缬沙坦对大鼠心室肌细胞L-型钙通道电流的影响

目的研究AT1受体拮抗剂缬沙坦对正常大鼠心室肌细胞L-钙电流(Ica-L)的影响。方法采用全细胞膜片钳技术,观察0.4μmol/L的缬沙坦引起单个大鼠心室肌细胞L型钙通道电流变化。结果0.4μmol/L缬沙坦使正常大鼠心室肌细胞L型钙电流峰值明显降低(P<0.01),I-V曲线上移,但不改变其激活电位、峰值电位和反转电位。不影响通道稳态激活曲线,使稳态失活曲线左移。结论0.4μmol/L缬沙坦可直接阻断大鼠心室肌细胞L型钙通道,改变心室肌细胞的电生理特性,可能是其抗心律失常的机制之一。     

Evaluation of physician experience in achieving non-perfused volume ratio of high-intensity focused ultrasound ablation for uterine fibroids: a multicentre study

ObjectiveTo evaluate the effect of different levels of physician experience on the high-intensity focused ultrasound (HIFU) ablation of uterine fibroids and to provide a reference for the use of non-perfused volume ratio (NPVR) standards during training.MethodsThis prospective multicentre study enrolled patients with uterine fibroids. The effect of the physician’s level of experience on the outcomes under different NPVR standards and the learning curve of six centres without HIFU experience were analysed. The impact of patient demographic and clinical characteristics were also evaluated.ResultsA total of 1352 patients from 20 centres were included in the study. The median NPVRs were 92.00%, 88.10% and 92.86% in the no experience group, inexperienced group and experienced group, respectively. Posterior wall fibroids, lateral wall fibroids and fundus fibroids were inversely correlated with NPVR, while experienced physicians were positively correlated with NPVR. With NPVR ≥ 70% and NPVR ≥ 80% standards, physicians in the no experience group completed the learning curve on the 11th and 16th procedure, respectively. Physicians under a standard of an NPVR ≥ 90% did not complete the learning curve.ConclusionsNPVR ≥ 80% is a standard that is worth using for HIFU treatment of uterine fibroids.     

Kinetic mechanism on elemental mercury adsorption by brominated petroleum coke in simulated flue gas

A waste byproduct of petroleum coke was obtained as a precursor modified with bromine for elemental mercury capture from simulated flue gas on a bench scale fixed-bed reactor. The reaction temperature, the initial inlet elemental mercury concentration and the individual flue gas components of O₂, NO, SO₂ and HCl were determined to explore their influence on elemental mercury capture by the brominated petroleum coke. Results indicate that high initial inlet mercury concentration can enhance initial mercury accumulation and the optimal temperature for elemental mercury capture by brominated petroleum coke is about 150 °C. Kinetic models reveal that the pseudo-second order and Elovich models are best fitted to the mercury adsorption process, indicating that chemisorption is the control step with the intra-particle diffusion and external mass transfer taking place simultaneously. The kinetic parameters demonstrate that the initial mercury adsorption rate (h or a) and the equilibrium adsorption quantity (Q_e) increase remarkably, when higher concentrations of O₂ or NO exist in N₂ atmosphere. On the contrary, Q_e decreases with the presence of high SO₂ or HCl, which indicates a two-sided effect on the performance of mercury adsorption owing to their concentrations.

A waste byproduct of petroleum coke was obtained as a precursor modified with bromine for elemental mercury capture from simulated flue gas on a bench scale fixed-bed reactor.     

The altering in sensory sensitivity: a current issue of female breast surgery

Breast surgery is an important treatment for women with malignant breast diseases. In addition to breast appearance, the integrity of breast function is increasing in patients with breast diseases. As the basis of breast physiological function, breast skin sensitivity is important to the quality of life of patients after surgery. Breast skin sensitivity gives the patient a “real” breast feeling. The sensory recovery after breast surgery has also become one of the important goals of breast surgery. In this review, we aim to discuss the research progress on recovery of breast skin sensitivity after different treatment modalities for breast disease.     

Vitamin D Enhances Neutrophil Generation and Function in Zebrafish (Danio rerio)

Vitamin D (VD) is a major regulator of calcium metabolism in many living organisms. In addition, VD plays a key role in regulating innate and adaptive immunity in vertebrates. Neutrophils constitute an important part of the first line of defense against invading microbes; however, the potential effect of VD on neutrophils remains elusive. Thus, in this study zebrafish in different developmental stages were utilized to identify the potential role of VD in the basal homeostasis and functions of neutrophils. Our results showed that addition of exogenous VD₃ promoted granulopoiesis in zebrafish larvae. Reciprocally, neutrophil abundance in the intestine of adult zebrafish with a cyp2r1 mutant, lacking the capacity to 25-hydroxylate VD, was reduced. Moreover, VD-mediated granulopoiesis was still observed in gnotobiotic zebrafish larvae, indicating that VD regulates neutrophil generation independent of the microbiota during early development. In contrast, VD was incapable to influence granulopoiesis in adult zebrafish when the commensal bacteria were depleted by antibiotic treatment, suggesting that VD might modulate neutrophil activity via different mechanisms depending on the developmental stage. In addition, we found that VD₃ augmented the expression of il-8 and neutrophil recruitment to the site of caudal fin amputation. Finally, VD₃ treatment significantly decreased bacterial counts and mortality in zebrafish infected with Edwardsiella tarda (E. tarda) in a neutrophil-dependent manner. Combined, these findings demonstrate that VD regulates granulopoiesis and neutrophil function in zebrafish immunity.     

Proteomic analysis of the effects of caffeine in a neonatal rat model of hypoxic‐ischemic white matter damage

AimWhite matter damage (WMD) is the main cause of cerebral palsy and cognitive impairment in premature infants. Although caffeine has been shown to possess neuroprotective effects in neonatal rats with hypoxic‐ischemic WMD, the mechanisms underlying these protective effects are unclear. Herein, proteins modulated by caffeine in neonatal rats with hypoxic‐ischemic WMD were evaluated.MethodsWe identified differential proteins and performed functional enrichment analyses between the Sham, hypoxic‐ischemic WMD (HI), and HI+caffeine‐treated WMD (Caffeine) groups. Confirmed the changes and effect of proteins in animal models and determined cognitive impairment via water maze experiments.ResultsIn paraventricular tissue, 47 differential proteins were identified between the Sham, HI, and Caffeine groups. Functional enrichment analyses showed that these proteins were related to myelination and axon formation. In particular, the myelin basic protein (MBP), proteolipid protein, myelin‐associated glycoprotein precursor, and sirtiun 2 (SIRT2) levels were reduced in the hypoxic‐ischemic WMD group, and this effect could be prevented by caffeine. Caffeine alleviated the hypoxic‐ischemic WMD‐induced cognitive impairment and improved MBP, synaptophysin, and postsynaptic density protein 95 protein levels after hypoxic‐ischemic WMD by preventing the HI‐induced downregulation of SIRT2; these effects were subsequently attenuated by the SIRT2 inhibitor AK‐7.ConclusionCaffeine may have clinical applications in the management of prophylactic hypoxic‐ischemic WMD; its effects may be mediated by proteins related to myelin development and synapse formation through SIRT2.     

A Novel Herbal Extract Blend Product Prevents Particulate Matters-Induced Inflammation by Improving Gut Microbiota and Maintaining the Integrity of the Intestinal Barrier

Air pollutants of PM2.5 can alter the composition of gut microbiota and lead to inflammation in the lung and gastrointestinal tract. The aim of this study was to evaluate the protective effect of a novel herbal extract blend, FC, composed of Lonicera japonica extract, Momordica grosvenori extract, and broccoli seed extract, on PM2.5-induced inflammation in the respiratory and intestinal tract. A549 cells and THP-1 cells, as well as C57BL/6 mice, were stimulated with PM2.5 to establish in vitro and in vivo exposure models. The models were treated with or without FC. The expression of inflammatory cytokines and tight junction proteins were studied. Proteomic analysis was performed to elucidate mechanisms. Mouse feces were collected for gut microbiota analysis. FC was shown to modulate the upregulation of pro-inflammatory cytokines mRNA expression in A549 and THP-1 cells and downregulated tight junction proteins mRNA expression in A549 cells due to PM2.5 stimulation. In animal models, the decreased expression of the anti-inflammatory factor il-10, tight junction protein ZO-1, and the elevated expression of COX-2 induced by PM2.5 were improved by FC intervention, which may be associated with zo-1 and cox-2 signaling pathways. In addition, FC was shown to improve the gut microbiota by increasing the abundance of beneficial bacteria.     

PRRSV Induces HMGB1 Phosphorylation at Threonine-51 Residue to Enhance Its Secretion

Porcine reproductive and respiratory syndrome virus (PRRSV) induces secretion of high mobility group box 1 (HMGB1) to mediate inflammatory response that is involved in the pulmonary injury of infected pigs. Our previous study indicates that protein kinase C-delta (PKC-delta) is essential for HMGB1 secretion in PRRSV-infected cells. However, the underlying mechanism in HMGB1 secretion induced by PRRSV infection is still unclear. Here, we discovered that the phosphorylation level of HMGB1 in threonine residues increased in PRRSV-infected cells. A site-directed mutagenesis study showed that HMGB1 phosphorylation at threonine-51 was associated with HMGB1 secretion induced by PRRSV infection. Co-immunoprecipitation (co-IP) of HMGB1 failed to precipitate PKC-delta, but interestingly, mass spectrometry analysis of the HMGB1 co-IP product showed that PRRSV infection enhanced HMGB1 binding to ribosomal protein S3 (RPS3), which has various extra-ribosomal functions. The silencing of RPS3 by siRNA blocked HMGB1 secretion induced by PRRSV infection. Moreover, the phosphorylation of HMGB1 at threonine-51 was correlated with the interaction between HMGB1 and RPS3. In vivo, PRRSV infection also increased RPS3 levels and nuclear accumulation in pulmonary alveolar macrophages. These results demonstrate that PRRSV may induce HMGB1 phosphorylation at threonine-51 and increase its interaction with RPS3 to enhance HMGB1 secretion. This finding provides insights into the pathogenesis of PRRSV infection.     

Identification of Inhibitors and Drug Targets for Human Adenovirus Infections

Adenoviruses can cause infections in people of all ages at all seasons of the year. Adenovirus infections cause mild to severe illnesses. Children, immunocompromised patients, or those with existing respiratory or cardiac disease are at higher risk. Unfortunately, there are no commercial drugs or vaccines available on the market for adenovirus infections. Therefore, there is an urgent need to discover new antiviral drugs or drug targets for adenovirus infections. To identify potential antiviral agents for adenovirus infections, we screened a drug library containing 2138 compounds, most of which are drugs with known targets and past phase I clinical trials. On a cell-based assay, we identified 131 hits that inhibit adenoviruses type 3 and 5. A secondary screen confirmed the antiviral effects of 59 inhibitors that inhibit the replication of adenoviruses type 3 or 5. Most of the inhibitors target heat shock protein, protein tyrosine kinase, the mTOR signaling pathway, and other host factors, suggesting that these host factors may be essential for replicating adenoviruses. Through this study, the newly identified adenovirus inhibitors may provide a start point for developing new antiviral drugs to treat adenovirus infections. Further validation of the identified drug targets can help the development of new therapeutics against adenovirus infections.