Oxymatrine Alleviates High-Fat-High-Fructose-Induced Fatty Liver in Rats: Understanding the Molecular Mechanism Through an Untargeted Metabonomics Study.

Objective: Previous studies have shown that oxymatrine (OMT) can improve high-fat-high-fructose-diet-induced non-alcoholic fatty liver disease (NAFLD), and our study aimed to explore its possible metabolic potential mechanisms. Methods: Wistar rats were fed a high-fat-high-fructose diet for 8 weeks and treated with oxymatrine by gavage for the last 4 weeks. We measured biochemical indicators and pathological changes in each group and used liquid chromatography-mass spectrometry (LC-MS) to analyze changes in metabolites in the serum and liver of the rats. Results: The results showed that OMT can alleviate the high-fat-high-fructose-induced weight gain and hepatic lipid deposition in rats. Metabolomic analysis showed that the level of eicosapentaenoic acid (EPA) was downregulated and levels of desmosterol and d-galactose were upregulated in livers fed with HFDHFr. The levels of L-isoleucine, L-valine, arachidonic acid (AA), taurocholic acid (TCA), chenodeoxycholyltaurine (TDCA), isocitrate, and glutathione (GSH) were downregulated in the liver, whereas those of linoleic acid (LA), phosphocholine (PC), glycerophosphocholine (GPC), and oxidized glutathione (GSSG) were upregulated in the serum treated with OMT. Conclusion: In summary, OMT can improve HFDHFr-induced NAFLD, and metabolomic analysis can provide an early warning for the development of NAFLD as well as provide a rationale for therapeutic targets.

Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer.

Introduction: Emerging evidence demonstrates that the high-fructose and high-fat diet (HFHF) induced obesity and fatty liver disease has become one of the most common metabolic disorders worldwide. Therefore, innovative investigations on compounds targeting obesity and fatty liver diseases are urgently needed. Methods: The high-throughput natural compounds screen was performed to screen the important compounds. A rat HFHF model was constructed, the regulatory function of Oxymatrine in HFHF-induced obesity was further explored. Results: We identified Oxymatrine, a natural compound extracted from Sophora flavescens, showed a potential compacity in high-fat diet-induced fatty liver disease. We found that oxymatrine significantly inhibited HFHF-induced obesity using a rat HFHF model. Additionally, we found that oxymatrine altered the enhancer landscape of subcutaneous adipose tissues by ChIP-seq analysis using antibodies against the H3K27ac histone modification. Motif enrichment analysis showed the Smad motif was significantly enriched in enhancers altered post-oxymatrine treatment. Further chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis and luciferase reporter assays showed oxymatrine alters the binding of Smad3 on the enhancer regions of B-cell lymphoma 2 (Bcl2) and the enhancer activity of Bcl2. Discussion: Together, our study highlighted oxymatrine could suppress high-fructose and high-fat diet-induced obesity by inhibiting the suppressor of mothers against decapentaplegic 3 (Smad3) binding on obesity-related enhancers.

Retinal Microvascular Diameters are Associated with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the association between retinal microvascular diameters and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 690 patients with T2DM were included in this retrospective study. Patients were divided into DKD and non-DKD groups according to urine microalbumin/creatinine ratio and estimated glomerular filtration rate. Retinal microvascular diameters were measured by the automated retinal image analysis system. Multivariate logistic regression analysis and restricted cubic splines were used to assess the relationships between the retinal microvascular diameters and DKD in patients with T2DM. Results: Multivariate logistic regression showed that widened diameters of retinal venules and narrowed diameters of retinal arterioles were associated with DKD after adjusting for potential confounding variables. There was a significant linear trend between the diameters of superior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.080), inferior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.111) and central retinal venular equivalent (CRVE) (P for trend < 0.001, P for non-linearity = 0.392) and risk of DKD in patients with T2DM. The restricted cubic splines showed that narrowed retinal arteriolar diameters, superior and inferior nasal retinal venulas were associated with the risk of DKD in a non-linear fashion (all P for non-linearity < 0.001). Conclusion: Wider retinal venular diameters and narrower retinal arteriolar diameters were associated with an increased risk of DKD in patients with T2DM. Widened retinal venular diameters, especially CRVE, superior and inferior temporal retinal venula, were positively associated with an increased risk of DKD in a linear fashion. In contrast, narrowed retinal arteriolar diameters were associated with the risk of DKD in a non-linear fashion.

Relationship between geriatric nutritional risk index and osteoporosis in type 2 diabetes in Northern China.

BACKGROUND: Osteoporosis is a very common bone disease in the elderly population and can lead to fractures and disability. Malnutrition can lead to osteoporosis. The geriatric nutritional risk index (GNRI) is a tool used to assess the risk of malnutrition and complications associated with nutritional status in older patients and is a crucial predictor of many diseases. Hence, this study investigated the association between the GNRI and the presence of osteoporosis and assessed the value of this index for predicting osteoporosis in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study enrolled 610 elderly patients with T2DM. General and laboratory data of the patients were collected, along with their measurements of bone mineral density (BMD). The GNRI was calculated based on ideal body weight and serum albumin (ABL) levels. Correlation analysis was performed to determine the relationship between the GNRI and BMD and bone metabolism indices. The GNRI predictive value for osteoporosis development was analyzed through logistic regression analysis and by creating a receiver operating characteristic curve (ROC), calculating the area under the curve (AUC). RESULTS: All patients were divided into the no-nutritional risk and nutritional risk groups. Compared with the no-nutritional risk group, the nutritional risk group had a longer diabetes course, older age, higher HbA1c levels, higher prevalence of osteoporosis; lower BMI, ABL,triglyceride (TG),Calcium (Ca),25-hydroxy-vitamin-D(25(OH)D),and parathyroid hormone(PTH) and lower femoral neck BMD,total hip BMD (P < 0.05). All patients were also assigned to the non-osteoporosis and osteoporosis groups. The non-osteoporosis group had higher GNRI values than the osteoporosis group (P < 0.05). Correlation analysis revealed a positive correlation between the GNRI and lumbar BMD, femoral neck BMD, and total hip BMD (P < 0.05). After the adjustment for confounding factors, Spearman's correlation analysis revealed that the GNRI was positively correlated with Ca, 25(OH)D, and PTH and negatively correlated with alkaline phosphatase (ALP) and procollagen of type-1 N-propeptide (P1NP). Regression analysis exhibited that the GNRI was significantly associated with osteoporosis. The ROC curve analysis was performed using the GNRI as the test variable and the presence of osteoporosis as the status variable. This analysis yielded an AUC for the GNRI of 0.695 and was statistically significant (P < 0.05). CONCLUSIONS: A lower GNRI among T2DM patients in northern China is associated with a higher prevalence of osteoporosis.

Quantitative proteomics analysis based on tandem mass tag labeling coupled with labeling coupled with liquid chromatography-tandem mass spectrometry discovers the effect of silibinin on non-alcoholic fatty liver disease in mice.

In recent years, the beneficial effects of silibinin (SIL) on nonalcoholic fatty liver disease (NAFLD) have attracted widespread attention. We tried to study the intervention effect of SIL on NAFLD, and explore the potential mechanisms and targets of SIL on NAFLD improvement. Thirty-three male C57BL6/J mice were divided into three groups, and, respectively, fed a normal diet (ND), a high-fat diet (HFD) or a HFD given SIL treatment (HFD+SIL). Biochemical indexes and histopathological changes of mice in each group were detected. In addition, quantitative proteomics analysis based on tandem mass tag (TMT) labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis was performed on protein changes in the livers. SIL could reduce the weight of mice, reduce liver lipid deposition, and improve glucose metabolism. Through comparison among the three experimental groups, a total of 30 overlapping proteins were found. These identified proteins were closely linked to liver lipid metabolism and energy homeostasis. Moreover, some drug targets were found, namely perilipin-2, phosphatidate phosphatase LPIN1, farnesyl pyrophosphate synthase, and glutathione S-transferase A1. In conclusions, high-fat diet increases the expressions of proteins implicated in lipid synthesis and transport in the liver, which can result in disorders of liver lipid metabolism. SIL can decrease liver lipid deposition and increase insulin sensitivity by regulating the expressions of these proteins. It not only improves the disorder of lipid metabolism in vivo, but also improves the disorder of glucose metabolism.

Alteration of the fatty acid composition of Brassica napus L. via overexpression of phospholipid: Diacylglycerol acyltransferase 1 from Sapium sebiferum (L.) Roxb.

Sapium sebiferum (L.) Roxb. plays an important role in traditional Chinese medicine and is one of major woody oil tree in China. Phospholipid: diacylglycerol acyltransferase 1 (PDAT1), as an important catalytic enzyme for the formation of triacylglycerol (TAG), is mainly responsible for the transfer of an acyl group from the sn-2 position of phospholipids to the sn-3 position of sn-1, 2-diacylglycerol (DAG) to produce TAG and sn-1 lysophospholipids. The importance of PDAT1 in triacylglycerol biosynthesis has been illustrated in previous research, and at least 67 PDAT1 sequences have been identified from 31 organisms. However, little is known about the gene encoding PDAT1 in S. sebiferum (SsPDAT1), which is involved in seed oil biosynthesis. To explore the functional characteristics of SsPDAT1, we cloned and analyzed the full-length cDNA in the coding region of SsPDAT1, which consists of 2040 bp and encodes a putative protein of 680 amino acid (aa) residues. Thin-layer chromatography (TLC) analysis showed that recombinant SsPDAT1 could restore TAG accumulation in TAG-deficient mutant yeast (Saccharomyces cerevisiae) H1246, which revealed the enzyme activity of SsPDAT1. Moreover, transgenic Brassica napus L. W10 plants overexpressing SsPDAT1 showed significant increases of 19.6-28.9 % in linoleic acid levels but decreases of 27.3-37.1 % in linolenic acid. Furthermore, the total oil content increased by 8.1 %-10.8 % in SsPDAT1 transgenic seeds. These results confirmed the role of SsPDAT1 in stabilizing oil biosynthesis and suggested that SsPDAT1 could be exploitable to specifically regulate the oil composition of plants. These experimental results provide a new concept that may enable the industrial development of plants with high-linoleic-acid oil through overexpression of SsPDAT1 in S. sebiferum L.

Research advances of WRINKLED1 (WRI1) in plants.

WRINKLED 1 (WRI1), a member of the AP2/EREBP class of transcription factors, regulates carbon allocation between the glycolytic and fatty acid biosynthetic pathways and plays important roles in other biological events. Previous studies have suggested that post-translational modifications and interacting partners modulate the activity of WRI1. We systematically summarised the structure of WRI1 as well as its molecular interactions during transcription and translation in plants. This work elucidates the genetic evolution and regulatory functions of WRI1 at the molecular level and describes a new pathway involving WRI1 that can be used to produce triacylglycerols (TAGs) in plants.

Magneto-Capillary Particle Dynamics at Curved Interfaces: Time-Varying Fields and Drop Mixing.

Spatially uniform magnetic fields induce nonzero forces on magnetic particles adsorbed at curved liquid interfaces thereby driving their motion. Such motions, prohibited in bulk fluids, arise due to interfacial constraints that couple magnetic torques to capillary forces at curved interfaces. Here, we show that time-varying (spatially uniform) magnetic fields can be used to drive a variety of steady particle motions on water drops in decane. Upon application of a precessing field, magnetic Janus particles with amphiphilic surface chemistry move either along circular orbits at the drop poles or along zigzag paths at the drop equator. The different magneto-capillary motions depend on the frequency and precession angle of the field as well as the initial position of the particle on the drop surface. Our experimental observations are reproduced and explained by a mathematical model that accounts for the relevant magnetic, capillary, and hydrodynamic forces and torques that contribute to particle motion. In addition to ferromagnetic Janus particles, we show that similar dynamics can be achieved using superparamagnetic carbonyl iron particles, which are manufactured on industrial scales and respond to even weaker magnetic fields. We demonstrate how the field-driven motion of such particles at the drop interface can induce fluid flows that effectively mix the drop interior. These results suggest that magneto-capillary particle motions could be used to enhance mass transfer within emulsions stabilized by magnetic particles.

Magneto-capillary dynamics of amphiphilic Janus particles at curved liquid interfaces.

A homogeneous magnetic field can exert no net force on a colloidal particle. However, by coupling the particle's orientation to its position on a curved interface, even static homogeneous fields can be used to drive rapid particle motions. Here, we demonstrate this effect using magnetic Janus particles with amphiphilic surface chemistry adsorbed at the spherical interface of a water drop in decane. Application of a static homogeneous field drives particle motion to the drop equator where the particle's magnetic moment can align parallel to the field. As explained quantitatively by a simple model, the effective magnetic force on the particle scales linearly with the curvature of the interface. For particles adsorbed on small droplets such as those found in emulsions, these magneto-capillary forces can far exceed those due to magnetic field gradients in both magnitude and range. This mechanism may be useful in creating highly responsive emulsions and foams stabilized by magnetic particles.

Directed Motion of Metallodielectric Particles by Contact Charge Electrophoresis.

We investigate the dynamics of metallodielectric Janus particles moving via contact charge electrophoresis (CCEP) between two parallel electrodes. CCEP uses a constant voltage to repeatedly charge and actuate conductive particles within a dielectric fluid, resulting in rapid oscillatory motion between the electrodes. In addition to particle oscillations, we find that micrometer-scale Janus particles move perpendicular to the field at high speeds (up to 600 µm/s) and over large distances. We characterize particle motions and propose a mechanism based on the rotation-induced translation of the particle following charge transfer at the electrode surface. The propulsion mechanism is supported both by experiments with fluorescent particles that reveal their rotational motions and by simulations of CCEP dynamics that capture the relevant electrostatics and hydrodynamics. We also show that interactions among multiple particles can lead to repulsion, attraction, and/or cooperative motions depending on the position and phase of the respective particle oscillators. Our results demonstrate how particle asymmetries can be used to direct the motions of active colloids powered by CCEP.