PubMed Health⌕ Search

Biomedical subjects

Guang Wang

Publications and source records attributed to Guang Wang.

11 recordsLinked to original sources

Single-Cell Transcriptome-Wide Mendelian Randomization and Colocalization Uncover Potential Immunocytes-Related Therapeutic Targets for Obesity.

Weight-loss treatment is crucial for individuals with obesity to prevent various complications. The role of Immune cells in obesity has been recently recognized, whereas its translation into therapy requires identifying key target genes. We performed Mendelian randomization (MR) analysis to assess causal relationships between expression quantitative trait loci (eQTL) of 14 immune cells and obesity-related traits (obesity, body mass index and body fat percentage), and validated the results in colocalization analysis. For the putative causal genes identified by the MR and colocalization analyses, we conducted pathway enrichment, differential expressed gene (DEG) analysis and search of druggable evidence, and utilized a Tier system to prioritize drug targets for obesity. MR and colocalization evidence was observed for 1630 genes associated with one or more obesity-related traits, mainly expressed in CD4+ naive/central memory T cells and enriched in antigen processing and presentation pathways. Forty-one genes showed causal relationship with all three outcomes, among which 19 genes have not been reported for obesity previously. DEG analysis using single-cell RNA sequencing data of blood or adipose tissue indicated that the differential expression of UBE2Z in monocytes, ZCCHC7 in T cells, and FNBP4 in B cells between lean and obese individuals were consistent with the MR results. By searching drug-gene interaction databases, we found targeted drugs for PYGB and PRUNE1, and PYGB was the top gene ranked in the Tier system. This study provides evidence for the involvement of immune cells in obesity, and the potential cell-specific, immune-related targets for obesity treatment.

Obesity↗

Photochemical phase transition versus photochemical phase separation.

When a nematic liquid crystal is doped with a large amount of a liquid crystalline azobenzene compound (15 wt %), the photoisomerization of azobenzene under UV and visible light irradiation can give rise to reversible and interconvertible photochemical phase transition and photochemical phase separation. Both normal and reverse modes of photocontrolled switching of transmittance through crossed polarizers can be realized with the same mixture of liquid crystal/azobenzene dopant.

Journal Article↗

Temporal changes in the inequality of early growth of Cunninghamia lanceolata (Lamb.) Hook.: a novel application of the Gini coefficient and Lorenz asymmetry.

Growth within tree populations varies among individuals due to changes in biotic and abiotic factors. The degree of such variation, defined as growth inequality, serves as a useful indicator of the uniformity of growth within a population in response to the prevalent environmental conditions. By application of the Gini coefficient (G), an index for inequality, we characterized the early growth inequality of ninety crosses of Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) and their open-pollinated parental lines. Tree cumulative height was measured annually for 8 consecutive years. Both the crosses and parental lines exhibited temporal changes in growth inequality. The inequality of total height among the crosses decreased logarithmically with age by nearly 3-fold after 13 growing seasons, suggesting that tree height became less variable among the crosses as trees grew larger. Interestingly, the Lorenz asymmetry, an index reflecting the shape of the Lorenze curve from which G is derived, revealed that the inequality of annual height increment among the crosses resulted from an alternate contribution of the fast-growing and slow-growing trees. Among parental lines, two provenances with the smallest and the largest overall inequality in total height showed a similar pattern of changes in annual growth inequality, and the provenance differences were consistent over time. Compared to the other provinces, a local provenance exhibited less variation in total height among individual trees as reflected by a smaller value of inequality, and was better adapted to the field conditions. Our results demonstrated the sensitivity and usefulness of the Gini coefficient and Lorenz asymmetry for the analysis of growth inequality in non-natural populations. Growth inequality is a potentially useful evaluation criterion for early selection. Given comparable initial growth, provenances/families with lower growth inequality values would likely outperform those with higher growth inequality, and eventually tree size of the latter would be more variable due to greater variations among individual trees. Assessment of growth inequality at early ages will advance our understanding of variability of tree growth within a population, facilitate forest genetics improvement programs, and enhance the efficiency of tree breeding.

China↗

How can azobenzene block copolymer vesicles be dissociated and reformed by light?

The underlying mechanism of UV light-induced dissociation and visible light-induced reformation of vesicles formed by an azobenzene diblock copolymer was investigated. These processes were studied in situ by monitoring changes in optical transmittance of the vesicular solution while being exposed to UV or visible light irradiation. The results indicate that the UV-induced dissociation of the vesicles results from their thermodynamic instability due to a shift of the hydrophilic/hydrophobic balance arising from the trans-cis isomerization, while their reaggregation takes place upon visible light irradiation that shifts the hydrophilic/hydrophobic balance in the opposite direction after the reverse cis-trans isomerization. The study suggests a specific design principle for obtaining UV light-dissociable and visible light-recoverable vesicles based on azobenzene block copolymers. On one hand, the structure of azobenzene moiety used in the hydrophobic block should have a small (near zero) dipole moment in the trans form and a significantly higher dipole moment in the cis form, which ensures a significant increase in polarity of the hydrophobic block under UV light irradiation. On the other hand, the hydrophilic block should be weakly hydrophilic. The conjunction of the two conditions can make the light-induced shift of the hydrophilic/hydrophobic balance important enough to lead to the reversible change in vesicular aggregation.

Journal Article↗

Folic acid reverses hyper-responsiveness of LPS-induced chemokine secretion from monocytes in patients with hyperhomocysteinemia.

Our previous study demonstrated that homocysteine (Hcy) mediated the expression and secretion of MCP-1 and IL-8 in human monocytes. In the present study, we investigated whether the responsiveness of isolated monocytes to lipopolysaccharide (LPS)-induced chemokine secretion was enhanced in patients with hyperhomocysteinemia (HHcy), and if so, whether this enhanced response could be inhibited by folic acid treatment. We studied 38 control subjects and 40 patients with HHcy. The results showed that MCP-1 secretion from isolated monocytes in response to low-dose LPS in patients with HHcy was significantly higher than that in controls. After patients with HHcy underwent low-dose folic acid treatment (0.8 mg/d) for 6 months, plasma Hcy levels were decreased and the hyper-responsiveness of MCP-1 and IL-8 secreted by isolated monocytes was significantly reversed. Furthermore, folic acid treatment at high concentrations (5 microM) significantly reduced the elevated levels of reactive oxygen species, NADPH oxidase activity and chemokines in response to Hcy in cultured human monocytes. HHcy may contribute to atherogenesis through enhancing the responsiveness of monocytes to inflammatory stimuli and promoting leukocyte recruitment into atherosclerotic plaque. In addition to lowering the plasma levels of Hcy, low-dose folic acid treatment exerts beneficial effects on patients with HHcy by inhibiting pro-inflammatory responses such as chemokine secretion from human monocytes.

Arteriosclerosis↗

Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces clinical inflammatory responses in type 2 diabetes with coronary artery disease after coronary angioplasty.

Rosiglitazone, an agonist of peroxisome proliferator-activated receptor-gamma (PPAR gamma ), is an insulin-sensitizing antidiabetic agent and inhibits restenosis in animal blood vessels. However, its benefit for patients with type 2 diabetes and coronary artery disease (CAD) after percutaneous coronary intervention is unknown. Patients with diabetes and CAD who had undergone percutaneous coronary intervention were randomized to either receive or not receive rosiglitazone (4 mg/d) for 6 months. After 6 months of rosiglitazone treatment, the plasma levels of fasting glucose and insulin and those of hemoglobin A1C and homeostasis model assessment of insulin resistance were significantly decreased in the rosiglitazone group as compared with baseline levels and those in the control group. After 2 and 6 months of rosiglitazone treatment, the plasma level of high-density lipoprotein was significantly increased in the rosiglitazone group. In addition, plasma levels of monocyte chemoattractant protein-1 and C-reactive protein and hyperresponsiveness of low-dose lipopolysaccharide-induced monocyte chemoattractant protein-1 secretion from monocytes were reduced. Furthermore, the occurrence of coronary events was significantly decreased in the rosiglitazone group at 6-month follow-up. Our data indicate that rosiglitazone may protect the vascular wall through not only improving the features of metabolic disorders but also reducing proinflammatory responses and the occurrence of coronary events in patients with diabetes and CAD after percutaneous coronary intervention.

Aged↗

Chemokine RANTES is upregulated in monocytes from patients with hyperhomocysteinemia.

AIM: To investigate the changes in plasma level of the chemokine RANTES (regulated upon activation, normal T cells expressed and secreted) and the responsiveness of lipopolysaccharide (LPS)-induced RANTES secretion from monocytes in patients with hyperhomocysteinemia (HHcy). METHODS: The plasma levels of homocysteine (Hcy), folate, and RANTES were measured in 38 control patients with normal Hcy levels and 40 patients with HHcy and the mRNA synthesis of RANTES in isolated human monocytes was determined by RNase protection assays. RESULTS: The plasma level of RANTES was elevated in HHcy patients compared with controls (median 5.3 vs 3.5 ng/mL, P<0.01). LPS-induced RANTES production from monocytes of HHcy patients was also increased significantly. In addition, Hcy directly increased the mRNA level of RANTES in isolated normal human monocytes in a time- and dose-dependent manner. CONCLUSION: Upregulated RANTES from monocytes in HHcy patients may be involved in the atherogenesis of HHcy-induced atherosclerosis.

Adult↗

Effect of homocysteine on plaque formation and oxidative stress in patients with acute coronary syndromes.

BACKGROUND: Cardiovascular diseases, especially coronary artery disease (CAD), are major causes of death in industrialized countries. Elevated concentrations of plasma homocysteine (Hcy) have been associated with an increased risk of CAD. Increased plasma levels of chemokine, characterized by their ability to induce migration and activation of leukocytes, may contribute to the pathogenesis of CAD. This study was designed to investigate the changes of plasma Hcy, monocyte chemoattractant protein-1 (MCP-1) and oxidative stress markers in acute coronary syndrome patients. METHODS: A total of 149 subjects were divided into four groups: 50 patients with unstable angina, 30 patients with acute myocardial infarction, 20 coronary restenosis patients after percutaneous coronary intervention and 49 healthy control subjects. Plasma levels of Hcy, MCP-1, malondialdehyde and superoxide dismutase were measured. RESULTS: Plasma levels of Hcy and MCP-1 showed significant increases in unstable angina, acute myocardial infarction and restenosis patients compared with control subjects (P < 0.05, respectively). Plasma levels of malondialdehyde were significantly increased in unstable angina and acute myocardial infarction patients when compared with control subjects (P < 0.05, respectively). Plasma superoxide dismutase levels were significantly reduced in acute myocardial infarction patients when compared with control group (P < 0.01). CONCLUSION: Hcy might act as an atherogenic factor through promoting chemokine, reactive oxygen species and oxidized low density lipoprotein production and thereby convert a stable plaque into an unstable potentially occlusive lesion.

Acute Disease↗

Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure.

Nitric oxide (NO) inhibits vascular contraction by activating cGMP-dependent protein kinase I-alpha (PKGI-alpha), which causes dephosphorylation of myosin light chain (MLC) and vascular smooth muscle relaxation. Here we show that PKGI-alpha attenuates signaling by the thrombin receptor protease-activated receptor-1 (PAR-1) through direct activation of regulator of G-protein signaling-2 (RGS-2). NO donors and cGMP cause cGMP-mediated inhibition of PAR-1 and membrane localization of RGS-2. PKGI-alpha binds directly to and phosphorylates RGS-2, which significantly increases GTPase activity of G(q), terminating PAR-1 signaling. Disruption of the RGS-2-PKGI-alpha interaction reverses inhibition of PAR-1 signaling by nitrovasodilators and cGMP. Rgs2-/- mice develop marked hypertension, and their blood vessels show enhanced contraction and decreased cGMP-mediated relaxation. Thus, PKGI-alpha binds to, phosphorylates and activates RGS-2, attenuating receptor-mediated vascular contraction. Our study shows that RGS-2 is required for normal vascular function and blood pressure and is a new drug development target for hypertension.

Animals↗