Sphingomyelin synthase overexpression increases cholesterol accumulation and decreases cholesterol secretion in liver cells

<p>Abstract</p> <p>Background</p> <p>Studies have shown that plasma high density lipoprotein cholesterol levels are negatively correlated with the development of atherosclerosis, whereas epidemiological studies have also shown that plasma sphingomyelin level is an independent risk factor for atherosclerosis.</p> <p>Methods</p> <p>To evaluate the relationship between cellular sphingomyelin level and cholesterol metabolism, we created two cell lines that overexpressed sphingomyelin synthase 1 or 2 (SMS1 or SMS2), using the Tet-off expression system.</p> <p>Results</p> <p>We found that SMS1 or SMS2 overexpression in Huh7 cells, a human hepatoma cell line, significantly increased the levels of intracellular sphingomyelin, cholesterol, and apolipoprotein A-I and decreased levels of apolipoprotein A-I and cholesterol in the cell culture medium, implying a defect in both processes.</p> <p>Conclusions</p> <p>Our findings indicate that the manipulation of sphingomyelin synthase activity could influence the metabolism of sphingomyelin, cholesterol and apolipoprotein A-I.</p

Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice

<p>Abstract</p> <p>Background</p> <p>Sphingomyelin synthase 2 (SMS2) contributes to de novo sphingomyelin (SM) biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis.</p> <p>Methods</p> <p>The Adenovirus containing SMS2 gene was given into 10-week ApoE KO C57BL/6J mice by femoral intravenous injection. In the control group, the Adenovirus containing GFP was given. To confirm this model, we took both mRNA level examination (RT-PCR) and protein level examination (SMS activity assay).</p> <p>Result</p> <p>We generated recombinant adenovirus vectors containing either human SMS2 cDNA (AdV-SMS2) or GFP cDNA (AdV-GFP). On day six after intravenous infusion of 2 × 10¹¹particle numbers into ten-week-old apoE KO mice, AdV-SMS2 treatment significantly increased liver SMS2 mRNA levels and SMS activity (by 2.7-fold, 2.3-fold, p < 0.001, respectively), compared to AdV-GFP treated mice. Moreover, plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and sphingomyelin (SM) levels were significantly increased by 39% (p < 0.05), 42% (p < 0.05), 68% (p < 0.001), and 45% (p < 0.05), respectively. Plasma high-density lipoprotein cholesterol (HDL-C), phosphatidylcholine (PC), and PC/SM ratio were decreased by 42% (p < 0.05), 18% (p < 0.05), and 45% (p < 0.05), respectively. On day 30, the atherosclerotic lesions on the aortic arch of AdV-SMS2 treated mice were increased, and the lesion areas on the whole aorta and in the aortic root were significantly increased (p < 0.001). Furthermore, the collagen content in the aorta root was significantly decreased (p < 0.01).</p> <p>Conclusions</p> <p>Our results present direct morphological evidence for the pro-atherogenic capabilities of SMS2. SMS2 could be a potential target for treating atherosclerosis.</p

The role of mesenchymal stem cells derived exosomes as a novel nanobiotechnology target in the diagnosis and treatment of cancer

Mesenchymal stem cells (MSCs), one of the most common types of stem cells, are involved in the modulation of the tumor microenvironment (TME). With the advancement of nanotechnology, exosomes, especially exosomes secreted by MSCs, have been found to play an important role in the initiation and development of tumors. In recent years, nanobiotechnology and bioengineering technology have been gradually developed to detect and identify exosomes for diagnosis and modify exosomes for tumor treatment. Several novel therapeutic strategies bioengineer exosomes to carry drugs, proteins, and RNAs, and further deliver their encapsulated cargoes to cancer cells through the properties of exosomes. The unique properties of exosomes in cancer treatment include targeting, low immunogenicity, flexibility in modification, and high biological barrier permeability. Nevertheless, the current comprehensive understanding of the roles of MSCs and their secreted exosomes in cancer development remain inadequate. It is necessary to better understand/update the mechanism of action of MSCs-secreted exosomes in cancer development, providing insights for better modification of exosomes through bioengineering technology and nanobiotechnology. Therefore, this review focuses on the role of MSCs-secreted exosomes and bioengineered exosomes in the development, progression, diagnosis, and treatment of cancer

A Two-Year Surveillance of 2009 Pandemic Influenza A (H1N1) in Guangzhou, China: From Pandemic to Seasonal Influenza?

In this two-years surveillance of 2009 pandemic influenza A (H1N1) (pH1N1) in Guangzhou, China, we reported here that the scale and duration of pH1N1 outbreaks, severe disease and fatality rates of pH1N1 patients were significantly lower or shorter in the second epidemic year (May 2010-April 2011) than those in the first epidemic year (May 2009-April 2010) (P<0.05), but similar to those of seasonal influenza (P>0.05). Similar to seasonal influenza, pre-existing chronic pulmonary diseases was a risk factor associated with fatal cases of pH1N1 influenza. Different from seasonal influenza, which occurred in spring/summer seasons annually, pH1N1 influenza mainly occurred in autumn/winter seasons in the first epidemic year, but prolonged to winter/spring season in the second epidemic year. The information suggests a tendency that the epidemics of pH1N1 influenza may probably further shift to spring/summer seasons and become a predominant subtype of seasonal influenza in coming years in Guangzhou, China

Study of brain network alternations in non-lesional epilepsy patients by BOLD-fMRI

ObjectiveTo investigate the changes of brain network in epilepsy patients without intracranial lesions under resting conditions.MethodsTwenty-six non-lesional epileptic patients and 42 normal controls were enrolled for BOLD-fMRI examination. The differences in brain network topological characteristics and functional network connectivity between the epilepsy group and the healthy controls were compared using graph theory analysis and independent component analysis.ResultsThe area under the curve for local efficiency was significantly lower in the epilepsy patients compared with healthy controls, while there were no differences in global indicators. Patients with epilepsy had higher functional connectivity in 4 connected components than healthy controls (orbital superior frontal gyrus and medial superior frontal gyrus, medial superior frontal gyrus and angular gyrus, superior parietal gyrus and paracentral lobule, lingual gyrus, and thalamus). In addition, functional connectivity was enhanced in the default mode network, frontoparietal network, dorsal attention network, sensorimotor network, and auditory network in the epilepsy group.ConclusionThe topological characteristics and functional connectivity of brain networks are changed in in non-lesional epilepsy patients. Abnormal functional connectivity may suggest reduced brain efficiency in epilepsy patients and also may be a compensatory response to brain function early at earlier stages of the disease

Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding

Coronavirus M protein is an essential component of virion and plays pivotal roles in virion assembly, budding and maturation. The M protein is integrated into the viral envelope with three transmembrane domains flanked by a short amino-terminal ectodomain and a large carboxy-terminal endodomain. In this study, we showed co-purification of the M protein from coronavirus infectious bronchitis virus (IBV) with actin. To understand the cellular factors that may be involved in virion assembly, budding and maturation processes, IBV M was used as the bait in a yeast two-hybrid screen, resulting in the identification of β-actin as a potentially interacting partner. This interaction was subsequently confirmed by coimmunoprecipitation and immunofluorescence microscopy in mammalian cells, and mutation of amino acids A159 and K160 on the M protein abolished the interaction. Introduction of the A159-K160 mutation into an infectious IBV clone system blocks the infectivity of the clone, although viral RNA replication and subgenomic mRNA transcription were actively detected. Disruption of actin filaments with cell-permeable agent cytochalasin D at early stages of the infection cycle led to the detection of viral protein synthesis in infected cells but not release of virus particles to the cultured media. However, the same treatment at late stages of the infection cycle did not affect the release of virus particles to the media, suggesting that disruption of the actin filaments might block virion assembly and budding, but not release of the virus particles. This study reveals an essential function of actin in the replication cycle of coronavirus

Lpcat3 deficiency promotes palmitic acid-induced 3T3-L1 mature adipocyte inflammation through enhanced ROS generation

Phosphatidylcholines (PCs) are major phospholipids in the mammalian cell membrane. Structural remodeling of PCs is associated with many biological processes. Lysophosphatidylcholine acyltransferase 3 (Lpcat3), which catalyzes the incorporation of polyunsaturated fatty acyl chains into the sn-2 site of PCs, plays an important role in maintaining plasma membrane fluidity. Adipose tissue is one of the main distribution organs of Lpcat3, while the relationship between Lpcat3 and adipose tissue dysfunction during overexpansion remains unknown. In this study, we reveal that both polyunsaturated PC content and Lpcat3 expression are increased in abdominal adipose tissues of high-fat diet-fed mice when compared with chow-diet-fed mice, indicating that Lpcat3 is involved in adipose tissue overexpansion and dysfunction. Our experiments in 3T3-L1 adipocytes show that inhibition of Lpcat3 does not change triglyceride accumulation but increases palmitic acid-induced inflammation and lipolysis. Conversely, Lpcat3 overexpression exhibits anti-inflammatory and anti-lipolytic effects. Furthermore, mechanistic studies demonstrate that Lpcat3 deficiency promotes reactive oxygen species (ROS) generation by increasing NOX enzyme activity by facilitating the translocation of NOX4 to lipid rafts, thereby aggregating 3T3-L1 adipocyte inflammation induced by palmitic acid. Moreover, overexpression of Lpcat3 exhibits the opposite effects. These findings suggest that Lpcat3 protects adipocytes from inflammation during adipose tissue overexpansion by reducing ROS generation. In conclusion, our study demonstrates that Lpcat3 deficiency promotes palmitic acid-induced inflammation in 3T3-L1 adipocytes by enhancing ROS generation

Anti-corrosion behaviors of epoxy composite coatings enhanced via graphene oxide with different aspect ratios

Anti-corrosion behaviors of epoxy composite coatings enhanced via graphene oxide with different aspect ratio