Assessing the causal association between human blood metabolites and the risk of gout.

BACKGROUND: The occurrence of gout is closely related to metabolism, but there is still a lack of evidence on the causal role of metabolites in promoting or preventing gout. METHODS: We applied a two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and gout using genome-wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR-Egger, weighted median, Cochran's Q test, Egger intercept test, and leave-one-out analysis, were performed to assess the stability and reliability of the results. We also performed a metabolic pathway analysis to identify potential metabolic pathways. RESULTS: After screening, 486 metabolites were retained for MR analysis. After screening by IVW and sensitivity analysis, 14 metabolites were identified with causal effect on gout (P < 0.05), among which hexadecanedioate was the most significant candidate metabolite associated with a lower risk of gout (IVW OR = 0.50; 95% CI = 0.38-0.67; P = 1.65 × 10-6 ). Metabolic pathway analysis identified one pathway that may be associated with the disease. CONCLUSION: This MR study combining genomics with metabolomics provides a novel insight into the causal role of blood metabolites in the risk of gout, which implies that examination of certain blood metabolites would be a feasible strategy for screening populations with a higher risk of gout.

Personalized prediction for multiple chronic diseases by developing the multi-task Cox learning model.

Personalized prediction of chronic diseases is crucial for reducing the disease burden. However, previous studies on chronic diseases have not adequately considered the relationship between chronic diseases. To explore the patient-wise risk of multiple chronic diseases, we developed a multitask learning Cox (MTL-Cox) model for personalized prediction of nine typical chronic diseases on the UK Biobank dataset. MTL-Cox employs a multitask learning framework to train semiparametric multivariable Cox models. To comprehensively estimate the performance of the MTL-Cox model, we measured it via five commonly used survival analysis metrics: concordance index, area under the curve (AUC), specificity, sensitivity, and Youden index. In addition, we verified the validity of the MTL-Cox model framework in the Weihai physical examination dataset, from Shandong province, China. The MTL-Cox model achieved a statistically significant (p<0.05) improvement in results compared with competing methods in the evaluation metrics of the concordance index, AUC, sensitivity, and Youden index using the paired-sample Wilcoxon signed-rank test. In particular, the MTL-Cox model improved prediction accuracy by up to 12% compared to other models. We also applied the MTL-Cox model to rank the absolute risk of nine chronic diseases in patients on the UK Biobank dataset. This was the first known study to use the multitask learning-based Cox model to predict the personalized risk of the nine chronic diseases. The study can contribute to early screening, personalized risk ranking, and diagnosing of chronic diseases.

Sustainability assessment of small hydropower from an ESG perspective: A case study of the Qin-Ba Mountains, China.

Small hydropower (SHP) has made significant contributions to economic and social development in rural and remote mountainous regions. However, the adverse ecological-environmental impacts resulting from the SHP sector and challenges in hydropower management have become major areas of concern. From an Environmental, Social, and Governance (ESG) perspective and using three SHP stations (GXD, WZL, and SJB) in the Qin-Ba Mountains as case studies, we constructed a sustainability assessment system comprising 18 indicators across three dimensions. The hesitant fuzzy linguistic term sets (HFLTSs) and cloud models were employed to determine the sustainability level of SHP by characterizing the hesitancy of the evaluator and the uncertainty of the evaluated data. (1) The ecological-environmental protection (E) dimension was assigned the greatest weight, followed by the dimensions of social responsibility contribution (S) and corporate governance management (G). The weights of certain indicators, including the water qualification rate, river morphology maintenance, guaranteed rate of instream flow, comprehensive utilization, and production safety standardization grade were relatively high, conforming to the current context of green development prioritization in which ecological-environmental protection is of the utmost importance. (2) The overall sustainability levels of all three SHP stations were "good", with the E-dimension contributing the most and the G-dimension contributing the least to the sustainability goal. (3) The GXD, WZL, and SJB stations were ranked first, second, and third, respectively, in terms of their sustainability scores. This study provides an innovative perspective for the sustainability assessment of SHP. The evaluation method can be generalized to encompass multi-attribute decision-making problems. The findings of this study can aid in addressing the shortcomings associated with SHP development and promote sustainability within the SHP industry.

[Clinical and genetic analysis of a child with early-onset severe obesity].

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with early-onset severe obesity. METHODS: A child who presented at the Department of Endocrinology, Hangzhou Children's Hospital on August 5, 2020 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out on the child. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: This child was a 2-year-and-9-month girl featuring severe obesity with hyperpigmentation on the neck and armpit skin. WES revealed that she has harbored compound heterozygous variants of the MC4R gene, namely c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp). Sanger sequencing confirmed that they were respectively inherited from her father and mother. The c.831T>A (p.Cys277*) has been recorded by the ClinVar database. Its carrier frequency among normal East Asians was 0.000 4 according to the 1000 Genomes, ExAC, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as pathogenic. The c.184A>G (p.Asn62Asp) has not been recorded in the ClinVar, 1000 Genomes, ExAC and gnomAD databases. Prediction using IFT and PolyPhen-2 online software suggested it to be deleterious. Based on the guidelines from the ACMG, it was determined as likely pathogenic. CONCLUSION: The c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp) compound heterozygous variants of the MC4R gene probably underlay the early-onset severe obesity in this child. Above finding has further expanded the spectrum of MC4R gene variants and provided a reference for the diagnosis and genetic counseling for this family.

Genome-wide analysis of the rose (Rosa chinensis) NAC family and characterization of RcNAC091.

KEY MESSAGE: A genome-wide analysis identified 116 NAC genes in rose, including stress-related ones with different expression patterns under drought and salt stress. Silencing of RcNAC091, a member of the ATAF subfamily, decreased dehydration tolerance in rose. The NAC (NAM, ATAF, and CUC) transcription factors (TFs) are plant-specific proteins that regulate various developmental processes and stress responses. However, knowledge of the NAC TFs in rose (Rosa chinensis), one of the most important horticultural crops, is limited. In this study, 116 NAC genes were identified from the rose genome and classified into 16 subfamilies based on protein phylogenetic analysis. Chromosomal mapping revealed that the RcNAC genes were unevenly distributed on the seven chromosomes of rose. Gene structure and motif analysis identified a total of ten conserved motifs, of which motifs 1-7 were highly conserved and present in most rose NACs, while motifs 8-10 were present only in a few subfamilies. Further study of the stress-related RcNACs based on the transcriptome data showed differences in the expression patterns among the organs, at various floral developmental stages, and under drought and salt stress in rose leaves and roots. The stress-related RcNACs possessed cis-regulatory elements (CREs) categorized into three groups corresponding to plant growth and development, phytohormone response, and abiotic and biotic stress response. Reverse transcription-quantitative real-time PCR (RT-qPCR) analysis of 11 representative RcNACs revealed their differential expression in rose leaves and roots under abscisic acid (ABA), polyethylene glycol (PEG), and sodium chloride (NaCl) treatments. Furthermore, the silencing of RcNAC091 verified its role in positively regulating the dehydration stress response. Overall, the present study provides valuable insights into stress-related RcNACs and paves the way for stress tolerance in rose.

Physiological Functions of FBW7 in Metabolism.

FBW7 is the recognition subunit of the SCF (Skp1-Cullin1-F-box proteins) E3 ubiquitin ligase complex, and it determines the specificity of the SCF substrate. SCFFBW7 is a recognized tumor suppressor because of its ability to degrade many proto-oncogenic substrates. Recent studies have shown that FBW7 plays a key role in metabolism by targeting the degradation of critical regulators involved in cellular metabolism in a ubiquitin-dependent manner. Here, we review recent studies, which highlight the important role of FBW7 in metabolism.

Dexmedetomidine reduces dextran sulfate sodium (DSS)-induced NCM460 cell inflammation and barrier damage by inhibiting RhoA/ROCK signaling pathway.

OBJECTIVE: This study investigated the role of dexmedetomidine (DEX) in dextran sulfate sodium (DSS)-induced NCM460 cells. MATERIAL AND METHODS: The viability and apoptosis of NCM460 cells treated with DEX with or without DSS were detected by CCK-8 and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay. The level of inflammatory factors and expression of inflammation-related proteins, tight junction proteins and Ras homolog gene family, member A/Rho-associated coiled-coil containing protein kinase (RhoA/ROCK) signaling-related proteins in NCM460 cells treated with DEX and/or U46619 (RhoA/ROCK agonist) and/or DSS were detected by the respective enzyme-linked immunosorbent assay (ELISA) kits and Western blot analysis. The permeability of NCM460 monolayers was examined with transepithelial electrical resistance (TEER) assay. RESULTS: DEX had no effect on NCM460 cell viability. However, DEX improved the viability and barrier damage and suppressed the apoptosis and inflammation of DSS-induced NCM460 cells. Correspondingly, the expression of inflammation-related proteins was reduced and the expression of tight junction proteins was increased in DSS-induced NCM460 cells after treatment with DEX. In addition, RhoA/ROCK signaling was activated in NCM460 cells induced by DSS, which was suppressed by DEX. The protective effects of DEX on DSS-indued NCM460 cells were reversed by U46619. CONCLUSION: DEX improved viability and barrier damage while suppressed apoptosis and inflammation in DSS-indued NCM460 cells by inhibiting RhoA/ROCK signaling pathway.

Anthraquinones from the Aerial Parts of Rubia cordifolia with Their NO Inhibitory and Antibacterial Activities.

The present study aimed to identify the composition of the aerial parts of Rubia cordifolia L. A chemical investigation on the EtOAc extracts from the aerial parts of Rubia cordifolia resulted in the isolation of four new anthraquinones, namely Cordifoquinone A-D (1-4), along with 16 known anthraquinones. Their structures were elucidated on the basis of NMR and HR-ESIMS data. All isolates were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 1, 3 and 10 exhibited significant inhibitory activities with IC50 values of 14.05, 23.48 and 29.23 µmol·L-1, respectively. Their antibacterial activities of four bacteria, Escherichia coli (ATCC 25922), Staphylococcus aureus subsp. aureus (ATCC 29213), Salmonella enterica subsp. enterica (ATCC 14028) and Pseudomonas aeruginosa (ATCC 27853), were also evaluated. Our results indicated that the antibacterial activity of these compounds is inactive.

Integrated diversity and shared species analyses of human viromes.

Diversity analysis has been performed routinely on microbiomes, including human viromes. Shared species analysis has been conducted only rarely, but it can be a powerful supplement to diversity analysis. In the present study, we conducted integrated diversity and shared species analyses of human viromes by reanalyzing three published datasets of human viromes with more than 250 samples from healthy vs. diseased individuals and/or rural vs. urban individuals. We found significant differences in the virome diversity measured in the Hill numbers between the healthy and diseased individuals, with diseased individuals exhibiting higher virome diversity than healthy individuals, and rural individual exhibiting higher virome diversity than urban individuals. We applied both "read randomization" and "sample randomization" algorithms to perform shared species analysis. With the more conservative sample randomization algorithm, the observed number of shared species was significantly smaller than the expected shared species in 50% (8 of 16) of the comparisons. These results suggest that integrated diversity and shared species analysis can offer more comprehensive insights in comparing human virome samples than standard diversity analysis alone with potentially powerful applications in differentiating the effects of diseases or other meta-factors.

Sporadic hand, foot, and mouth disease cases associated with non-C4 enterovirus 71 strains in Xiamen, China, from 2009 to 2018.

Enterovirus 71 (EV71) has caused large hand, foot, and mouth disease (HFMD) epidemics among young children, and EV71 infection is the leading cause of severe HFMD cases and deaths. In mainland China, the prevalence and risk factors of non-C4 EV71 strains are still unclear. In this study, we monitored non-C4 strains over a 10-year HFMD epidemiological surveillance period in Xiamen. The 5'UTR and VP1 coding region of EV71 strains were amplified by RT-nested PCR and sequenced. Thirty-two non-C4 EV71 strains were identified during 2009-2018. This study provides important information about the prevalence of EV71 in China that will be applicable for development of vaccines and diagnostic reagents as well as establishment of policies for HFMD prevention and control.

Effects of 2,3',4,4',5-pentachlorobiphenyl exposure during pregnancy on DNA methylation in the testis of offspring in the mouse.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants, and the widespread use of PCBs has had adverse effects on human and animal health. This study experiment explored the effects of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on the mammalian reproductive system. PCB118 was administered to pregnant mice from 7.5 to 12.5 days of gestation; F1 mice were obtained and the reproductive system of F1 male mice was examined. PCB118 damaged the reproductive system in male F1 mice, as evidenced by negative effects on the testicular organ coefficient (testes weight/bodyweight), a decrease in the diameter of seminiferous tubules and a significant reduction in the anogenital distance in 35-day-old F1 mice. In addition, methylation levels of genomic DNA were reduced, with reductions in the expression of the DNA methyltransferases DNMT1, DNMT3A and DNMT3B, as well as that of the epigenetic regulatory factor ubiquitin like with PHD and ring finger domains 1 (Uhrf1). Together, the results of this study provide compelling evidence that exposure of pregnant mice to PCB118 during primordial germ cell migration in the fetus affects the reproductive system of the offspring and decreases global methylation levels in the testis.

Effects of intrauterine exposure to 2,3',4,4',5-pentachlorobiphenyl on the reproductive system and sperm epigenetic imprinting of male offspring.

Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3',4,4',5-pentachlorobiphenyl (PCB118) is one of the most important dioxin-like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant mice were exposed to 0, 20 and 100 µg/kg/day of PCB118 during the stage of fetal primordial germ cell migration. Compared with the control group, we found morphological alterations of the seminiferous tubules and a higher sperm deformity rate in the male offspring in the treatment groups. Furthermore, the methylation patterns in the treatment groups of the imprinted genes H19 and Gtl2 in the sperm were altered in the male offspring. We also characterized the disturbance of the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3a, Dnmt3b, Dnmt3l, and Uhrf1. The results indicated that intrauterine exposure to low doses of PCB118 could significantly damage the reproductive health of the male offspring. Therefore, attention should be paid to the adverse effects of PCB118 exposure during pregnancy on the reproductive system of male offspring.

Euodia pasteuriana Methanol Extract Exerts Anti-Inflammatory Effects by Targeting TAK1 in the AP-1 Signaling Pathway.

Euodia pasteuriana A. Chev. ex Guillaumin, also known as Melicope accedens (Blume) T.G. Hartley, is a herbal medicinal plant native to Vietnam. Although Euodia pasteuriana is used as a traditional medicine to treat a variety of inflammatory diseases, the pharmacological mechanisms related to this plant are unclear. This study aimed to investigate the anti-inflammatory effects of a methanol extract of Euodia pasteuriana leaves (Ep-ME) on the production of inflammatory mediators, the mRNA expression of proinflammatory genes, and inflammatory signaling activities in macrophage cell lines. The results showed that Ep-ME strongly suppressed the release of nitric oxide (NO) in RAW264.7 cells induced with lipopolysaccharide (LPS), pam3CysSerLys4 (Pam3CSK), and polyinosinic-polycytidylic acid (poly I:C) without cytotoxicity. A reverse transcription-polymerase chain reaction further confirmed that Ep-ME suppressed the expression of interleukin 6 (IL-6), matrix metalloproteinase-1 (MMP1), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-3 (MMP3), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP9) at the transcriptional level and reduced the luciferase activities of activator protein 1 (AP-1) reporter promoters. In addition, immunoblotting analyses of the whole lysate and nuclear fraction, as well as overexpression assays demonstrated that Ep-ME decreased the translocation of c-Jun and suppressed the activation of transforming growth factor beta-activated kinase 1 (TAK1) in the AP-1 signaling pathways. These results imply that Ep-ME could be developed as an anti-inflammatory agent that targets TAK1 in the AP-1 signaling pathway.

Tabebuia impetiginosa: A Comprehensive Review on Traditional Uses, Phytochemistry, and Immunopharmacological Properties.

Tabebuia impetiginosa, a plant native to the Amazon rainforest and other parts of Latin America, is traditionally used for treating fever, malaria, bacterial and fungal infections, and skin diseases. Additionally, several categories of phytochemicals and extracts isolated from T. impetiginosa have been studied via various models and displayed pharmacological activities. This review aims to uncover and summarize the research concerning T. impetiginosa, particularly its traditional uses, phytochemistry, and immunopharmacological activity, as well as to provide guidance for future research. A comprehensive search of the published literature was conducted to locate original publications pertaining to T. impetiginosa up to June 2020. The main inquiry used the following keywords in various combinations in titles and abstracts: T. impetiginosa, Taheebo, traditional uses, phytochemistry, immunopharmacological, anti-inflammatory activity. Immunopharmacological activity described in this paper includes its anti-inflammatory, anti-allergic, anti-autoimmune, and anti-cancer properties. Particularly, T. impetiginosa has a strong effect on anti-inflammatory activity. This paper also describes the target pathway underlying how T. impetiginosa inhibits the inflammatory response. The need for further investigation to identify other pharmacological activities as well as the exact target proteins of T. impetiginosa was also highlighted. T. impetiginosa may provide a new strategy for prevention and treatment of many immunological disorders that foster extensive research to identify potential anti-inflammatory and immunomodulatory compounds and fractions as well as to explore the underlying mechanisms of this herb. Further scientific evidence is required for clinical trials on its immunopharmacological effects and safety.

3,3',4,4',5-Pentachlorobiphenyl influences mitochondrial apoptosis pathway in granulosa cells.

3,3',4,4',5-Polychlorinated biphenyl (PCB126) is a persistent organic environmental pollutant which can affect various biological activities of organisms, such as immunity, neurological function, and reproduction. In our study, we aimed to investigate the effects of PCB126 on granulosa cells (GCs). GCs were collected from ovaries in PMSG-treated mice, after 24 hours culture. GCs were then incubated with 10 pg/mL, 100 pg/mL, and 10 ng/mL of PCB126 for another 24 hours. Following these steps, exposed GCs were collected for further experimentation. Our data showed that the number of GCs in the 10 ng/mL PCB126 decreased. Meanwhile, pyknotic nuclei and condensed chromatin increased, while the apoptotic cells in the 10 ng/mL PCB126 group were significantly increased. Furthermore, the expression of the apoptotic executive protein caspase-3 increased after PCB126 treatment. The expression of Bax, Bcl-2, and Bim related to the mitochondrial apoptosis pathway were also influenced to different degrees. Thus, our data suggested that PCB126 affect the GCs apoptosis, and mitochondrial apoptosis pathway was involved in this process.

The Effects of miR-195-5p/MMP14 on Proliferation and Invasion of Cervical Carcinoma Cells Through TNF Signaling Pathway Based on Bioinformatics Analysis of Microarray Profiling.

BACKGROUND/AIMS: This study is aimed at identification of miR-195-5p/MMP14 expression in cervical cancer (CC) and their roles on cell proliferation and invasion profile of CC cells through TNF signaling pathway in CC. METHODS: Microarray analysis, gene set enrichment analysis (GSEA) and DAVID were used to analyze differentially expressed miRNAs, mRNAs and signaling pathways. MiR-195-5p and MMP14 expression levels in CC cell were determined by qRT-PCR. Western blot was employed to measure MMP14 and TNF signaling pathway-relating protein level. Luciferase reporter system was used to confirm the targeting relationship between MMP14 and miR-195-5p. Cell proliferation and invasion was respectively deeded by CCK8, transwell. In vivo experiment was carried out to study the impact of MMP14 and miR-195-5p on CC development in mice. RESULTS: The microarray analysis and the results of qRT-PCR determined that miR-195-5p was under-expressed and MMP14 was over-expressed in CC cells. GSEA and DAVID analysis showed that TNF signaling pathway was regulated by miR-195-5p/MMP14 and activated in cervical carcinoma cells. The miR-195-5p and MMP14 have a negative regulation relation. In vivo experiment found that down-regulated MMP14 and up-regulated miR-195-5p suppressed the tumor development. CONCLUSION: Our results suggest that MMP14 is a direct target of miR-195-5p, and down-regulated MMP14 and up-regulated miR-195-5p suppressed proliferation and invasion of CC cells by inhibiting TNF signaling pathway.

Transcription factor AP-2ß suppresses cervical cancer cell proliferation by promoting the degradation of its interaction partner ß-catenin.

Transcription factor AP-2ß mediates the transcription of a number of genes implicated in mammalian development, cell proliferation, and carcinogenesis. Although the expression pattern of AP-2ß has been analyzed in cervical cancer cell lines, the functions and molecular mechanism of AP-2ß are unknown. Here, we found that AP-2ß significantly inhibits TCF/LEF reporter activity. Moreover, AP-2ß and ß-catenin interact both in vitro through GST pull-down assays and in vivo by co-immunoprecipitation. We further identified the interaction regions to the DNA-binding domain of AP-2ß and the 1-9 Armadillo repeats of ß-catenin. Moreover, AP-2ß binds with ß-TrCP and promotes the degradation of endogenous ß-catenin via the proteasomal degradation pathway. Immunohistochemistry analysis revealed a negative correlation between the two proteins in cervical cancer tissues and cell lines. Finally, functional analysis showed that AP-2ß suppresses cervical cancer cell growth in vitro and in vivo by inhibiting the expression of Wnt downstream genes. Taken together, these findings demonstrated that AP-2ß functions as a novel inhibitor of the Wnt/ß-catenin signaling pathway in cervical cancer.

In vitro and in vivo evaluation of folate-mediated PEGylated nanostructured lipid carriers for the efficient delivery of furanodiene.

Furanodiene (FN) loaded FA-PEG2000-DSPE modified nanostructured lipid carriers (FA-FN-NLCs) were developed to increase the solubility and bioavailability of FN, prolong the circulation time in blood and improve the targeting ability. FA-FN-NLCs were prepared using emulsification-ultrasonic and low temperature-solidification method and optimized by central composition design (CCD). In vitro and in vivo characteristics of FA-FN-NLCs were investigated in detail. The optimized formulations exhibited a spherical shape with particle size of 127.4 ± 2.62 nm, PDI of 0.268 ± 0.04, zeta potential of -14.7 ± 1.08 mV, high encapsulation efficiency of 89.04 ± 2.26% and loading capacity of 8.46 ± 0.20%. Differential scanning calorimetry (DSC) indicated that FN was not in crystalline state in FA-FN-NLCs. In vitro drug release exhibited a biphasic release pattern which showed a relative burst drug release at the initial time and followed by a prolonged drug release. In vivo, compared with FN solution (FN-SOL) and FN loaded traditional NLCs (FN-NLCs), FA-FN-NLCs had a longer blood circulating time (t1/2) and higher area under the curve (AUC). NiR fluorescence imaging study demonstrated that FA-FN-NLCs specially accumulated in tumor site by the receptor-mediated endocytosis. This study showed that FA-FN-NLCs was a promising drug delivery system for FN in the treatment of cancer.

Danshen enhanced the estrogenic effects of Qing E formula in ovariectomized rats.

BACKGROUND: Menopause is characterized by a decrease in life quality due to the appearance of uncomfortable symptoms. Nowadays, Understanding menopause-associated pathophysiology and developing new strategies to improve the treatment of menopausal-associated symptoms is an important issue. Our study was to evaluate the synergistic effects of Danshen (salvia miltiorrhiza bunge) and the phytoestrogenic effects of 3 modified Qing E formulas, to explore a better formula for menopausal disorders. METHODS: 100 rats were randomized into 5 groups: Sham (Sham operation group), OVX (model group of ovariectomized rat), BDL (group with low concentration of Qing E Formula), BDH (group with high concentration of Qing E Formula) and BDD (group with high concentration of Qing E Formula Plus Danshen), receiving vehicle and extract of different modified Qing E formula respectively. The food intake, body weight, uterus weight, blood levels of triglycerides (TG), total cholesterol (TC) and cholesterol fractions were assessed. The mammary glands and uterus were morphologically analyzed. The bone density of tibias were measured by peripheral quantitative computed tomography (pQCT). Additionally, luciferase induction assays were performed in Hela cells with the mixtures derived from Qing E formula plus Danshen (BDD). RESULTS: Qing E formula plus Danshen significantly increased the uterus wet weight, enhanced the thickness of uterine wall, endometrial epithelium and glandular epithelium, improved trabecular bone and total density evidently, reduced the levels of low density lipoprotein cholesterol (LDL-C) and TG, possessed notable estrogen receptor beta (ERß) and estrogen receptor alpha (ERα) agonist activity. CONCLUSION: Qing E formula plus Danshen exerted more evident estrogen-like effects, thus it has a potential therapeutic use to treat menopausal disorders.

Pioglitazone lowers serum retinol binding protein 4 by suppressing its expression in adipose tissue of obese rats.

BACKGROUND/AIMS: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4), an adipocytokine associated with obesity and insulin resistance. METHODS: Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting. RESULTS: Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells. CONCLUSION: These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects.