Synergistic stabilization of garlic essential oil nanoemulsions by carboxymethyl chitosan/Tween 80 and application for coating preservation of chilled fresh pork.

Garlic essential oil (GEO) is a potential natural antioxidant and antimicrobial agent for food preservation, but its intrinsic low water-solubility, high volatility and poor stability severely limit its application and promotion. In this work, we investigated the synergistic stabilization of the GEO-in-water nanoemulsion using carboxymethyl chitosan (CCS) and Tween 80 (TW 80). Additionally, the nanoemulsion was fabricated through high-pressure microfluidization and utilized for the coating-mediated preservation of chilled pork. The garlic essential oil nanoemulsion (GEON) with 3.0 % CCS and 3.0 % TW 80 exhibited more homogeneous droplet size (around 150 nm) and narrower size distribution, while maintained long-term stability with no significant change in size during 30 d storage. Compared with free GEO, the GEONs exhibited a higher scavenging capacity to DPPH and ABTS free radicals as well as higher inhibitory effects against Escherichia coli and Staphylococcus aureus, suggesting that the encapsulation of GEO in nanoemulsion considerably improved its antioxidant and antibacterial activities. Furthermore, the results of coating preservation experiments showed that the GEON coating effectively expanded the shelf-life of chilled fresh pork for approximately one week. Altogether, this study would guide the development of GEO-loaded nanoemulsions, and promote GEON as a promising alternative for coating preservation of chilled fresh meat.

Disruption of adipocyte HIF-1α improves atherosclerosis through the inhibition of ceramide generation.

Atherosclerosis is a chronic multifactorial cardiovascular disease. Western diets have been reported to affect atherosclerosis through regulating adipose function. In high cholesterol diet-fed ApoE -/- mice, adipocyte HIF-1α deficiency or direct inhibition of HIF-1α by the selective pharmacological HIF-1α inhibitor PX-478 alleviates high cholesterol diet-induced atherosclerosis by reducing adipose ceramide generation, which lowers cholesterol levels and reduces inflammatory responses, resulting in improved dyslipidemia and atherogenesis. Smpd3, the gene encoding neutral sphingomyelinase, is identified as a new target gene directly regulated by HIF-1α that is involved in ceramide generation. Injection of lentivirus-SMPD3 in epididymal adipose tissue reverses the decrease in ceramides in adipocytes and eliminates the improvements on atherosclerosis in the adipocyte HIF-1α-deficient mice. Therefore, HIF-1α inhibition may constitute a novel approach to slow atherosclerotic progression.

Miro2 Regulates Inter-Mitochondrial Communication in the Heart and Protects Against TAC-Induced Cardiac Dysfunction.

Rationale: The constrained mitochondria in cardiomyocytes communicate with each other, through mitochondrial kissing or nanotunneling, forming a dynamically continuous network to share content and transfer signals. However, the molecular mechanism of cardiac inter-mitochondrial communication is unclear. Objective: To determine the molecular mechanism underlying the robust inter-mitochondrial communication and its pathophysiological relevance in the heart. Methods and Results: By mitochondria-targeted expressing the photoactivatable green fluorescent protein, we revealed that most mitochondrial nanotubes bridge communicating mitochondrial pairs were associated with microtubules. Miro2 (mitochondrial Rho GTPase), the outer mitochondrial membrane protein which usually mediates mitochondrial transport within cells, accompanied with mitochondrial nanotubes along microtubules in adult cardiomyocytes. Adenovirus mediated expression of Miro2 in cardiomyocytes accelerated inter-mitochondrial communication through increasing mitochondrial nanotunneling and mitochondrial kissing between adjacent mitochondrial pairs. In transverse aortic constriction-induced hypertrophic mouse hearts Miro2 protein was declined, accompanied with decreased inter-mitochondrial communication. Miro2 transgenic mice showed ameliorated cardiac function, increased mitochondrial nanotube formation and inter-mitochondrial communication, and improved mitochondrial function after transverse aortic constriction. E3 ubiquitin ligase Parkin was increased in transverse aortic constriction mouse hearts and phenylephrine stimulation-induced hypertrophic cardiomyocytes. Inhibition of proteasome blocked phenylephrine-induced decrease of Miro2, and Parkin overexpression led to the decrease of Miro2. Conclusions: Mitochondrial Miro2 expression levels regulate inter-mitochondrial communication along microtubules in adult cardiomyocytes, and degradation of Miro2 through Parkin-mediated ubiquitination contributes to impaired inter-mitochondrial communication and cardiac dysfunction during hypertrophic heart diseases.Visual Overview: An online visual overview is available for this article.

Computational characterization and identification of human polycystic ovary syndrome genes.

Human polycystic ovary syndrome (PCOS) is a highly heritable disease regulated by genetic and environmental factors. Identifying PCOS genes is time consuming and costly in wet-lab. Developing an algorithm to predict PCOS candidates will be helpful. In this study, for the first time, we systematically analyzed properties of human PCOS genes. Compared with genes not yet known to be involved in PCOS regulation, known PCOS genes display distinguishing characteristics: (i) they tend to be located at network center; (ii) they tend to interact with each other; (iii) they tend to enrich in certain biological processes. Based on these features, we developed a machine-learning algorithm to predict new PCOS genes. 233 PCOS candidates were predicted with a posterior probability >0.9. Evidence supporting 7 of the top 10 predictions has been found.

Adipocyte-derived Lysophosphatidylcholine Activates Adipocyte and Adipose Tissue Macrophage Nod-Like Receptor Protein 3 Inflammasomes Mediating Homocysteine-Induced Insulin Resistance.

The adipose Nod-like receptor protein 3 (NLRP3) inflammasome senses danger-associated molecular patterns (DAMPs) and initiates insulin resistance, but the mechanisms of adipose inflammasome activation remains elusive. In this study, Homocysteine (Hcy) is revealed to be a DAMP that activates adipocyte NLRP3 inflammasomes, participating in insulin resistance. Hcy-induced activation of NLRP3 inflammasomes were observed in both adipocytes and adipose tissue macrophages (ATMs) and mediated insulin resistance. Lysophosphatidylcholine (lyso-PC) acted as a second signal activator, mediating Hcy-induced adipocyte NLRP3 inflammasome activation. Hcy elevated adipocyte lyso-PC generation in a hypoxia-inducible factor 1 (HIF1)-phospholipase A2 group 16 (PLA2G16) axis-dependent manner. Lyso-PC derived from the Hcy-induced adipocyte also activated ATM NLRP3 inflammasomes in a paracrine manner. This study demonstrated that Hcy activates adipose NLRP3 inflammasomes in an adipocyte lyso-PC-dependent manner and highlights the importance of the adipocyte NLRP3 inflammasome in insulin resistance.

Ethyl cellulose nanodispersions as stabilizers for oil in water Pickering emulsions.

Ethyl cellulose (EC) nanodispersions have been prepared through a facile procedure, a process involved the dissolution of EC into ethanol, followed by dipping it in Xanthan Gum (XG) solution (0.1%, used as anti-solvent), and then removed the ethanol. The influences of preparation conditions on the structure and properties of the EC nanodispersions were investigated. The prepared EC nanodispersion had a negative surface potential, which contributed to its stabilization. The particle size of the nanodispersions could be controlled by changing the concentration of EC. Furthermore, the EC nanodispersions had a potential application for the stabilization of oil/water Pickering emulsion. The obtained Pickering emulsions showed high stability.

Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma.

BACKGROUND: The involvement of lipid metabolism in tumourigenesis and the progression of clear cell renal cell carcinoma (ccRCC) have been reported. However, the role of phospholipid profile alterations in ccRCC has not yet been systematically explored. In the present study, we compared the phospholipid compositions between ccRCC and paired normal renal tissues. METHODS: The phospholipid compositions of paired ccRCC and normal renal tissues were evaluated using liquid chromatography tandem mass spectrometry (LC/MS/MS). To evaluate the mRNA and protein levels of lysophosphatidylcholine acyltransferase (LPCAT), which converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), qRT-PCR, western blotting and immunohistochemistry were performed. The correlations of LPCAT1 expression with clinicopathological features and prognosis were assessed. In addition, siRNAs were used to knockdown LPCAT1 expression in ccRCC cell lines, and its effect on cell proliferation, cell cycle, migration and invasion were investigated. RESULTS: The phospholipid compositions of ccRCC and normal renal tissues were significantly different. Multiple LPC species were decreased and corresponding PC species were increased in cancer tissues. The mRNA and protein levels of LPCAT1 were up-regulated in ccRCC tissues compared with normal renal tissues, and LPCAT1 expression was significantly correlated with unfavourable pathological features (higher tumour grade, higher TNM stage and larger tumour size) and overall survival. In cell line experiments, LPCAT1 knockdown depleted PCs, inhibited cell proliferation, migration and invasion and induced cell cycle arrest at the G0/G1 phase. CONCLUSION: Selective changes in PC and LPC composition were observed in ccRCC tissues. The overexpression of LPCAT1 promotes the development and progression of ccRCC, likely through the conversion of LPC to PC.

Homocysteine ameliorates the endothelium-independent hypoxic vasoconstriction via the suppression of phosphatidylinositol 3-kinase/Akt pathway in porcine coronary arteries.

OBJECTIVE: Endothelium-independent coronary vasoconstriction induced by continuous hypoxia contributes to the development of ischemic heart diseases. Acute elevation of homocysteine (Hcy) has a potent of vasodilation. The present study aims to investigate the role of Hcy in endothelium-independent hypoxic coronary vasoconstriction and its underlying mechanisms. METHODS AND RESULTS: Vessel tension of isolated porcine coronary arteries was measured by organ chamber study and the protein expression were detected by western blot. A sustained contraction of porcine coronary artery was induced when exposed to prolonged hypoxia for more than 15 min, which was significantly reduced by Hcy in a dose-dependent manner but not affected by cysteine or N-acetyl-l-cysteine. Phosphorylated myosin light chain (MLC-p) at Ser19 was decreased when exposure to hypoxia for 15 min, and could be reversed by prolonged hypoxia for 30 and 60 min. The recovery of MLC-p at Ser19 by hypoxia for more than 30 min could be abolished by Hcy. The protein levels of phosphorylated Akt at Ser473 and phosphorylated P85 at Tyr508 were decreased by Hcy in normoxia, and were also reduced exposure to hypoxia for 15 min and then augmented by prolonged hypoxia for more than 30 min, which could be prevented by Hcy. The protein level of P110α was not affected by Hcy or prolonged hypoxia. CONCLUSIONS: This study demonstrates that Hcy can ameliorate the endothelium-independent hypoxic coronary vasoconstriction, in which the inhibition of PI3K/Akt signaling pathway may be involved.

Induction of cell-cycle arrest by all-trans retinoic acid in mouse embryonic palatal mesenchymal (MEPM) cells.

all-trans retinoic acid (atRA), the oxidative metabolite of vitamin A, is essential for normal embryonic development. Also, high levels of atRA are teratogenic in many species and can effectively induce cleft palate in the mouse. Most cleft palate resulted from the failed fusion of secondary palate shelves, and maintenance of the normal cell proliferation is important in this process of shelf growth. To clarify the mechanism by which atRA causes cleft palate, we investigated the effect of atRA on proliferation activity and cell cycle distribution in mouse embryonic palatal mesenchymal (MEPM) cells. atRA inhibited the growth of MEPM cells by inducing apoptosis in a dose-dependent manner. atRA also caused a G1 block in the cell cycle with an increase in the proportion of cells in G0/G1 and a decrease in the proportion of cells in S phase, as determined by flow cytometry. We next investigated the effects of atRA on molecules that regulate the G1 to S phase transition. These studies demonstrated that atRA inhibited expression of cyclins D and E at the protein level. Furthermore, atRA treatment reduced phosphorylated Rb and decreased cdk2 and cdk4 kinase activity. These data suggest that atRA had antiproliferative activity by modulating G1/S cell cycle regulators and by inhibition of Rb phosphorylation in MEPM cells, which might account for the pathogenesis of cleft palate induced by retinoic acid.