Hepatitis B Virus Infection and Increased Risk of Gestational Diabetes Regardless of Liver Function Status: A Xiamen Area Population-Based Study.

Background & Aims: Hepatitis B virus (HBV) infection is a significant cause of liver function damage. However, previous studies on HBV mainly aimed at ordinary people, and there is a lack of consensus on the relationship between HBV infection and gestational diabetes mellitus (GDM) and whether HBV-infected pregnant women should undergo antiviral treatment. In addition, systematic studies on the impact of HBV infection on GDM have rarely been studied directly. Therefore, the overall goal of this study was to pursue the association between HBV infection, liver function, and GDM using Xiamen area gestational big data. Methods: Using the Xiamen Primary Health Information System-maternal and child health information system, the data on participants (138,867 in total) expected confinement between 2008 and 2018 were included. Using univariate and multivariate logistic regressions, we constructed models to determine the role of HBV infection and liver function status in GDM. In addition, an analysis of variance tests was performed to study whether the relationship between HBsAg and GDM differed in the normal liver function and the abnormal liver function subgroups. Results: HBsAg's positive status showed a substantial correlation with GDM onset in univariate and multivariate logistic regressions (p < 0.001). Subgroup analysis among HBsAg, liver function, and GDM suggests that both HBsAg and liver function affect the onset of GDM and have the highest prevalence of both abnormalities. Furthermore, ANOVA was used to investigate the association of HBsAg positive (p < 0.001), abnormal liver function (p < 0.001), and their interaction (p = 0.302) on the onset of GDM. This result showed that HBsAg is an independent factor of GDM pathogenesis, regardless of liver function status. Conclusion: HBsAg and liver function are independent factors in GDM. Therefore, regarding these results, while clinicians consider the traditional risk factors of GDM, it is necessary to consider the HBV infection status. Conducting a dietary intervention for HBsAg-positive pregnant women at the early stage of pregnancy is conducive to reducing the adverse effects.

Association of pre- and early-pregnancy factors with the risk for gestational diabetes mellitus in a large Chinese population.

Gestational diabetes mellitus (GDM) has aroused wide public concern, as it affects approximately 1.8-25.1% of pregnancies worldwide. This study aimed to examine the association of pre-pregnancy demographic parameters and early-pregnancy laboratory biomarkers with later GDM risk, and further to establish a nomogram prediction model. This study is based on the big obstetric data from 10 "AAA" hospitals in Xiamen. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. Data are analyzed using Stata (v14.1) and R (v3.5.2). Total 187,432 gestational women free of pre-pregnancy diabetes mellitus were eligible for analysis, including 49,611 women with GDM and 137,821 women without GDM. Irrespective of confounding adjustment, eight independent factors were consistently and significantly associated with GDM, including pre-pregnancy body mass index (BMI), pre-pregnancy intake of folic acid, white cell count, platelet count, alanine transaminase, albumin, direct bilirubin, and creatinine (p < 0.001). Notably, per 3 kg/m2 increment in pre-pregnancy BMI was associated with 22% increased risk [adjusted odds ratio (OR) 1.22, 95% confidence interval (CI) 1.21-1.24, p < 0.001], and pre-pregnancy intake of folic acid can reduce GDM risk by 27% (adjusted OR 0.73, 95% CI 0.69-0.79, p < 0.001). The eight significant factors exhibited decent prediction performance as reflected by calibration and discrimination statistics and decision curve analysis. To enhance clinical application, a nomogram model was established by incorporating age and above eight factors, and importantly this model had a prediction accuracy of 87%. Taken together, eight independent pre-/early-pregnancy predictors were identified in significant association with later GDM risk, and importantly a nomogram modeling these predictors has over 85% accuracy in early detecting pregnant women who will progress to GDM later.

Exploring the mechanism of PingTang No.5 capsule on nonalcoholic fatty liver disease through network pharmacology and experimental validation.

PingTang No.5 capsule (PT5), a modified Traditional Chinese Medicine (TCM) formula of Zexie Decoction, is used to treat patients with lipid metabolism disorders in our hospital. The present study was designed to investigate the mechanisms of PT5 in treating non-alcoholic fatty liver disease (NAFLD). PT5 information including ingredients, pharmacological properties, and potential targets was obtained from TCM databases. The candidate targets of PT5 were predicted by network pharmacological analysis, and the possible pathway and mechanism were obtained from DAVID database, followed by experimental validation in NAFLD mice model treated with PT5. Total 328 compounds were selected using the threshold oral bioactivity (OB) > 30% or drug-likeness (DL) > 0.1 of pharmacology characteristic, and 1033 candidate targets obtained to construct the network analysis. The 113 targets were selected from the intersection between candidate targets of PT5 and NAFLD relative gene. These targets were evaluated in diabetic complications, cancer, Hepatitis B, Fluid shear stress and atherosclerosis, and TNF signaling pathway. TNF-α was the important factor in protein interaction analysis of STRING and involved in the lipid regulation and oxidative stress in NAFLD. When administrated to the NAFLD mice, PT5 reduced weight, blood fatty acids, decreased the adipocyte size, and improved the metabolism. Besides, the molecular verification of lipid metabolism increased and oxidative stress reduced that interpreted the mechanism of PT5 preventing liver cell from lipid accumulation and injury of NAFLD. These results presented PT5 have the potential therapy as an alternative treatment for NAFLD.

Anthocyanins from black rice (Oryza sativa L.) demonstrate antimetastatic properties by reducing MMPs and NF-κB expressions in human oral cancer CAL 27 cells.

Aside from the commonly known white rice lines, colored varieties also exist. These varieties have historically been used in Chinese medicine. Anthocyanins, a large group of natural polyphenols existing in a variety of daily fruits and vegetables, have been widely recognized as cancer chemopreventive agents. The primary objective of cancer treatment strategies has traditionally focused on preventing the occurrence of metastasis. In this research the antimetastatic mechanism of anthocyanins on the invasion/migration of human oral CAL 27 cells was performed using a transwell to quantify the migratory potential of CAL 27 cells and the results show that anthocyanins can inhibit the in vitro migration and invasion of CAL 27 cancer cells. In addition, the gelatin zymography assay indicated that anthocyanins inhibited the activity of matrix metalloproteinases-2 (MMP-2). Western blotting assay also demonstrated that anthocyanins inhibited the associated protein expression of migration/invasion of CAL 27 cell. Immunofluorescence staining proved that anthocyanins inhibited nuclear factor kappa B p65 (NF-κB p65) expressions. These results demonstrated that anthocyanins from a species of black rice (selected purple glutinous indica rice cultivated at Asia University) could suppress CAL 27 cell metastasis by reduction of MMP-2, MMP-9, and NF-κB p65 expression through the suppression of PI3K/Akt pathway and inhibition of NF-κB levels.

Investigation of estrogen receptor (ESR1) for breast cancer from traditional Chinese medicine.

Recently, an important topic of breast cancer had been published in 2013. In this report, estrogen receptor (ESR1) had defined the relation of hormone-cause breast cancer. The screening of traditional Chinese medicine (TCM) database has found the molecular compounds by simulating molecular docking and molecular dynamics to regulate ESR1. S-Allylmercaptocysteine and 5-hydroxy-L-tryptophan are selected according to the highest docking score than that of other TCM compounds and Raloxifene (control). The simulation from molecular dynamics is helpful in analyzing and detecting the protein-ligand interactions. After a comparing the control and the Apo form, then based on the docking poses, hydrophobic interactions, hydrogen bond and structure variations, this research postulates that S-allylmercaptocysteine may be more appropriate than other compounds for protein-ligand interaction.

Investigation of potent lead for acquired immunodeficiency syndrome from traditional Chinese medicine.

Acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), has become, because of the rapid spread of the disease, a serious global problem and cannot be treated. Recent studies indicate that VIF is a protein of HIV to prevent all of human immunity to attack HIV. Molecular compounds of traditional Chinese medicine (TCM) database filtered through molecular docking and molecular dynamics simulations to inhibit VIF can protect against HIV. Glutamic acid, plantagoguanidinic acid, and Aurantiamide acetate based docking score higher with other TCM compounds selected. Molecular dynamics are useful for analysis and detection ligand interactions. According to the docking position, hydrophobic interactions, hydrogen bonding changes, and structure variation, the study try to select the efficacy of traditional Chinese medicine compound Aurantiamide acetate is better than the other for protein-ligand interactions to maintain the protein composition, based on changes in the structure.

Lead screening for HIV-1 integrase (IN) inhibited by traditional Chinese medicine.

Human immunodeficiency virus causes the acquired immunodeficiency syndrome (AIDS) and becomes a serious world-wide problem because of this disease's rapid propagation and incurability. Integrase strand transfer inhibitors (INSTIs) supports HIV have rapid drug resistance for antitreatment. Screening the traditional Chinese medicine (TCM) database by simulating molecular docking and molecular dynamics may select molecular compounds to inhibit INSTIs against HIV drug resistance. (S)-cathinone and (1S,2S)-norpseudoephedrine are selected based on structure and ligand-based drugs are designed and then get higher bioactivity predicted score from SVM than Raltegravir and other TCM compounds. The molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions and hydrogen bond variations define the main regions of important amino acids in integrase. In addition to the detection of TCM compound efficacy, we suggest (1S,2S)-norpseudoephedrine is better than the others based on the analysis of interaction and the effect on the structural variation.

An investigation of small GTPases in relation to liver tumorigenesis using traditional Chinese medicine.

Recently, an important topic of liver tumorigenesis had been published in 2013. In this report, Ras and Rho had defined the relation of liver tumorigenesis. The traditional Chinese medicine (TCM) database has been screened for molecular compounds by simulating molecular docking and molecular dynamics to regulate Ras and liver tumorigenesis. Saussureamine C, S-allylmercaptocysteine, and Tryptophan are selected based on the highest docking score than other TCM compounds. The molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. Based on the docking poses, hydrophobic interactions, and hydrogen bond variations, this research surmises are the main regions of important amino acids in Ras. In addition to the detection of TCM compound efficacy, we suggest Saussureamine C is better than the others for protein-ligand interaction.

Possible inhibitor from traditional Chinese medicine for the ß form of calcium-dependent protein kinase type II in the treatment of major depressive disorder.

Recently, an important topic of major depressive disorder (MDD) had been published in 2013. MDD is one of the most prevalent and disabling mental disorders. Consequently, much research is being undertaken into the causes and treatment. It has been found that inhibition of the ß form of calcium/calmodulin-dependent protein kinase type II (ß-CaMKII) can ameliorate the disorder. Upon screening the traditional Chinese medicine (TCM) database by molecular docking, sengesterone, labiatic acid, and methyl 3-O-feruloylquinate were selected for molecular dynamics. After 20 ns simulation, the RMSD, total energy, and structure variation could define the protein-ligand interaction. Furthermore, sengesterone, the principle candidate compound, has been found to have an effect on the regulation of emotions and memory development. In structure variation, we find the sample functional group of important amino acids make the protein stable and have limited variation. Due to similarity of structure variations, we suggest that these compounds may have an effect on ß-CaMKII and that sengesterone may have a similar efficacy as the control. However labiatic acid may be a stronger inhibitor of ß-CaMKII based on the larger RMSD and variation.

In silico investigation of traditional Chinese medicine compounds to inhibit human histone deacetylase 2 for patients with Alzheimer's disease.

Human histone deacetylase 2 (HDAC2) has been identified as being associated with Alzheimer's disease (AD), a neuropathic degenerative disease. In this study, we screen the world's largest Traditional Chinese Medicine (TCM) database for natural compounds that may be useful as lead compounds in the search for inhibitors of HDAC2 function. The technique of molecular docking was employed to select the ten top TCM candidates. We used three prediction models, multiple linear regression (MLR), support vector machine (SVM), and the Bayes network toolbox (BNT), to predict the bioactivity of the TCM candidates. Molecular dynamics simulation provides the protein-ligand interactions of compounds. The bioactivity predictions of pIC50 values suggest that the TCM candidatesm, (-)-Bontl ferulate, monomethylcurcumin, and ningposides C, have a greater effect on HDAC2 inhibition. The structure variation caused by the hydrogen bonds and hydrophobic interactions between protein-ligand interactions indicates that these compounds have an inhibitory effect on the protein.

Insight into HIV of IFN-induced myxovirus resistance 2 (MX2) expressed by traditional Chinese medicine.

Recently, an important topic of the acquired immunodeficiency syndrome (AIDS) had been published in 2013. In this report, the expression of the IFN-induced myxovirus resistance 2 (MX2) had been defined the function to kill the human immunodeficiency virus (HIV). The screening from the Traditional Chinese Medicine (TCM) database by simulating molecular docking and molecular dynamics could select candidate compounds, which may express MX2 against HIV. Saussureamine C, Crotalaburnine, and Precatorine are selected based on the highest docking score and other TCM compounds. The data from molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions, and hydrogen bond with structure variations, this research could assess the interaction between protein and ligand interaction. In addition to the detection of TCM compound efficacy, we suggest that Saussureamine C is better than the others in protein-ligand interaction and the structural variation to express MX2.

The inhibition of folylpolyglutamate synthetase (folC) in the prevention of drug resistance in Mycobacterium tuberculosis by traditional Chinese medicine.

Tuberculosis (TB) is an infectious disease caused by many strains of mycobacteria, but commonly Mycobacterium tuberculosis. As a possible method of reducing the drug resistance of M. tuberculosis, this research investigates the inhibition of Folylpolyglutamate synthetase, a protein transcript from the resistance association gene folC. After molecular docking to screen the traditional Chinese medicine (TCM) database, the candidate TCM compounds, with Folylpolyglutamate synthetase, were selected by molecular dynamics. The 10,000 ps simulation in association with RMSD analysis and total energy and structural variation defined the protein-ligand interaction. The selected TCM compounds Saussureamine C, methyl 3-O-feruloylquinate, and Labiatic acid have been found to inhibit the activity of bacteria and viruses and to regulate immunity. We also suggest the possible pathway in protein for each ligand. Compared with the control, similar interactions and structural variations indicate that these compounds might have an effect on Folylpolyglutamate synthetase. Finally, we suggest Saussureamine C is the best candidate compound as the complex has a high score, maintains its structural composition, and has a larger variation value than the control, thus inhibiting the drug resistance ability of Mycobacterium tuberculosis.

Lead screening for CXCR4 of the human HIV infection receptor inhibited by traditional Chinese medicine.

The acquired immunodeficiency syndrome (AIDS) is a serious worldwide disease caused by the human immunodeficiency virus (HIV) infection. Recent research has pointed out that the G protein-coupled chemokine receptor CXCR4 and the coreceptor C-C chemokine receptor type 5 (CCR5) are important targets for HIV infection. The traditional Chinese medicine (TCM) database has been screened for candidate compounds by simulating molecular docking and molecular dynamics against HIV. Saussureamine C, 5-hydroxy-L-tryptophan, and diiodotyrosine are selected based on the highest docking score. The molecular dynamics is helpful in the analysis and detection of protein-ligand interactions. According to the analysis of docking poses, hydrophobic interactions, hydrogen bond variations, and the comparison of the effect on CXCR4 and CCR5, these results indicate Saussureamine C may have better effect on these two receptors. But for some considerations, diiodotyrosine could make the largest variation and may have some efficacy contrary to expectations.

In Silico Investigation of Cytochrome P450 2C9 in relation to Aging Using Traditional Chinese Medicine.

Cytochrome P450 2C9 (CYP2C9) metabolizes dehydroepiandrosterone-sulfate (DHEA-S), but in elderly people the amount of DHEA-S remaining after CYP2C9 metabolization may be insufficient for optimal health. A prediction model, molecular docking, and molecular dynamics were used to screen the Traditional Chinese Medicine (TCM) database to determine molecular compounds that may inhibit CYP2C9. The candidate compounds apocynoside(I), 4-methoxymagndialdehyde, and prunasin have higher Dock Scores, and prediction bioactivity than warfarin (the control drug). The interaction between 4-methoxymagndialdehyde and CYP2C9 is more intense than with other TCM compounds, but the simulation is longer. In these compounds, apocynoside(I) and prunasin have a greater number of pathways for their flexible structure, but these structures create weak interactions. These candidate compounds, which are known to have antioxidation and hypolipidemic functions that have an indirect effect on the aging process, can be extracted from traditional Chinese medicines. Thus, these candidate compounds may become CYP2C9 inhibitors and play an important role in providing optimal health in the elderly.

In Silico Insight into Potent of Anthocyanin Regulation of FKBP52 to Prevent Alzheimer's Disease.

Alzheimer's disease (AD) is caused by the hyperphosphorylation of Tau protein aggregation. FKBP52 (FK506 binding protein 52) has been found to inhibit Tau protein aggregation. This study found six different kinds of anthocyanins that have high binding potential. After analyzing the docking positions, hydrophobic interactions, and hydrogen bond interactions, several amino acids were identified that play important roles in protein and ligand interaction. The proteins' variation is described using eigenvectors and the distance between the amino acids during a molecular dynamics simulation (MD). This study investigates the three loops based around Glu85, Tyr113, and Lys121-all of which are important in inducing FKBP52 activation. By performing a molecular dynamic simulation process between unbound proteins and the protein complex with FK506, it was found that ligand targets that docked onto the FK1 domain will decrease the distance between Glu85/Tyr113 and Glu85/Lys121. The FKBP52 structure variation may induce FKBP52 activation and inhibit Tau protein aggregation. The results indicate that anthocyanins might change the conformation of FKBP52 during binding. In addition, the purple anthocyanins, such as cyanidin-3-glucoside and malvidin-3-glucoside, might be better than FK506 in regulating FKBP52 and treating Alzheimer's disease.

Lead Screening for HIV of C-C Chemokine Receptor Type 5 Receptor Inhibited by Traditional Chinese Medicine.

The acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), has become a serious world-wide problem because of this disease's rapid propagation and incurability. Recent research has pointed out that the C-C chemokine receptor type 5 (CCR5) is an important target for HIV infection. The traditional Chinese medicine (TCM) database (http://tcm.cmu.edu.tw/) has been screened for molecular compounds that, by simulating molecular docking and molecular dynamics, may protect CCR5 against HIV. Saussureamine C, 5-hydroxy-L-tryptophan, and abrine are selected based on the docking score being higher than Maraviroc and other TCM compounds. The molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions, and hydrogen bond variations, this research surmises TRP86, TYR108, GLN194, TYR251, and GLU283 are the main regions of important amino acids in CCR5. In addition to the detection of TCM compound efficacy, we suggest saussureamine C is better than the others for maintaining protein composition during protein-ligand interaction, based on the structural variation.

A high-pressure infrared spectroscopic study on the interaction of ionic liquids with PEO-PPO-PEO block copolymers and 1,4-dioxane.

We have investigated the effect of pressure on imidazolium C-H---O interactions in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide (EMI(+)TFSA(-))/L64 and EMI(+)TFSA(-)/1,4-dioxane mixtures. The addition of Pluronic L64 to EMI(+)TFSA(-) leads to appreciable changes in band frequencies and shapes of the imidazolium C-H stretching bands. A possible explanation is the formation of C-H---O interactions between imidazolium C-H groups and oxygen atoms of polyethylene oxides (PEOs). In other words, L64 can be added to change the relative contribution of the isolated and associated components of EMI(+)TFSA(-). In contrast to L64, the oxygen atoms of 1,4-dioxane cannot perturb the local structures of imidazolium C-H groups of EMI(+)TFSA(-) and the association configuration is still favored in the presence of 1,4-dioxane. As the pressure is elevated, 1,4-dioxane molecules tend to associate with themselves and TFSA(-) interacts with EMI(+) to form associated configurations. Our results suggest the formation of association between EMI(+) cation and L64 and the complexes are stable up to the pressure of 2.5 GPa.