The mechanism of NRF2 regulating cell proliferation and mesenchymal transformation in pulmonary hypertension.

Pulmonary hypertension (PH) is a fatal disease with no existing curative drugs. NF-E2-related factor 2 (NRF2) a pivotal molecular in cellular protection, was investigated in PH models to elucidate its role in regulating abnormal phenotypes in pulmonary artery cells. We examined the expression of NRF2 in PH models and explored the role of NRF2 in regulating abnormal phenotypes in pulmonary artery cells. We determined the expression level of NRF2 in lung tissues of PH model decreased significantly. We found that NRF2 was reduced in rat pulmonary artery endothelial cells (rPAEC) under hypoxia, while it was overexpressed in rat pulmonary artery smooth muscle cells (rPASMC) under hypoxia. Next, the results showed that knockdown NRF2 in rPAEC promoted endothelial-mesenchymal transformation and upregulated reactive oxygen species level. After the rPASMC was treated with siRNA or activator, we found that NRF2 could accelerate cell migration by affecting MMP2/3/7, and promote cell proliferation by regulating PDGFR/ERK1/2 and mTOR/P70S6K pathways. Therefore, the study has shown that the clinical application of NRF2 activator in the treatment of pulmonary hypertension may cause side effects of promoting the proliferation and migration of rPASMC. Attention should be paid to the combination of NRF2 activators.

Natural compound Sanggenon C inhibits porcine reproductive and respiratory syndrome virus replication in piglets.

Porcine reproductive and respiratory syndrome virus is one of the main pathogens threatening the global pig industry, and there is still a lack of effective therapeutic drugs. Sanggenon C is a flavanone Diels-Alder adduct compound extracted from the root bark of the mulberry genus, which has blood pressure-reducing, anti-atherosclerotic, anti-oxidative, and anti-inflammatory effects. In our previous study, Sanggenon C was confirmed to significantly inhibit PRRSV replication in vitro. However, its antiviral potential to inhibit PRRSV infection in vivo has not been evaluated in piglets. Here, the antiviral effect of Sanggenon C was evaluated in PRRSV-challenged piglets based on assessments of rectal temperature, viral load, pathological changes of lung tissue and secretion of inflammatory cytokines. The results showed that Sanggenon C treatment relieved the clinical symptoms, reduced the viral loads in the lungs and bloods, alleviated the pathological damage of lung tissue, decreased the secretion of inflammatory cytokines, and shorten the excretion time of virus from the oral and nasal secretions and feces of piglets after PRRSV infection. The results indicated that Sanggenon C is a promising anti-PRRSV drug, which provides a new strategy for the prevention and control of PRRS in clinical practice.

Mice lacking 1,4,5-triphosphate inositol type III receptor demonstrate inhibition of hypoxic pulmonary hypertension.

Hypoxic pulmonary hypertension (HPH) is a respiratory disease characterized by increased pulmonary vascular resistance and pulmonary arterial pressure. Persistent hypoxia alters the metabolic and transport functions of endothelial cells and promotes thrombosis and inflammation. Type 3 inositol-1,4,5-trisphosphate receptor (IP3R3) controls the release of calcium ions from the endoplasmic reticulum to the cytoplasm and mitochondria and is involved in cell proliferation, migration, and protein synthesis. In this study, we investigated the role and function of IP3R3 in HPH. The results showed that the expression level of IP3R3 was increased in pulmonary artery endothelial cells (PAECs) in a rat HPH model. The pulmonary artery pressure indices of IP3R3(-/-) mice with persistent hypoxia were significantly lower than those of HPH mice. The expression level of IP3R3 was significantly increased in hypoxia-treated PAECs. Knockdown of IP3R3 significantly inhibited the proliferation, migration and mesenchymal transition of PAECs induced by hypoxia. In conclusion, knockdown of IP3R3 can inhibit hypoxia-induced dysfunctions in PAECs, thus enabling IP3R3(-/-) mice to avoid HPH development. IP3R3 plays a key role in HPH and can be used as a potential target for the prevention and treatment of HPH.

Reconfigurable Inverse Opal Structure Film for a Rewritable and Double-Sided Photonic Crystal Paper.

A rewritable photonic crystal (PC) paper as an environmentally friendly and low-resource-consuming material for information storage and spreading has gradually become a research hotspot. In this work, a novel rewritable PC paper with inkless writing and double-sided rewritability properties was developed. A double-sided epoxy resin PC paper exhibiting an inverse opal structure and a bright structural color was fabricated using the sacrificial template method. Carbon black was doped into the material to increase color saturation and purity while preventing light transmission and protecting the double-sided structural color from interference. The force of sliding friction and deformation triggered by capillary pressure as well as swelling-triggered recovery of the inverse opal structure led to an easy rewriting of the PC paper. The PC paper exhibited excellent rewritability even after 50 runs of the rewriting process. Given the inkless and double-sided rewriting, this study provides a new method for the preparation of rewritable PC papers.

Electrospray deposition of carbon nanotube thin films for flexible transparent electrodes.

Flexible transparent carbon nanotube (CNT) electrodes were fabricated by electrospray deposition, a large-area scalable and cost-effective process. The carbon nanotubes were dispersed in N,N-dimethylformamide (DMF) and deposited on polyethylene terephthalate (PET) substrates by electrospray deposition process at room temperature and atmospheric pressure. Major process variables were characterized and optimized for the electrospray process development such as electric field between nozzle and substrates, CNT solution flowrate, gap between nozzle and substrates, solution concentration, solvent properties and surface temperature. The sheet resistance of the electrospray deposited CNT films were reduced by HNO3 doping process. 169 Omega/sq sheet resistance and 86% optical transmittance was achieved with low surface roughness of 1.2 nm. The films showed high flexibility and transparency, making them potential replacements of ITO or ZnO in such as solid state lighting, touch panels, and solar cells. Electrospray process is a scalable process and we believe that this process can be applied for large area carbon nanotube film formation.

Bupivacaine versus normal saline for relief of post-adenotonsillectomy pain in children: a meta-analysis.

OBJECTIVE: A meta-analysis was performed to explore the role of peri-operative bupivacaine infiltration in the relief of pain in adenotonsillectomy. METHODS: Data from Medline, EMBase, Springer and the Cochrane Collaboration database were searched. Reference lists from identified publications were scanned. RevMan 5.0 software was used for statistical analysis. RESULTS: 7 random controlled tests (a total of 286 cases) were included. Pain intensity was evaluated by VAS score or Cheops score. The pain of group bupivacaine (Group B) was less severe than group placebo (Group P). Analgesic requirement of Group B was less than Group P. Nevertheless the difference of complication between bupivacaine and placebo had no statistical difference. CONCLUSION: Bupivacaine infiltration is a safe and effective method for relief of pediatric post-adenotonsillectomy pain.

[Effects of human urinary tissue kallikreins on vasodilation of basilar artery in rabbits with symptomatic cerebral vasospasm].

OBJECTIVE: To evaluate the effects of urinary kallidinogenase on subarachnoid hemorrhage (SAH) in rabbits. METHODS: Rabbits symptomatic cerebral vasospasm model was built though Endo method, among the 40 rabbits, 8 died or had severe nervous system syndrome, the other 32 were randomly divided into 4 groups:group A, control group, injection of normal saline to the cisterna magna;group B, subarachnoid hemorrhage;group C, injection of human urinary tissue kallikreins;group D, treated with Nimodipine. The behavior scores, neurological scores and cerebral angiography changes were observed. RESULTS: Food intake obviously decreased and neurological deficit were seen in group B, while which were attenuated in group C and group D, and group A was normal. Comparing the diameter of basilar artery was (1.9 +/- 0.3) mm before SAH, the diameter of group B 4 d later was (1.5 +/- 0.3) mm, 7 d later (1.4 +/- 0.3) mm, the difference was significant (P < 0.05). Comparing with group C on the day 4th and 7th, the diameters of basilar artery were significantly different (P < 0.001). Comparing with group D on the day 4th, 7th and 14th, there was no obvious improvement. CONCLUSION: Urinary kallidinogenase and Nimodipine can obviously alleviate symptomatic cerebral vasospasm in rabbits remarkably, but the former's effect of attenuating vasospasm is better than that of Nimodipine.

[Effect of transcutaneous acupoint electrical stimulation on lipid peroxidation and cognitive function in patients experiencing craniotomy].

OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) on serum superoxide dismutase (SOD) activity, malondialdehyde (MDA) and S100beta contents in craniotomy patients for studying its cerebral protection mechanism. METHODS: Fifty patients scheduled for neurosurgery were randomly divided into TAES group (n = 25) and control group (n=25) with randomized block method. For patients of TAES group, TAES was applied to bilateral Hegu (LI 4) and Quchi (LI 11), Zusanli (ST 36) and Sanyinjiao (SP 6) from 30 minutes on before anesthesia to the end of operation. Patients of control group were anesthetized with sevoflurane inhalation and intermittent (i.v.) of sulfenany and vecurnium bromide. Blood samples were taken for assaying serum SOD activity, MDA and S100beta contents with purinase oxydasis, biochemiluminescence and enzyme linked immunosorbent assay separately. Scores of cognitive ability were given by using Mini Mental State Examination (MMSE). RESULTS: In comparison with pre-anesthesia, serum SOD activity decreased significantly 1 h after craniotomy in control group, at the end of operation in both control and TAES groups (P<0.05, P<0.01), and increased markedly 48 h after operation in control group (P<0.05). Serum MDA in control group increased significantly 48 h after operation, while that in TAES group reduced apparently 24 h after operation (P<0.01). Serum S100beta content in TAES group decreased remarkably 48 h after operation (P<0.01). Serum SOD activity of TAES group was significantly higher than that of control group 24 h after operation (P<0.05). Compared with control group, serum MDA contents of 24 h and 48 h after operation and serum S100beta levels at 1 h after craniotomy and 48 h after operation were markedly lower in TAES group (P<0.01, P<0.05). No significant differences were found between two groups in the cognitive function scores (P>0.05). CONCLUSION: TAES can increase serum SOD activity and reduce MDA and S100beta levels in patients undergoing craniotomy, which may contribute to its effect in reducing lipid peroxidation induced cerebral injury. But its impact on the patient's cognitive function needs study further.