, is one of the major enzymes to reversibly catalyze the synthesis of polyphosphate (poly P) from the terminal phosphate of ATP. Poly P confers resistance to stress in a number of bacterial species but its role in the virulence of meningitic bacterial pathogens is unknown. The aim of this study was to determine the role of PPK1 in the pathogenesis of Escherichia coli meningitis. MATERIALS & METHODS: An isogenic in-frame ppk1 deletion mutant (PD44) of E. coli K1 strain E44 was constructed and characterized. Human brain microvascular endothelial cells and neonatal rats were used as the in vitro and in vivo models, respectively, to evaluate bacterial adhesion/invasion and the abilities of bacteria crossing the blood-brain barrier (BBB) to cause meningitis. The survival of PD44 and E44 under osmotic and acid stress conditions were also examined. RESULTS: Poly P levels in E44 were clearly higher than those in PD44, especially at the stationary phase (SP). The ppk1 deletion mutant PD44 also showed poor survival rates during osmotic shock and acidic challenge, which the bacteria would face during pathogenesis. In vitro and in vivo assays revealed that PD44 was defective in bacterial adhesion and translocation across the BBB. By using the Evans blue method, we found that E44-induced permeability of the BBB in neonatal rats was significantly higher than that of the animals infected with PD44. Cytokine ELISA results showed that the TNF-α and IL-1ß levels in the serum and brain tissues of the neonatal rats infected with PD44 were lower than that of the E44 group. A more obvious meningeal inflammation could be observed in the brain tissues of the rats infected with E44 when compared with that of the PD44 group by histopathological examination. Furthermore, the mRNA expression of IbeR, which is an RpoS-like regulator contributing to the SP regulation in E44, was found to be decreased in PD44 when compared with the parent strain. PD44 was also deficient in mRNA expression of the invasin IbeA, the adhesin FimH and the outer member protein A, which contributes to E44 penetration across BBB and resistance to the stimulations of low pH and high osmolarity. CONCLUSION: These results indicate that ppk1 plays an important role in stress adaption and virulence in meningitic E. coli K1 strain E44, and controls the relevant phenotypes by modulating the expression of the SP regulatory gene ibeR and the virulence genes ibeA, fimH and ompA.

Autologous nucleus pulposus transplantation to lumbar 5 dorsal root ganglion after epineurium dissection in rats: a modified model of non-compressive lumbar herniated intervertebral disc.

BACKGROUND: Nucleus pulposus of intervertebral discs has proinflammatory characteristics that play a key role in neuropathic pain in lumbar herniated intervertebral disc. One of the most commonly used animal models (the traditional model) of non-compressive lumbar herniated intervertebral disc is created by L4-L5 hemilaminectomy and the application of autologous nucleus pulposus to cover the left L4 and L5 nerve roots in rats. However, such procedures have the disadvantages of excessive trauma and low success rate. We proposed a modified model of non-compressive lumbar herniated intervertebral disc in which only the left L5 dorsal root ganglion is exposed and transplanted with autologous nucleus pulposus following incision of epineurium. We aimed to compare the modified model with the traditional one with regard to trauma and success rate. METHODS: Thirty Sprague-Dawley male rats were randomized into three groups: sham operation group (n = 6), traditional group (n = 12), and modified group (n = 12). The amount of blood loss and operative time for each group were analyzed. The paw withdrawal threshold of the left hind limb to mechanical stimuli and paw withdrawal latency to heat stimuli were examined from the day before surgery to day 35 after surgery. RESULTS: Compared with the traditional group, the modified group had shorter operative time, smaller amount of blood loss, and higher success rate (91.7% versus 58.3%, P < 0.05). There was no decrease in paw withdrawal latency in any group. The sham operation group had no decrease in postoperative paw withdrawal threshold, whereas the modified and traditional groups had significant reduction in paw withdrawal threshold after surgery (mechanical hyperalgesia). CONCLUSIONS: Transplantation of nucleus pulposus onto the L5 dorsal root ganglion following incision of epineurium in rats established an improved animal model of non-compressive lumbar herniated intervertebral disc with less trauma and more stable pain ethology.

[Studies on phloroglucinol derivatives of Dryopteris fragrans L].

OBJECTIVE: To study the phloroglucinol derivatives of Dryopteris fragrans. METHODS: Isolation and purification were carried out on repeated silica gel, Sephadex LH-20 column chromatography and prepare HPLC. The structures of the compounds were determined by physicochemical properties and spectral analysis. RESULTS: Four compounds were isolated and identified as aspidin PB (I), dryofragin (II), aspidinol (III), aspidin BB (IV). CONCLUSION: Compounds IV is isolated from this plant for the first time.

[Study on terpene of Dryopteris fragrans L].

OBJECTIVE: To study the terpene of Dryopteris fragrans. METHODS: Isolation and purification were carried out on repeated silica gel, Sephadex LH-20 column chromatography and prepare HPLC. The structures of the compounds were determined by physicochemical properties and spectral analysis. RESULTS: Four compounds were isolated and identified as 10-hydroxyl-15-oxo-alpha-cadinol (I), albicany acetate (II), alpha-cadinene (III), albicanol (IV). CONCLUSION: Compounds I is isolated from this plant for the first time.