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Background and purposeTetramethylpyrazine (TMP) was originally isolated from the traditional Chinese herb ligusticum and the fermented Japanese food natto and has since been synthesized. TMP has a long history of beneficial effects in the treatment of many cardiovascular diseases. Here we have evaluated the therapeutic effects of TMP on pulmonary hypertension (PH) in animal models and in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH).Experimental approachThree well-defined models of PH -chronic hypoxia (10% O2 )-induced PH (HPH), monocrotaline-induced PH (MCT-PH) and Sugen 5416/hypoxia-induced PH (SuHx-PH) - were used in Sprague-Dawley rats, and assessed by echocardiography, along with haemodynamic and histological techniques. Primary cultures of rat distal pulmonary arterial smooth muscle cells (PASMCs) were used to study intracellular calcium levels. Western blots and RT-qPCR assays were also used. In the clinical cohort, patients with PAH or CTEPH were recruited. The effects of TMP were evaluated in all systems.Key resultsTMP (100 mg·kg-1 ·day-1 ) prevented rats from developing experimental PH and ameliorated three models of established PH: HPH, MCT-PH and SuHx-PH. The therapeutic effects of TMP were accompanied by inhibition of intracellular calcium homeostasis in PASMCs. In a small cohort of patients with PAH or CTEPH, oral administration of TMP (100 mg, t.i.d. for 16 weeks) increased the 6-min walk distance and improved the 1-min heart rate recovery.Conclusion and implicationsOur results suggest that TMP is a novel and inexpensive medication for treatment of PH. Clinical trial is registered with www.chictr.org.cn (ChiCTR-IPR-14005379).

Photodynamic antimicrobial therapy via producing ROS based on light-responsive nanoparticles has attracted worldwide attention because of the high selectivity and low side effects. However, biofilms and bacterial membranes provide a natural barrier to prevent the penetration of ROS, which impairs the photodynamic antibacterial efficiency of nanoparticles. Photothermal therapy is an effective strategy against biofilms and bacterial membranes because high temperature can destroy the biofilm structure and enhance the membrane permeability. Herein, Bi2S3 nanorods were anchored on the surface of zinc-doped g-C3N4 (ZnCN) nanosheets to construct a ZnCN-Bi2S3 nanocomposite; then, it was incorporated into poly-l-lactic acid and prepared into scaffolds by the selective laser sintering technology. Bi2S3 nanorods not only endowed the scaffold with an excellent photothermal property but also strengthened the photodynamic effect of ZnCN nanosheets after forming the nanocomposite. The results showed that this nanocomposite had a lower recombination rate of photogenerated electron–hole pairs and produced higher photocurrent compared to those of the g-C3N4 nanosheets and Bi2S3 nanorods. The scaffold destroyed the biofilm and elevated the bacterial membrane permeability significantly and finally achieved 98.5% antibacterial rate for Staphylococcus aureus and 96.3% antibacterial rate for Pseudomonas aeruginosa. Encouragingly, the scaffold could also promote chondrogenic differentiation because of the continuous release of Zn ions. The scaffold containing ZnCN-Bi2S3 nanocomposites possessed excellent antimicrobial and cartilage regeneration functions, which displayed great potential in treating tracheal injuries. [ABSTRACT FROM AUTHOR]

Unlike the pulmonary artery (PA), the pathophysiological changes of the pulmonary vein (PV) in the development of pulmonary hypertension (PH) remain largely unknown. In this study, we comprehensively investigated the structural and functional changes in the PV isolated from the chronic hypoxia (CH; 10% O 2 , 21 days)-induced PH rat model (CHPH). Results showed that CH caused an increase in right ventricular pressure but did not affect the mean pulmonary venous pressure and the left atrial pressure. Similar to the PA, vascular lumen stenosis and medial thickening were also observed in the intrapulmonary veins isolated from the CHPH rats. Notably, CH induced more severe loss in the endothelium of intrapulmonary veins than the arteries. Then, the contractile response to 5-HT and U46619 was significantly greater in the intrapulmonary small veins (ISPV) and arteries (ISPA) isolated from CHPH rats than those from normoxic rats but not in the extrapulmonary and intrapulmonary large veins. Treatment with nifedipine (Nif), SKF96365 (SKF), or ryanodine and caffeine either partially attenuated (Nif) or dramatically abolished (SKF or ryanodine and caffeine) 5-HT-induced maximal contraction in ISPV from both normoxic and CHPH rats. Because of the severe loss of endothelium in the PV of CHPH rats, the decrease in acetylcholine (ACh)-induced endothelium-dependent relaxation was significantly larger in ISPV than ISPA, whereas the sodium nitroprusside-induced endothelium-independent relaxation was not altered in both ISPA and ISPV. In conclusion, our results provide fundamental data to comprehensively define the PV system in CHPH rat model.