Deciphering the enigma between low bioavailability and high anti-hepatic fibrosis efficacy of Yinchen Wuling powder based on drug metabolism and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Yinchen Wuling powder (YCWLP) is a famous traditional Chinese medicine formula with the effect of "removing jaundice and eliminating dampness", which has the potential to prevent and treat hepatic fibrosis (HF). However, the mechanism of the active ingredients of YCWLP in treating HF remains to be clarified. AIM OF THE STUDY: This study aims to investigate the in vivo metabolic profile of YCWLP and the mechanism of its gut microbiota-mediated therapeutic effect on HF via network pharmacology. MATERIALS AND METHODS: In this comprehensive study, the UHPLC-FT-ICR-MS platform was used for the systematic characterization of the in vivo metabolic profile of YCWLP, and the mediating effect of gut microbiota was elucidated by comparing the differences of metabolites between the normal rats and pseudo germ-free rats administrated with YCWLP. Then, the identified active ingredients of YCWLP metabolized by gut microbiota and their targets associated with HF were used for further network pharmacological analysis, including the construction of PPI network, GO and KEGG enrichment and compound-target-pathway-disease network. RESULTS: Overall, 41 prototype compounds and 138 metabolites were identified in the biosamples after YCWLP administration. Among them, 15 drug prototypes are clearly metabolized by gut microbiota, and 91 metabolites showed significant differences between the N-YCWLP group and the PGF-YCWLP group, which might be attributed to the mediation of gut microbiota. Network pharmacology studies on the aforementioned 15 prototype components indicated crucial roles of arginine biosynthesis and complement and coagulation cascades-related genes such as PLG, NOS3, GC and F2 in the treatment of HF by YCWLP mediated by gut microbiota. CONCLUSIONS: The therapeutic effects of multiple active ingredients in YCWLP on HF depend on the metabolism of gut microbiota. This study offers novel insights into the relationship between bioactive chemical constituents and the action mechanism of YCWLP against HF.

Bile acids metabolism involved in the beneficial effects of Danggui Shaoyao San via gut microbiota in the treatment of CCl4 induced hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Shaoyao San (DSS) is a traditional Chinese medicine (TCM) first recorded in the Synopsis of the Golden Chamber. DSS has proven efficacy in treating hepatic fibrosis (HF). However, the effects and mechanisms of DSS on HF are not clear. AIM OF THE STUDY: To investigate the effect of DSS on HF via gut microbiota and its metabolites (SCFAs, BAs). MATERIALS AND METHODS: HF rats were induced with CCl4 and treated with DSS. Firstly, the therapeutic efficacy of DSS in HF rats and the protection of gut barrier were assessed. Then, 16S rRNA gene sequencing and untargeted fecal metabolomics preliminarily explored the mechanism of DSS in treating HF, and identified different microbiota and metabolic pathways. Finally, targeted metabolomics and RT-qPCR were used to further validate the mechanism of DSS for HF based on the metabolism of SCFAs and BAs. RESULTS: After 8 weeks of administration, DSS significantly reduced the degree of HF. In addition, DSS alleviated inflammation in the ileum and reduced the levels of LPS and D-lactate. Furthermore, DSS altered the structure of gut microbiota, especially Veillonella, Romboutsia, Monoglobus, Parabacteroides, norank_f_Coriobacteriales_Incertae_Sedis. These bacteria have been linked to the production of SCFAs and the metabolism of BAs. Untargeted metabolomics suggested that DSS may play a role via BAs metabolism. Subsequently, targeted metabolomics and RT-qPCR further confirmed the key role of DSS in increasing SCFAs levels and regulating BAs metabolism. CONCLUSIONS: DSS can alleviate CCl4-induced HF and protect the gut barrier. DSS may exert its beneficial effects on HF by affecting the gut microbiota and its metabolites (SCFAs, BAs).

Incorporating carbon sequestration into lake management: A potential perspective on climate change.

Exploring the carbon sequestration capacity of water ecosystems would contribute to coping with climate change. This study conducted an integrated method framework to achieve an improved understanding of the relationship between carbon sequestration and lake ecosystem components, as well as provide a new perspective on climate change for policymakers. The vertically generalized production model revealed the carbon sequestration capacity of lakes. The hierarchical linear model identified the cross-scale factors affecting phytoplankton. Then a developed multi-agents-based model with scenario analysis provided adaptive management strategies for carbon sequestration. Furthermore, we applied the integrated framework in the 63 polluted lakes of Wuhan. The results showed that the average carbon sequestration per unit area was at 0.87 kgC·m-2·a-1, which was greater than that of the ocean and forest ecosystems, indicating that the lakes had a potential capacity for carbon sequestration. Total phosphorus had the strongest effect on the Chl-a (chlorophyll a) concentration (fixed effect (γ) =6.82, P < 0.1), followed by total nitrogen (γ = 6.38, P < 0.05), Rotifer biomass (γ = 1.95, P < 0.01) and water temperature (γ = 1.27, P < 0.05). These results indicated that the bottom-up effect of chemical factors on phytoplankton was greater than the top-down effect of zooplankton. The proportion of grassland at the whole-lakes level would have a negative synergistic impact on the Chl-a with changing the micro water temperature at the part-lakes level (γ = -46.64, P < 0.05). There was no significant interaction effect between land cover change and total nitrogen (phosphorus) on the Chl-a. Therefore, we could indirectly confirm that point source pollution emissions would synergistically affect the Chl-a and carbon sequestration along with the effects of physical-chemical conditions. The coordinated proportional control of nitrogen and phosphorus and the artificial controlling biomass of zooplankton-feeding fish were proposed to improve carbon sequestration and water quality for lake management.

Impact of clogging on accumulation and stability of phosphorus in the subsurface flow constructed wetland.

Substrate clogging is one of the major operation challenges of subsurface flow constructed wetlands (SSF-CWs). And the phosphorus (P) removal performance and stability of P accumulation of SSF-CWs would be varied with the development of substrate clogging. In this study, three horizontal SSF-CWs microcosms with different clogging degrees were conducted to explore the mechanism of P accumulation behavior influenced by substrate clogging. Increase in clogging degree resulted in hydraulic retention time (HRT) diminution and adsorption sites increase, which jointly led to reduced P removal efficiency at low clogging degree (L-CW), however, higher P removal efficiency was obtained as adsorption sites increase offset HRT diminution at high clogging degree (H-CW). Substrate adsorption was the primary removal pathway in all SSF-CW systems. It accounted for 77.86 ± 2.63% of the P input in the H-CW, significantly higher than the control (60.08 ± 4.79%). This was attributed to a higher proportion of Fe/Al-P accumulated on the substrate of H-CW, since clogging aggravated the anaerobic condition and promoted the generation of Fe ions. The increase in clogging degree also elevated the release risk of the accrued P in SSF-CWs, since Fe/Al-P was considered bioavailable and readily released under environmental disturbance. The obtained results provide new insights into the P transport and transformation in SSF-CWs and would be helpful to optimize substrate clogging management.

Investigation of the therapeutic effect of Shaoyao Gancao decoction on CCL4 -induced liver injury in rats by metabolomic analysis.

Shaoyao Gancao decoction (SGD) is a famous Chinese traditional prescription for treating liver injury. In this research, we investigated the therapeutic effects of SGD on liver injury and its metabolic mechanisms using 1 H NMR and UPLC-MS. Serum biochemical indicators and histopathological methods were used to determine the mechanism of action of SGD in treating liver injury. An orthogonal partial least squares discriminant analysis method was used to screen potential metabolic markers, and the MetaboAnalyst and KEGG PATHWAY databases were used to find relevant metabolic pathways. A total of 26 significant metabolites were identified with significant changes in their abundance levels, and these metabolites are involved in many metabolic pathways such as amino acid and lipid metabolism. The changes in biomarker levels reveal the therapeutic effect of SGD on liver injury, which is of great significance to speculate on possible metabolic mechanisms.

Rapid characterization of the chemical constituents of Sanhua decoction by UHPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry.

Sanhua decoction, a famous Chinese herbal formula has been widely used for the treatment of stroke. In our study, a rapid, swift and straightforward analytical method with the help of UHPLC-FT-ICR-MS/MS was successfully developed for the first time to separate and identify the chemical constituents of Sanhua decoction. Chromatography was performed on a Universal XB C18 column (150 mm × 2.1 mm, 1.8 µm) using a mobile phase containing 0.1% formic acid-water (A) and acetonitrile (B). A total of 137 compounds in Sanhua decoction were identified or tentatively characterized. The findings revealed the fact that Sanhua decoction mainly contains flavonoids (in Aurantii fructus immaturus and Rheum palmatum L.), anthraquinones (in Rheum palmatum L.), coumarins (in Notopterygii Rhizoma Et Radix), phenylpropanoid glycosides, alkaloids and lignans (in Magnoliae Officmalis Cortex), which made up the key ingredients existing in Sanhua decoction. This study is hoped to be meaningful for the characterization of components in other traditional Chinese medicines, and lay the foundation for research on the pharmacology of Sanhua decoction.

Rapid characterization of chemical constituents of Shaoyao Gancao decoction using UHPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry.

Shaoyao Gancao decoction (SGD), a well-known Chinese herbal formula, has been used to treat liver injury for a long time. In this study, chemical profiles of SGD were identified using ultra high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS/MS). Liquid chromatography was performed on a C18 column (150 mm × 2.1 mm, 1.8 µm); the mobile phase comprised 0.1% formic acid (A) and acetonitrile (B). We then characterized 73 chemical compounds; the primary constituents in SGD included phenols and monoterpenes (in Paeoniae Radix Alba), triterpene saponins, and flavonoids (in Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle). Thus, this study provides a basis for further study on SGD and is expected to be useful for rapidly characterizing constituents in other traditional Chinese herbal formulations.

Are mindfulness and self-efficacy related to presenteeism among primary medical staff: A cross-sectional study.

OBJECTIVES: In ensuring public welfare with primary medical and health services, the primary medical staff faces new tasks. Increasing workload, and therefore degrees of stress and burnout, can influence job satisfaction and lead to presenteeism, which is defined as the appearance to be on the job but not actually working. The purpose of this study is to investigate the current working situation and the relationship between presenteeism and mindfulness of primary medical staff and determine the mediating effect of self-efficacy on this relationship. METHOD: A cross-sectional survey was performed with 580 primary medical staff from 9 hospitals in Shaanxi province, northwest China. Presenteeism, mindfulness, and self-efficacy were measured by using a general information questionnaire, the Five-Facet Mindfulness Questionnaire, the General Self-Efficacy Scale, and the Stanford Presenteeism Scale. Mediating effect was analyzed by a series of hierarchical multiple regressions. RESULTS: A high level of presenteeism was found among 47.4% of the study participants. Presenteeism was negatively correlated with mindfulness(r = -0.409, P < 0.001) and self-efficacy(r = -0.678, P < 0.001). A positive correlation was found between mindfulness and self-efficacy(r = 0.584, P < 0.001). When controlling for self-efficacy (ß = -0.018, P > 0.05), the association was insignificant between presenteeism and mindfulness. CONCLUSION: The results identified the effect of mindfulness on presenteeism of primary medical staff is realized through self-efficacy,which also suggested to enhance self-efficacy on center location when developing management strategies for mental health education or training among primary medical staff.

The Efficacy of Eye Movement Desensitization and Reprocessing in Children and Adults Who Have Experienced Complex Childhood Trauma: A Systematic Review of Randomized Controlled Trials.

Background: Survivors of complex childhood trauma (CT) such as sexual abuse show poorer outcomes compared to single event trauma survivors. A growing number of studies investigate Eye Movement Desensitization and Reprocessing (EMDR) treatment for posttraumatic stress disorder (PTSD), but no systematic reviews have focused on EMDR treatment for CT as an intervention for both adults and children. This study therefore systematically reviewed all randomized controlled trials (RCTs) evaluating the effect of EMDR on PTSD symptoms in adults and children exposed to CT. Methods: Databases including PubMed, Web of Science, and PsycINFO were searched in October 2017. Randomized controlled trials which recruited adult and children with experience of CT, which compared EMDR to alternative treatments or control conditions, and which measured PTSD symptoms were included. Study methodology quality was evaluated with Platinum Standard scale. Results: Six eligible RCTs of 251 participants were included in this systematic review. The results indicated that EMDR was associated with reductions in PTSD symptoms, depression and/or anxiety both post-treatment and at follow-up compared with all other alternative therapies (cognitive behavior therapy, individual/group therapy and fluoxetine) and control treatment (pill placebo, active listening, EMDR delayed treatment, and treatment as usual). However, studies suffered from significant heterogeneity in study populations, length of EMDR treatment, length of follow-up, comparison groups, and outcome measures. One study had a high risk of bias. Discussion: This systematic review suggests that there is growing evidence to support the clinical efficacy of EMDR in treating CT in both children and adults. However, conclusions are limited by the small number of heterogenous trials. Further RCTs with standardized methodologies, as well as studies addressing real world challenges in treating CT are required.

Influence of light and temperature on the development and denitrification potential of periphytic biofilms.

Periphytic biofilms are microbial aggregates commonly present in submerged aquatic environments and play a significant role in nutrient cycling. In recent years, utilization of natural periphytic biofilms in wastewater treatment and water restoration attracts growing research interests. Light and temperature are two important environmental factors known to affect the development of periphytic biofilms and can be manipulated for the regulation of the biofilm properties. In this work, effects of light and temperature on the development and function (denitrification potential) of periphytic biofilms were investigated using a microcosm experiment. Results showed that thicker periphytic biofilms with higher Chlorophyll a, extracellular polymeric substances (EPS), and total phosphorus contents were developed under higher temperature. Whereas, biomass accumulation was more rapid for periphytic biofilms under higher irradiance. The denitrification potential rate was negatively associated with irradiance, which can be linked to the influence of irradiance on biofilm structure and microbial composition. A relatively lower irradiance is recommended when using periphytic biofilms in nitrogen removal from wastewater.

Floral traits influence pollen vectors' choices in higher elevation communities in the Himalaya-Hengduan Mountains.

BACKGROUND: How floral traits and community composition influence plant specialization is poorly understood and the existing evidence is restricted to regions where plant diversity is low. Here, we assessed whether plant specialization varied among four species-rich subalpine/alpine communities on the Yulong Mountain, SW China (elevation from 2725 to 3910 m). We analyzed two factors (floral traits and pollen vector community composition: richness and density) to determine the degree of plant specialization across 101 plant species in all four communities. Floral visitors were collected and pollen load analyses were conducted to identify and define pollen vectors. Plant specialization of each species was described by using both pollen vector diversity (Shannon's diversity index) and plant selectiveness (d' index), which reflected how selective a given species was relative to available pollen vectors. RESULTS: Pollen vector diversity tended to be higher in communities at lower elevations, while plant selectiveness was significantly lower in a community with the highest proportion of unspecialized flowers (open flowers and clusters of flowers in open inflorescences). In particular, we found that plant species with large and unspecialized flowers attracted a greater diversity of pollen vectors and showed higher selectiveness in their use of pollen vectors. Plant species with large floral displays and high flower abundance were more selective in their exploitation of pollen vectors. Moreover, there was a negative relationship between plant selectiveness and pollen vector density. CONCLUSIONS: These findings suggest that flower shape and flower size can increase pollen vector diversity but they also increased plant selectiveness. This indicated that those floral traits that were more attractive to insects increased the diversity of pollen vectors to plants while decreasing overlap among co-blooming plant species for the same pollen vectors. Furthermore, floral traits had a more important impact on the diversity of pollen vectors than the composition of anthophilous insect communities. Plant selectiveness of pollen vectors was strongly influenced by both floral traits and insect community composition. These findings provide a basis for a better understanding of how floral traits and community context shape interactions between flowers and their pollen vectors in species-rich communities.

Screening Active Compounds from Garcinia Species Native to China Reveals Novel Compounds Targeting the STAT/JAK Signaling Pathway.

Natural compounds from medicinal plants are important resources for drug development. In a panel of human tumor cells, we screened a library of the natural products from Garcinia species which have anticancer potential to identify new potential therapeutic leads and discovered that caged xanthones were highly effective at suppressing multiple cancer cell lines. Their anticancer activities mainly depended on apoptosis pathways. For compounds in sensitive cancer line, their mechanisms of mode of action were evaluated. 33-Hydroxyepigambogic acid and 35-hydroxyepigambogic acid exhibited about 1 µM IC50 values against JAK2/JAK3 kinases and less than 1 µM IC50 values against NCI-H1650 cell which autocrined IL-6. Thus these two compounds provided a new antitumor molecular scaffold. Our report describes 33-hydroxyepigambogic acid and 35-hydroxyepigambogic acid that inhibited NCI-H1650 cell growth by suppressing constitutive STAT3 activation via direct inhibition of JAK kinase activity.

Label-free measurements of reaction kinetics using a droplet-based optofluidic device.

Label-free measurements of the reaction kinetics of a small sample volume are essential for efficient drug discovery, requiring methods and systems that are rapid, accurate, and cost-effective. Herein, we present an integrated optofluidic system for label-free characterization of reactions in a nanoliter reagent volume. This system contains a droplet-based microfluidic sampling section and an optical fiber-based spectroscopy detection section. By manipulating droplets containing reagents at certain concentrations at different times, quantifiable measurements via absorption spectroscopy can be made in a simple, sensitive, and high-throughput manner. We have demonstrated our system's capability by performing potency (IC50) assays of an inhibitor in a TEM-1 ß-lactamase (enzyme) and nitrocefin (substrate) system. This integrated platform can potentially provide an automated, label-free, and low-cost method for many other assays of reaction kinetics.

Er:YAG laser versus scaling and root planing as alternative or adjuvant for chronic periodontitis treatment: a systematic review.

AIM: To perform a systematic review to evaluate the erbium-doped: yttrium, aluminium and garnet (Er:YAG) laser versus scaling and root planing (SRP) as alternative or adjuvant for chronic periodontitis treatment. MATERIAL AND METHODS: We performed a literature search using six electronic databases and completed by manual searches up to July 2013. We conducted a meta-analysis as well as heterogeneity, sensitivity, subgroup and power analyses to clarify and validate the pooled results. The 3-, 6- and 12-month clinical outcomes were evaluated. RESULTS: Twelve eligible randomized clinical trials were finally included. Our meta-analysis showed that Er:YAG laser resulted in similar clinical improvements as SRP 3 months postoperatively. For subgroups by laser level, quality of trials and fluorescence feedback device, the results remained consistent. The 6- and 12-month observations between Er:YaG laser and SRP demonstrated no difference but inconclusive, due to large heterogeneity. The advantage of Er:YAG laser adjuvant to SRP for periodontitis treatment was not significant. CONCLUSIONS: This systematic review indicated that the clinical efficacy of Er:YAG laser was similar to SRP 3 months postoperatively. The clinical benefits of Er:YAG laser as adjuvant to SRP was still lacking. Since Er:YAG laser has certain advantages, it could be expected to be a novel short-term alternative choice for chronic periodontitis.

In vitro and in vivo anti-cancer activity of formononetin on human cervical cancer cell line HeLa.

Worldwide, cervical cancer (CC) is the third most common malignancy in women, and it remains a leading cause of cancer-related death of women. Genomic studies indicate that phosphoinositide 3-kinase (PI3K)/AKT signaling is one of the most frequently deregulated pathways in several human cancers, including CC. This signaling pathway has an important role in cancer cell proliferation, survival, motility, and metabolism, and therefore could be an attractive therapeutic target. In a previous study, we used a sensitive and high-speed homogeneous assay for the detection of kinase activity and for screening of PI3K/AKT signaling inhibitors in a high-throughput screening (HTS) format and then obtain formononetin, as an O-methylated isoflavone existed in a number of plants and herbs like Astragalus membranaceus. We showed that formononetin inhibited the phosphorylation of AKT and induced the apoptosis of CC cell line HeLa in a dose-dependent manner. Furthermore, formononetin suppressed xenograft tumor growth in nude mice. Our results indicated that formononetin may be used as an anti-cancer drug for cervical cancer in the future.