MicroRNA410 Inhibits Pulmonary Vascular Remodeling via Regulation of Nicotinamide Phosphoribosyltransferase

Nicotinamide phosphoribosyltransferase (NAMPT) upregulation in human pulmonary artery endothelial cells (hPAECs) is associated with pulmonary arterial hypertension (PAH) progression and pulmonary vascular remodeling. The underlying mechanisms regulating NAMPT expression are still not clear. In this study, we aimed to study the regulation of NAMPT expression by microRNA410 (miR410) in hPAECs and explore the role of miR410 in the pathogenesis of experimental pulmonary hypertension. We show that miR410 targets the 3' UTR of NAMPT and that, concomitant with NAMPT upregulation, miR410 is downregulated in lungs of mice exposed to hypoxia-induced pulmonary hypertension (HPH). Our results also demonstrate that miR410 directly inhibits NAMPT expression. Overexpression of miR410 in hPAECs inhibits basal and VEGF-induced proliferation, migration and promotes apoptosis of hPAECs, while miR410 inhibition via antagomirs has the opposite effect. Finally, administration of miR410 mimics in vivo attenuated induction of NAMPT in PAECs and prevented the development of HPH in mice. Our results highlight the role of miR410 in the regulation of NAMPT expression in hPAECs and show that miR410 plays a potential role in PAH pathobiology by targeting a modulator of pulmonary vascular remodeling

Identification of rat lung – prominent genes by a parallel DNA microarray hybridization

BACKGROUND: The comparison of organ transcriptomes is an important strategy for understanding gene functions. In the present study, we attempted to identify lung-prominent genes by comparing the normal transcriptomes of rat lung, heart, kidney, liver, spleen, and brain. To increase the efficiency and reproducibility, we first developed a novel parallel hybridization system, in which 6 samples could be hybridized onto a single slide at the same time. RESULTS: We identified the genes prominently expressed in the lung (147) or co-expressed in lung-heart (23), lung-liver (37), lung-spleen (203), and lung-kidney (98). The known functions of the lung-prominent genes mainly fell into 5 categories: ligand binding, signal transducer, cell communication, development, and metabolism. Real-time PCR confirmed 13 lung-prominent genes, including 5 genes that have not been investigated in the lung, vitamin D-dependent calcium binding protein (Calb3), mitogen activated protein kinase 13 (Mapk13), solute carrier family 29 transporters, member 1 (Slc29a1), corticotropin releasing hormone receptor (Crhr1), and lipocalin 2 (Lcn2). CONCLUSION: The lung-prominent genes identified in this study may provide an important clue for further investigation of pulmonary functions

Micro-RNA-1 is decreased by hypoxia and contributes to the development of pulmonary vascular remodeling via regulation of sphingosine kinase 1

Sphingosine kinase 1 (SphK1) upregulation is associated with pathologic pulmonary vascular remodeling in pulmonary arterial hypertension (PAH), but the mechanisms controlling its expression are undefined. In this study, we sought to characterize the regulation of SphK1 expression by micro-RNAs (miRs). In silico analysis of the SphK1 3'-untranslated region identified several putative miR binding sites, with miR-1-3p (miR-1) being the most highly predicted target. Therefore we further investigated the role of miR-1 in modulating SphK1 expression and characterized its effects on the phenotype of pulmonary artery smooth muscle cells (PASMCs) and the development of experimental pulmonary hypertension in vivo. Our results demonstrate that miR-1 is downregulated by hypoxia in PASMCs and can directly inhibit SphK1 expression. Overexpression of miR-1 in human PASMCs inhibits basal and hypoxia-induced proliferation and migration. Human PASMCs isolated from PAH patients exhibit reduced miR-1 expression. We also demonstrate that miR-1 is downregulated in mouse lung tissues during experimental hypoxia-mediated pulmonary hypertension (HPH), consistent with upregulation of SphK1. Furthermore, administration of miR-1 mimics in vivo prevented the development of HPH in mice and attenuated induction of SphK1 in PASMCs. These data reveal the importance of miR-1 in regulating SphK1 expression during hypoxia in PASMCs. A pivotal role is played by miR-1 in pulmonary vascular remodeling, including PASMC proliferation and migration, and its overexpression protects from the development of HPH in vivo. These studies improve our understanding of the molecular mechanisms underlying the pathogenesis of pulmonary hypertension

The Effect of Batter Characteristics on Protein-Aided Control of Fat Absorption in Deep-Fried Breaded Fish Nuggets

Soy protein (SP), egg white protein (EP), and whey protein (WP) at 6% w/w were individually incorporated into the batter of a wheat starch (WS) and wheat gluten (WG) blend (11:1 w/w ratio). Moisture adsorption isotherms of WS and proteins and the viscosity, rheological behavior, and calorimetric properties of the batters were measured. Batter-breaded fish nuggets (BBFNs) were fried at 170 °C for 40 s followed by 190 °C for 30 s, and pick-up of BBFNs, thermogravimetric properties of crust, and fat absorption were determined. The moisture absorption capacity was the greatest for WS, followed by WG, SP, EP, and WP. The addition of SP significantly increased the viscosity and shear moduli (G″, G′) of batter and pick-up of BBFNs, while EP and WP exerted the opposite effect (p \u3c 0.05). SP, EP, and WP raised WS gelatinization and protein denaturation temperatures and crust thermogravimetry temperature, but decreased enthalpy change (ΔH) and oily characteristics of fried BBFNs. These results indicate that hydrophilicity and hydration activity of the added proteins and their interactions with batter matrix starch and gluten reinforced the batter and the thermal stability of crust, thereby inhibiting fat absorption of the BBFNs during deep-fat frying

Effects of Freezing Methods on Lipid Oxidation and Microstructure of Muscle Fibers in Acipenser sinensis

This study was executed in order to investigate quality deterioration caused by lipid oxidation during the frozen storage of Acipenser sinensis. Fish pieces were stored at −18 ℃ for 24 weeks after being frozen using a freezer (−20 or −50 ℃) or liquid nitrogen (−80 or −110 ℃). The central temperature, fat and free fatty acid (FFA) contents, fatty acid composition, peroxide value (POV), thiobarbituric reactive substance (TBARS) value, and fluorescent compound content were measured and the microstructure of muscle fibers was also observed during the storage period for the purpose of evaluating the influence of freezing methods on lipid oxidation and muscle microstructure in Acipenser sinensis during frozen storage. The results showed that with increasing storage time, the fat and polyunsaturated fatty acid (PUFA) contents of the four fish samples decreased, while POV, TBARS value, and the contents of FFAs, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and fluorescent compounds increased. The gap between muscle fibers increased, which was accompanied by breaking of myofibrils. In addition, the contents of fat and PUFAs in liquid nitrogen frozen samples were significantly higher than those in freezer frozen ones (at the end of storage, the freezer frozen sample frozen at −20 ℃ contained 7.89% of fat compared to 9.13% for the liquid nitrogen frozen one at −80 ℃), while POV, TBARS value, and the contents of FFAs, SFAs, MUFAs and fluorescent compounds were significantly lower than those in freezer frozen samples (P < 0.05), and the muscle fiber structure was more complete. The above results indicated that liquid nitrogen frozen alleviated the degree of myofibrillar damage and lipid hydrolysis in Acipenser sinensis during frozen storage, thereby reducing the speed of lipid oxidation

Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling: A Mouse MRSA Pneumonia Model

Background: Linezolid (LZD) is beneficial to patients with MRSA pneumonia, but whether and how LZD influences global host lung immune responses at the mRNA level during MRSA-mediated pneumonia is still unknown.Methods: A lethal mouse model of MRSA pneumonia mediated by USA300 was employed to study the influence of LZD on survival, while the sublethal mouse model was used to examine the effect of LZD on bacterial clearance and lung gene expression during MRSA pneumonia. LZD (100mg/kg/day, IP) was given to C57Bl6 mice for three days. On Day 1 and Day 3 post infection, bronchoalveolar lavage fluid (BALF) protein concentration and levels of cytokines including IL6, TNFα, IL1β, Interferon-γ and IL17 were measured. In the sublethal model, left lungs were used to determine bacterial clearance and right lungs for whole-genome transcriptional profiling of lung immune responses.Results: LZD therapy significantly improved survival and bacterial clearance. It also significantly decreased BALF protein concentration and levels of cytokines including IL6, IL1β, Interferon-γ and IL17. No significant gene expression changes in the mouse lungs were associated with LZD therapy.Conclusion: LZD is beneficial to MRSA pneumonia, but it does not modulate host lung immune responses at the transcriptional level.</p

Effect of Dietary Fiber on Batter Characteristics and Oil Penetration in Deep-Fried Battered and Breaded Fish Nuggets from Silver Carp Surimi

To investigate the effect of dietary fiber on batter characteristics and oil penetration in deep-fried battered and breaded fish nuggets (BBFNs) from silver carp surimi, deep-fried BBFNs were prepared with model batters (composed of wheat starch and gluten) added with 8% apple fiber, 6% soybean fiber or 12% wheat bran fiber. The moisture adsorption isotherms of dietary fiber, wheat starch and gluten, and the pick-up of BBFNs were evaluated, the viscosity, rheological behavior and calorimetric properties of batters were measured, and the thermogravimetric properties of the crust, the water state and oil penetration of deep-fried BBFNs were also evaluated. The results showed that the moisture absorption capacity of wheat starch was the largest, followed by soybean fiber, apple fiber, wheat bran fiber, and gluten. Compared to that the control group (without dietary fiber), the addition of 8% apple fiber, 6% soybean fiber or 12% wheat bran fiber significantly increased the viscosity of batters and the pick-up of BBFNs (P < 0.05). The loss modulus (G’) and storage modulus (G”) of batters were decreased firstly, then increased rapidly and ultimately remained stable with an increase in oil temperature, and soybean fiber resulted in the highest G’ and G”, which contributed to the fastest formation of gels and the highest thermal stability of the crust after frying. The addition of each of the dietary fibers resulted in transformation of free water into bound water and increased the total moisture content of the crust. Soybean fiber resulted in the lowest oil penetration in deep-fried BBFNs, followed by apple fiber, wheat bran fiber and the control group. This study indicated that the addition of the three dietary fibers in model batter systems can accelerate the formation of gels, significantly improve the strength of the gels formed, and ultimately inhibit oil penetration in deep-fried BBFNs

A Rapid Detection Method for Freshness of Frozen Crayfish Based on Near-Infrared Spectroscopy

To establish a model based on near-infrared (NIR) spectra for quickly detecting the freshness of frozen crayfish, NIR spectra of thawed crayfish (tail, meat, and mince) were collected, and data were pretreated by first derivative, multiple scattering correction, wavelet transform (WT), or standard normal transform. The original and pretreated spectral data were correlated to total volatile basic nitrogen (TVB-N) contents using partial least squares (PLS) or convolutional neural network (CNN), and different quantitative prediction models were established and compared. The best model was selected to investigate its accuracy and applicability. The results showed that pretreatment methods had a significant influence on the accuracy of the model, and the CNN model established after spectral preprocessing had a better ability to predict the TVB-N content of crayfish compared with the PLS model. The CNN model based on the WT pretreated spectra of crayfish meat had the highest prediction accuracy for the validation set with correlation coefficients of 0.97 and 0.96, and root mean square errors of 1.26 and 0.93 mg/100 g for the calibration set and validation set, respectively. Moreover, the accuracy, precision, and sensitivity of the NIR method were within reasonable limits, and it had good figures of merit. According to the requirements of fast operation, accurate results, and low damage in practice, the WT-CNN-crayfish meat model was determined as the optimal model for predicting the TVB-N content in frozen crayfish. These results suggested that the WT-CNN-crayfish meat model have a great potential for predicting the TVB-N content and rapidly evaluating the freshness of frozen crayfish

Pathogenic Role of mTORC1 and mTORC2 in Pulmonary Hypertension.

Concentric lung vascular wall thickening due to enhanced proliferation of pulmonary arterial smooth muscle cells is an important pathological cause for the elevated pulmonary vascular resistance reported in patients with pulmonary arterial hypertension. We identified a differential role of mammalian target of rapamycin (mTOR) complex 1 and complex 2, two functionally distinct mTOR complexes, in the development of pulmonary hypertension (PH). Inhibition of mTOR complex 1 attenuated the development of PH; however, inhibition of mTOR complex 2 caused spontaneous PH, potentially due to up-regulation of platelet-derived growth factor receptors in pulmonary arterial smooth muscle cells, and compromised the therapeutic effect of the mTOR inhibitors on PH. In addition, we describe a promising therapeutic strategy using combination treatment with the mTOR inhibitors and the platelet-derived growth factor receptor inhibitors on PH and right ventricular hypertrophy. The data from this study provide an important mechanism-based perspective for developing novel therapies for patients with pulmonary arterial hypertension and right heart failure