Scramblases and virus infection.

The asymmetric distribution of lipids, maintained by flippases/floppases and scramblases, plays a pivotal role in various physiologic processes. Scramblases are proteins that move phospholipids between the leaflets of the lipid bilayer of the cellular membrane in an energy-independent manner. Recent studies have indicated that viral infection is closely related to cellular lipid distribution. The level and distribution of phosphatidylserine (PtdSer) in cells have been demonstrated to be critical regulators of viral infections. Previous studies have supported that the infection of human immunodeficiency virus (HIV), Zika virus, Ebola virus (EBOV), influenza virus, and dengue fever virus require the externalization of phospholipids mediated by scramblases, which are also involved in the pathogenicity of the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we review the relationship of scramblases with viruses and the potential viral effector proteins that might utilize host scramblases.

Holothuria Leucospilota polysaccharides alleviate hyperlipidemia via alteration of lipid metabolism and inflammation-related gene expression.

Hyperlipemia is becoming a chronic disease that threatens human health. At the same time, people pay more and more attention to hyperlipemia. Holothuria Leucospilota polysaccharide (HLP) has been reported to ameliorate hyperlipidemia in high-fat diet-induced rats. Therefore, this study aimed to explore further metabolomics' role in improving liver function and reveal its mechanism. After oral administration of HLP for 4 weeks, total cholesterol (TC) and triglycerides (TG) levels of the liver in 100 and 200 mg/kg HLP groups were both decreased significantly (p < .05). The results showed that serum AST and ALT activity decreased by professing to be convinced of HLP. HLP also exerted antioxidant activities and up-regulated the expression of ACC, CD36, TNF-α and NF-κB in the liver of diabetic rats. Six potential biomarkers were recognized by UPLC-Q-TOF/MS and OPLS-DA. HLP alleviated liver injury by regulating the contents of metabolic end products in the serum of hyperlipidemic rats, such as nadolol and glycodeoxycholic acid. The results indicated that HLP effectively relieved HFD-induced hyperlipidemia by regulating metabolic disorders. PRACTICAL APPLICATIONS: As a chronic disease, hyperlipidemia has attracted more and more attention. Studies have shown that HLP regulates dyslipidemia, oxidative damage and inflammation to relieve hyperlipidemia. It mainly improved the liver damage caused by hyperlipidemia by inhibiting the expression of hepatic lipogenesis, oxidative stress and inflammatory factors. At the same time, we also detected six metabolites, among which high GDCA content indicated serious liver damage. Therefore, in the future, it can be suggested that HLP may be used as a functional, active substance in health products to assist in relieving hyperlipidemia, and GDCA may be used as an essential metabolic marker for the degree of liver injury.

Beneficial Effects of Holothuria leucospilota Polysaccharides on Fermentability In Vivo and In Vitro.

This work aimed to investigate the in-vitro and in-vivo fermentation behaviors of Holothuria leucospilota Polysaccharides (HLP) and the impact on mouse liver antioxidant activity. HLP showed excellent fermentability during in vitro experiments, which was characterized by increased levels of total sugar consumption and short-chain fatty acids (SCFAs). During in vitro fecal fermentation, the fucose contents in the HLP fermentation products (0.174 mg/mL) were higher than those of xylose and galactosamine during the first three hours, and fucose disappeared after 24 h. The concentrations of the generated SCFAs increased to 111.13 mmol/mL after in-vitro fermentation at 48 h. After 28 days of oral administration, the SCFA contents that were detected in the feces of mice treated with high HLP doses were significantly higher than those in the feces of mice treated with lower doses and the normal group. In addition, histological observations demonstrated that HLP increased the number of goblet cells without causing hepatocellular injury. Moreover, the increased glutathione peroxidase (GSH-Px) and superoxidase dismutase (SOD) activities and decreased malondialdehyde (MDA) contents in the mouse livers treated with HLP suggested the good performance of HLP with respect to liver antioxidants.

TMEM41B and VMP1 are phospholipid scramblases.

TMEM41B and VMP1, two endoplasmic reticulum (ER)-resident transmembrane proteins, play important roles in regulating the formation of lipid droplets (LDs), autophagy initiation, and viral infection. However, the biochemical functions of TMEM41B and VMP1 are unclear. A lipids distribution screen suggested TMEM41B and VMP1 are critical to the normal distribution of cholesterol and phosphatidylserine. Biochemical analyses unveiled that TMEM41B and VMP1 have scramblase activity. These findings shed light on the mechanism by which TMEM41B and VMP1 regulate LD formation, lipids distribution, macroautophagy, and viral infection.

TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine.

TMEM41B and VMP1 are integral membrane proteins of the endoplasmic reticulum (ER) and regulate the formation of autophagosomes, lipid droplets (LDs), and lipoproteins. Recently, TMEM41B was identified as a crucial host factor for infection by all coronaviruses and flaviviruses. The molecular function of TMEM41B and VMP1, which belong to a large evolutionarily conserved family, remains elusive. Here, we show that TMEM41B and VMP1 are phospholipid scramblases whose deficiency impairs the normal cellular distribution of cholesterol and phosphatidylserine. Their mechanism of action on LD formation is likely to be different from that of seipin. Their role in maintaining cellular phosphatidylserine and cholesterol homeostasis may partially explain their requirement for viral infection. Our results suggest that the proper sorting and distribution of cellular lipids are essential for organelle biogenesis and viral infection.

Sweet potato starch addition together with partial substitution of tilapia flesh effectively improved the golden pompano (Trachinotus blochii) surimi quality.

In order to improve the gel performance and edible quality of surimi for sustainable manufacture, the present study explored the feasibility of four kinds of starchs (potato, corn, sweet potato, and wheat) and fresh water fish tilapia as additives for golden pompano based surimi production. Sweet potato starch stood out as the most appropriate additive for golden pompano surimi due to the highest gel strength, lowest expressible moisture content and more compact microstructure. When the tilapia flesh substitution ratio reached 30%, best gel property of tilapia-golden pompano compound surimi with best texture property and whiteness value was achieved. Moreover, addition of 5% sweet potato starch to the golden pompano-tilapia (7:3) compound surimi comparatively obtained the optimal effect. Namely, it was observed that the texture parameters with hardness (3.62 N), gumminess (2.74 N), chewiness (17.35 mJ), cohesiveness (4.918), and springiness (0.872) being biggest values. On the other hand, the gel strength and expressible moisture content were 2,137.31 g. mm and 3.52%, respectively, which were overwhelming than other levels. Simultaneously, the whiteness of 5% addition group was 74.75, which was also a little higher than other groups. In summary, partial substitution of tilapia and proper addition of sweet potato starch effectively improved the gel performance and quality of golden pompano-based surimi products, which has potential applications in the industry of surimi.

A sea cucumber (Holothuria leucospilota) polysaccharide improves the gut microbiome to alleviate the symptoms of type 2 diabetes mellitus in Goto-Kakizaki rats.

Diabetes mellitus has become a worldwide concern in recent years. In this study, the effect of Holothuria leucospilota polysaccharide (HLP) on type 2 diabetes mellitus (T2DM) was investigated in Goto-Kakizaki (GK) rats. The results showed that HLP significantly improved glucose intolerance and regulated blood lipid and hormone levels (p < 0.05). Pathological analysis showed that HLP repaired the impairments of the pancreas and colon in diabetic rats. In addition, a high dose of HLP (200 mg/kg) significantly upregulated the gene expression of peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB/AKT), glucose transporter-4 (GLUT4) and anti-apoptotic (Bcl-2), and downregulated the mRNA levels of pro-apoptotic (Bax) and cluster of differentiation 36 (CD36) in diabetic rats (p < 0.05). Furthermore, HLP treatment increased the short-chain fatty acid-producing bacteria and decreased the opportunistic bacterial pathogen in the feces of diabetic rats. These results demonstrated that HLP has the potential to ameliorate T2DM in GK rats.

Holothuria Leucospilota Polysaccharides Ameliorate Hyperlipidemia in High-Fat Diet-Induced Rats via Short-Chain Fatty Acids Production and Lipid Metabolism Regulation.

Holothuria leucospilota polysaccharides (HLP) are expected to become potential resources for the treatment of hyperlipidemia because of their various bioactivities. In the study, the treatment of HLP on improving hyperlipidemia in rats was explored. Oral administration of HLP at 100 or 200 mg/kg body weight effectively alleviated serum lipid levels and liver histological abnormalities in high-fat-diet rats. HLP regulated abnormal mRNA, lipogenesis-related hormones and inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interleukin-12) levels. HLP improved the ability of gut microbiota to produce short-chain fatty acids (SCFAs). SCFAs have been found to ameliorate liver lesions. Therefore, HLP alleviated hyperlipidemia by improving the levels of SCFAs to regulate lipid metabolism. These results indicated that HLP could be used as beneficial polysaccharides to alleviate hyperlipidemia.

The effects of EGCG on the mechanical, bioactivities, cross-linking and release properties of gelatin film.

The effects of (-)-epigallocatechin gallate (EGCG) on the mechanical, antioxidative, antimicrobial, cross-linking and release properties of gelatin film were evaluated. The biofilm exhibited excellent antioxidant and antibacterial activities against Staphylococcus aureus and Escherichia coli in the presence of EGCG at more than 3%. With the increasing content of EGCG (1%-5%), higher denaturation temperature (66.5-84.6 °C) and bloom strength (609.3-1114.7 g) and denser microstructure suggested the existence of cross-linking bonds in the biofilm. The infrared spectroscopy, protein pattern and release property of EGCG showed that hydrogen bonds were the main driving force for cross-linking of the biofilm. The release of EGCG from the biofilm system was described and two compounds were cross-linked via hydrogen bonds. Thus, this study confirmed the improvement on mechanical, bioactivities and release properties of the biofilm was most likely due to the interactions between gelatin and EGCG.

Stem of SL1 RNA in HIV-1: structure and nucleocapsid protein binding for a 1 x 3 internal loop.

The 5'-leader of HIV-1 RNA controls many viral functions. Nucleocapsid (NC) domains of gag-precursor proteins select genomic RNA for packaging by binding several sites in the leader. One is likely to be a stem defect in SL1 that can adopt either a 1 x 3 internal loop, SL1i (including G247, A271, G272, G273) or a 1 x 1 internal loop (G247 x G273) near a two-base bulge (A269-G270). It is likely that these two conformations are both present and exchange readily. A 23mer RNA construct described here models SL1i and cannot slip into the alternate form. It forms a 1:1 complex with NCp7, which interacts most strongly at G247 and G272 (K(d) = 140 nM). This demonstrates that a linear G-X-G sequence is unnecessary for high-affinity binding. The NMR-based structure shows an easily broken G247:A271 base pair. G247 stacks on both of its immediate neighbors and A271 on its 5'-neighbor; G272 and G273 are partially ordered. A bend in the helix axis between the SL1 stems on either side of the internal loop is probable. An important step in maturation of the virus is the transition from an apical loop-loop interaction to a dimer involving intermolecular interactions along the full length of SL1. A bend in the stem may be important in relieving strain and ensuring that the strands do not become entangled during the transition. A stem defect with special affinity for NCp7 may accelerate the rate of the dimer transformation. This complex could become an important target for anti-HIV drug development, where a drug could exert its action near a high-energy intermediate on the pathway for maturation of the dimer.