Daily koumiss has positive regulatory effects on blood lipids and immune system: A metabolomics study.

Koumiss, a traditional Mongolian beverage, is believed to possess high nutritional value and potential medical benefits. However, there is a lack of comprehensive research on its potential impact on the human body. Metabolomics, as a sensitive approach in systems biology, offers a new avenue for studying the overall effects of koumiss. In this work, metabolomics was utilized to identify potential biomarkers and pathways associated with koumiss using UPLC-MS detection, pattern recognition analysis, pathway enrichment, network pharmacology. The findings indicated that koumiss exerts a beneficial regulatory influence on lipid metabolism, neurotransmitters, hormones, phospholipids and arachidonic acid metabolism, besides up regulating the content of nutrients. It could reduce the risks of dyslipidemia and inflammatory responses. This study confirmed the benign regulatory effect of koumiss on normal organism from the perspective of endogenous metabolites, and provided objective support for the promotion and application of this ethnic food.

Tangeretin alleviates inflammation and oxidative response induced by spinal cord injury by activating the Sesn2/Keap1/Nrf2 pathway.

Spinal cord injury (SCI) is a severe disabling disease that is characterized by inflammation and oxidative reactions. Tangeretin has been shown to possess significant antioxidant and anti-inflammatory activities. The Keap1/Nrf2 pathway, downstream of the Sesn2 gene, is involved in regulating the inflammation and oxidative response. The main objective of this study was to investigate the effect of tangeretin on SCI and its possible mechanism through cell and animal models. A T9 clamp injury was used for the mouse model and the LPS-induced stimulation of BV-2 cells was used for the cell model. The improvement of motor function after SCI was assessed by open field, swimming, and footprint experiments. The morphological characteristics of mouse spinal cord tissue and the levels of INOS, Sesn2, TNF-α, Keap1, Nrf2, IL-10, and reactive oxygen species (ROS) in vivo and in vitro were measured by several methods including western blotting, qPCR, immunofluorescence, HE, and Nissl staining. In vivo data showed that tangeretin can improve motor function recovery and reduce neuron loss and injury size in mice with SCI. Simultaneously, the in vitro findings suggested that treatment of BV-2 cells with tangeretin after LPS stimulation reduced the production of inflammatory factors and ROS, and could convert BV-2 cells from the M1 to the M2 type. Furthermore, Sesn2 knockout suppressed Keap1/Nrf2, inflammatory factors, ROS levels, and the M1 to M2 transition. Tangeretin can alleviate the inflammation and oxidative response induced by SCI by activating the Sesn2/Keap1/Nrf2 pathway.

Neuroprotective effects of Anshen Bunao Syrup on cognitive dysfunction in Alzheimer's disease rat models.

Alzheimer's disease (AD) presents a significant challenge due to its prevalence and lack of cure, driving the quest for effective treatments. Anshen Bunao Syrup, a traditional Chinese medicine known for its neuroprotective properties, shows promise in addressing this need. However, understanding its precise mechanisms in AD remains elusive. This study aimed to investigate Anshen Bunao Syrup's therapeutic potential in AD treatment using a scopolamine-induced AD rat model. Assessments included novel-object recognition and Morris water maze tasks to evaluate spatial learning and memory, alongside Nissl staining and ELISA analyses for neuronal damage and biomarker levels. Results demonstrated that Anshen Bunao Syrup effectively mitigated cognitive dysfunction by inhibiting amyloid-ß and phosphorylation Tau aggregation, thereby reducing neuronal damage. Metabolomics profiling of rats cortex revealed alterations in key metabolites implicated in tryptophan and fatty acid metabolism pathways, suggesting a role in the therapeutic effects of Anshen Bunao Syrup. Additionally, ELISA and correlation analyses indicated attenuation of oxidative stress and immune response through metabolic remodeling. In conclusion, this study provides compelling evidence for the neuroprotective effects of Anshen Bunao Syrup in AD models, shedding light on its potential as a therapeutic agent for AD prevention and treatment.

Mertk Reduces Blood-Spinal Cord Barrier Permeability Through the Rhoa/Rock1/P-MLC Pathway After Spinal Cord Injury.

Disruption of the blood-spinal cord barrier (BSCB) is a critical event in the secondary injury following spinal cord injury (SCI). Mertk has been reported to play an important role in regulating inflammation and cytoskeletal dynamics. However, the specific involvement of Mertk in BSCB remains elusive. Here, we demonstrated a distinct role of Mertk in the repair of BSCB. Mertk expression is decreased in endothelial cells following SCI. Overexpression of Mertk upregulated tight junction proteins (TJs), reducing BSCB permeability and subsequently inhibiting inflammation and apoptosis. Ultimately, this led to enhanced neural regeneration and functional recovery. Further experiments revealed that the RhoA/Rock1/P-MLC pathway plays a key role in the effects of Mertk. These findings highlight the role of Mertk in promoting SCI recovery through its ability to mitigate BSCB permeability and may provide potential targets for SCI repair.

The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy.

Intervertebral disc degeneration (IVDD) is an aging disease that results in a low quality of life and heavy socioeconomic burden. The mitochondrial unfolded protein response (UPRmt) take part in various aging-related diseases. Our research intents to explore the role and underlying mechanism of UPRmt in IVDD. Nucleus pulposus (NP) cells were exposed to IL-1ß and nicotinamide riboside (NR) served as UPRmt inducer to treat NP cells. Detection of ATP, NAD + and NADH were used to determine the function of mitochondria. MRI, Safranin O-fast green and Immunohistochemical examination were used to determine the degree of IVDD in vivo. In this study, we discovered that UPRmt was increased markedly in the NP cells of human IVDD tissues than in healthy controls. In vitro, UPRmt and mitophagy levels were promoted in NP cells treated with IL-1ß. Upregulation of UPRmt by NR and Atf5 overexpression inhibited NP cell apoptosis and further improved mitophagy. Silencing of Pink1 reversed the protective effects of NR and inhibited mitophagy induced by the UPRmt. In vivo, NR might attenuate the degree of IDD by activating the UPRmt in rats. In summary, the UPRmt was involved in IVDD by regulating Pink1-induced mitophagy. Mitophagy induced by the UPRmt might be a latent treated target for IVDD.

Deep Learning-Assisted Automated Multidimensional Single Particle Tracking in Living Cells.

The translational and rotational dynamics of anisotropic optical nanoprobes revealed in single particle tracking (SPT) experiments offer molecular-level information about cellular activities. Here, we report an automated high-speed multidimensional SPT system integrated with a deep learning algorithm for tracking the 3D orientation of anisotropic gold nanoparticle probes in living cells with high localization precision (<10 nm) and temporal resolution (0.9 ms), overcoming the limitations of rotational tracking under low signal-to-noise ratio (S/N) conditions. This method can resolve the azimuth (0°-360°) and polar angles (0°-90°) with errors of less than 2° on the experimental and simulated data under S/N of ∼4. Even when the S/N approaches the limit of 1, this method still maintains better robustness and noise resistance than the conventional pattern matching methods. The usefulness of this multidimensional SPT system has been demonstrated with a study of the motions of cargos transported along the microtubules within living cells.

Spectrum-effect relationship study to reveal the pharmacodynamic substances in Flos Puerariae-Semen Hoveniae medicine pair for the treatment of alcohol-induced liver damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Alcoholic liver disease (ALD) is the most serious and irreversible liver damage associated with alcohol consumption. Flos Puerariae and Semen Hoveniae are traditional Chinese medicines (TCM) for dispelling the effects of alcohol. Many studies have shown that the combination of two medicinal materials has the enhanced effect of treating ALD. AIM OF THE STUDY: The aim of this study is to assess the pharmacological effects of Flos Puerariae-Semen Hoveniae medicine pair, to elucidate its action mechanism in the treatment of alcohol-induced BRL-3A cells, and to reveal the active ingredients in the medicine pair that exerted pharmacological effects by spectrum-effect relationship study. MATERIALS AND METHODS: Firstly, MTT assays, ELISA, fluorescence probe analysis, and Western blot were employed to study the underlying mechanisms of the medicine pair in alcohol-induced BRL-3A cells by examining pharmacodynamic indexes and related protein expression. Secondly, HPLC method was established for chemical chromatograms of the medicine pair with different ratios and the sample extracted by different solvents. Then, principal component analysis, pearson bivariate correlation analysis and grey relational analysis were applied for development of the spectrum-effect correlation between pharmacodynamic indexes and HPLC chromatograms. Moreover, prototype components and their metabolites in vivo were identified by the HPLC-MS method. RESULTS: Flos Puerariae-Semen Hoveniae medicine pair remarkably increased cell viability, decreased the activity of ALT, AST, TC and TG, reduced the generation of TNF-α, IL-1ß, IL-6, MDA and ROS, increased the activity of SOD and GSH-Px, reduced protein expression of CYP2E1, compared with alcohol-induced BRL-3A cells. The medicine pair modulated the PI3K/AKT/mTOR signaling pathways by up-regulating the levels of phospho-PI3K, phospho-AKT and phospho-mTOR. Also, the results of the spectrum-effect relationship study showed that P1 (chlorogenic acid), P3 (daidzin), P4 (6″-O-xylosyl-glycitin), P5 (glycitin), P6 (unknown), P7 (unknown), P9 (unknown), P10 (6″-O-xylosyl-tectoridin), P12 (tectoridin) and P23 (unknown) can be considered as the main components of the medicine pair in the treatment of ALD. Furthermore, 6″-O-xylosyl-tectoridin, tectoridin, daidzin, 6″-O-xylosyl-glycitin and glycitin can be absorbed into the blood and showed clear metabolic and excretion behaviors in rats. CONCLUSION: In this study, the hepatoprotective effects and the pharmacology mechanism of Flos Puerariae-Semen Hoveniae medicine pair in alcohol-induced BRL-3A cells were initially investigated and revealed. Through the spectrum-effect relationship study, the potential pharmacodynamic constituents such as daidzin, 6″-O-xylosyl-glycitin, 6″-O-xylosyl-tectoridin, glycitin, and tectoridin exert pharmacological effects on alcohol-induced oxidative stress and inflammation by modulating the PI3K/AKT/mTOR signaling pathways. This study provided experimental basis and data support for revealing the pharmacodynamic substance basis and pharmacology mechanism in the treatment of ALD. Moreover, it provides a robust mean of exploring the primary effective components responsible for the bioactivity of complicated TCM.

Investigation on the mechanism of Ginkgo Folium in the treatment of Non-alcoholic Fatty Liver Disease by strategy of network pharmacology and molecular docking.

BACKGROUND: Ginkgo Folium has a favorable effect on non-alcoholic fatty live disease (NAFLD), but its mechanism remains unclear. OBJECTIVE: The aim of this study is to reveal the underlying mechanism of Ginkgo Folium in the treatment of NAFLD. METHODS: Ingredients of Ginkgo Folium and ingredients-related genes were collected from TCMSP database and SwissTargetPrediction website, respectively. Genecards database was used to obtain NAFLD-related genes. Next, the protein-protein interaction network and key ingredients-genes network were constructed via Cytoscape3.7.0. Based on the Metascape website, gene ontology function analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were carried out for key genes. Finally, molecular docking was performed to present the interaction between components and genes using AutoDock Vina 1.1.2. RESULTS: Eighteen active ingredients and 10 target genes were screened from Ginkgo Folium. AKT1, TNF, EGFR, PTGS2, MAPK8, PPAγ, APP, ESR1, HIFα and PPAα were considered as potential therapeutic targets. These target genes were mainly enriched in insulin resistance, HIF-1, adipocytokine and AMPK signaling pathways. Molecular docking results suggested that Ginkgo Folium active ingredients including luteolin-4'-glucoside, sesamin, luteolin, chryseriol, isorhamnetin and laricitrin showed strong binding capacities with AKT1. CONCLUSION: The study showed that multi-components in Ginkgo Folium interacted with AKT1 and regulated AKT-AMPK/HIF pathway to alleviate NAFLD. Our findings provided an essential role and basis for new anti-NAFLD drug discovery and further research on Ginkgo Folium.

Chuanzhitongluo capsule ameliorates microcirculatory dysfunction in rats: Efficacy evaluation and metabolic profiles.

Background: Ischemic stroke is a leading cause of mortality and disability worldwide. Microcirculatory dysfunction is the foremost hindrance for a good clinical prognosis in ischemic stroke patients. Clinical researches show that Chuanzhitongluo capsule (CZTL) has a curative effect during the recovery period of ischemic stroke, which contributes to a good prognosis. However, it is not known whether CZTL treats ischemic stroke by ameliorating microcirculation dysfunction. Objective: In this study, we investigated the influence of CZTL on microcirculation and its underlying mechanism. Methods: A rat model of acute microcirculatory dysfunction was established by stimuli of adrenaline and ice water. The microcirculatory damage in model rats and the efficacy of CZTL were assessed by detecting laser speckle contrast imaging, coagulation function, hemorheology, vasomotor factor and microcirculation function. The potential mechanism of CZTL action was explored by the untargeted metabolomic analysis based on ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Results: Laser speckle contrast imaging showed that model rats suffered low perfusion in ears, feet and tails, and CZTL treatment increased microcirculatory blood flow. Coagulation function detection results showed that CZTL diminished the reduction of thrombin time, prothrombin time, activated partial thromboplastin time and the elevated fibrinogen level caused by acute microcirculatory dysfunction. Furthermore, CZTL could recover the increased blood viscosity as well as the abnormal vasomotor and microcirculation function in rats with acute microcirculatory dysfunction. Metabolomics analysis indicated that CZTL might regulate sphingolipid metabolism and arachidonic acid metabolism to exert protective effects on microcirculation. Conclusion: These results elucidated that CZTL was highly effective against microcirculatory dysfunction and its potential mechanisms related with the modulation of sphingolipid and arachidonic acid metabolic pathways. The present study provided a new perspective on the clinical application of CZTL, and it contribute to explore novel therapeutic drug against microcirculatory dysfunction.

Network pharmacological investigation into the mechanism of Kaixinsan powder for the treatment of depression.

Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway).

Metabolomic and Microbial Remodeling by Shanmei Capsule Improves Hyperlipidemia in High Fat Food-Induced Mice.

Hyperlipidemia refers to a chronic disease caused by systemic metabolic disorder, and its pathophysiology is very complex. Shanmei capsule (SM) is a famous preparation with a long tradition of use for anti-hyperlipidemia treatment in China. However, the regulation mechanism of SM on hyperlipidemia has not been elucidated so far. In this study, a combination of UPLC-Q-TOF/MS techniques and 16S rDNA gene sequencing was performed to investigate the effects of SM treatment on plasma metabolism-mediated change and intestinal homeostasis. The results indicated that SM potently ameliorated high-fat diet-induced glucose and lipid metabolic disorders and reduced the histopathological injury. Pathway analysis indicated that alterations of differential metabolites were mainly involved in glycerophospholipid metabolism, linolenic acid metabolism, α-linoleic acid metabolism, and arachidonic acid metabolism. These changes were accompanied by a significant perturbation of intestinal microbiota characterized by marked increased microbial richness and changed microbiota composition. There were many genera illustrating strong correlations with hyperlipidemia-related markers (e.g., weight gains, GLU, and total cholesterol), including the Lachnospiraceae NK4A136 group and the Lachnospiraceae NK4B4 group. Overall, this study initially confirmed that hyperlipidemia is associated with metabolic disturbance and intestinal microbiota disorders, and SM can be employed to help decrease hyperlipidemia risk, including improving the abnormal metabolic profile and maintaining the gut microbial environment.

Integrated metabolomics and 16S rDNA sequencing to investigate the mechanism of immune-enhancing effect of health Tonic oral liquid.

Health Tonic oral liquid (HT) is a popular functional food in China and is used to enhance host immune response. However, its mechanisms of action are still poorly understood. In this work, we combined ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) serum metabolomics with 16S rDNA sequencing to evaluate the effects of HT on metabolomics profiling and microbial community signatures. Short-chain fatty acids (SCFAs) contents in fecal were quantified through gas chromatography-mass spectrometry (GC-MS). Results indicated that HT use leads to a significant increase in IgG, IgM and IgA. Thirty-four metabolites were identified and quantified using metabolomics, most were aromatic amino acids and metabolites involved in glucose metabolism. HT intervention significantly increased the abundance of Alloprevotella, which may contribute to intestinal barrier integrity and inflammatory response inhabitation. Most SCFAs were highly expressed following HT intake. In summary, HT use maintains glucose and lipid metabolism balance, promotes high expressions of beneficial bacteria, and exerts promising immunomodulatory effects.

Ultrasensitive split-type electrochemical sensing platform for sensitive determination of organophosphorus pesticides based on MnO2 nanoflower-electron mediator as a signal transduction system.

Organophosphorus pesticides (OPs) are extensively used worldwide as agrochemicals; however, excess use may threaten the health of humans. Thus, it is an urgent need to develop a sensitive method for determination of OPs. Herein, a simple and sensitive split-type electrochemical method was developed by using MnO2 nanoflower-electron mediator as a signal transduction element. The MnO2 nanoflower-electron mediator was synthesized and shows an excellent electrochemical signal attributed to the high specific surface area of MnO2 nanoflower. Meanwhile, the inhibition of OPs on butyrylcholinesterase (BChE) was carried out in the homogeneous system. In the absence of target molecule, a large number of thiocholines (TCh) were yielded from hydrolysis of acetylthiocholine (ATCh) by BChE. The MnO2 nanoflower was cracked, and subsequently, multiple electron mediator molecules were released from the platform after treated with TCh, thus decreasing the electrochemical response. Furthermore, the inhibition of OPs on BChE resulted in the reduced generation of TCh, thus inducing the recovery of electrochemical signal. Under the optimal experimental, dichlorvos can be detected in a wide range of 10-6-10-10 M, with a detection limit of 3 × 10-10 M. Moreover, the assay was successfully used to analyze dichlorvos in cucumber juice and pear juice, showing a great promising potential for detecting organophosphorus pesticides in complex samples. Graphical abstract In this assay, a split-type electrochemical biosensor was proposed for the ultrasensitive determination of organophosphorus pesticides based on the MnO2 nanoflower-electron mediator as an electrochemical signal component.

Rolling circle amplification promoted magneto-controlled photoelectrochemical biosensor for organophosphorus pesticides based on dissolution of core-shell MnO2 nanoflower@CdS mediated by butyrylcholinesterase.

A photoelectrochemical (PEC) aptasensing platform is devised for sensitive detection of an organophosphorus pesticide based on dissolution of core-shell MnO2 nanoflower@CdS (MnO2 NF@CdS) by thiocholine (TCh). TCH is produced from the butyrylcholinesterase-acetylthiocholine system, accompanied by target-triggered rolling circle amplification (RCA). The core-shell MnO2 NF@CdS with excellent PEC performance was synthesized and employed as a photo-sensing platform. The target was detected on a functionalized magnetic probe with the corresponding aptamer. Upon malathion introduction, the aptamer was detached from the magnetic beads, while capture DNA (cDNA, with primer fragment) remained on the beads. The primer fragment in cDNA can trigger the RCA reaction to form a long single-stranded DNA (ssDNA). Furthermore, a large number of butyrylcholinesterase (BChE) were assembled on the long ssDNA strands through the hybridization with the S2-Au-BChE probe. Thereafter, TCh generated from hydrolysis of ATCh by BChE can reduce MnO2 NF (core) to Mn2+ and release the CdS nanoparticles (shell) from the platform electrode, significantly enhancing the PEC signal. Under optimal conditions, the proposed aptasensor exhibited high sensitivity for malathion with a low detection limit of 0.68 pg mL-1. Meanwhile, it also presents outstanding specificity, reproducibility, and stability. Importantly, the sensing platform provides a new concept for detection of pesticide. Graphical abstract Herein, this work devised a photoelectrochemical (PEC) aptasensing platform for sensitive detection of organophosphorus pesticide based on dissolution of core-shell MnO2 nanoflower@CdS (MnO2 NF@CdS) by the as-produced thiocholine (TCh) from the butyrylcholinesterase-acetylthiocholine system, accompanying with the target-triggered rolling circle amplification (RCA).

A clinical metabolomics-based biomarker signature as an approach for early diagnosis of gastric cardia adenocarcinoma.

Gastric cardia adenocarcinoma (GCA) has a high mortality rate worldwide; however, current early diagnostic methods lack efficacy. Therefore, the aim of the present study was to identify potential biomarkers for the early diagnosis of GCA. Global metabolic profiles were obtained from plasma samples collected from 21 patients with GCA and 48 healthy controls using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry. The orthogonal partial least squares discrimination analysis model was applied to distinguish patients with GCA from healthy controls and to identify potential biomarkers. Metabolic pathway analysis was performed using MetaboAnalyst (version 4.0) and revealed that 'glycerophospholipid metabolism', 'linoleic acid metabolism', 'fatty acid biosynthesis' and 'primary bile acid biosynthesis' were significantly associated with GCA. In addition, an early diagnostic model for GCA was established based on the relative levels of four key biomarkers, including phosphorylcholine, glycocholic acid, L-acetylcarnitine and arachidonic acid. The area under the receiver operating characteristic curve revealed that the diagnostic model had a sensitivity and specificity of 0.977 and 0.952, respectively. The present study demonstrated that metabolomics may aid the identification of the mechanisms underlying the pathogenesis of GCA. In addition, the proposed diagnostic method may serve as a promising approach for the early diagnosis of GCA.

Pregnancy-specific anxiety and elective cesarean section in primiparas: A cohort study in China.

The purpose of this study was to investigate the association between pregnancy-specific anxiety and elective cesarean section, and identify the critical period in which pregnancy-specific anxiety will affect the elective cesarean section. Primiparous women in the 1st trimester of pregnancy were invited to participate in the cohort. General information on maternal socio-demographic characteristics and environmental exposure were collected using questionnaires. Pregnancy-specific anxiety was assessed by using pregnancy-specific anxiety questionnaire in the 1st, 2nd and 3rd trimester, respectively. Delivery modes and pregnancy complications were abstracted from medical notes. Structural equation modeling (SEM) was adopted to examine the relationship between pregnancy-specific anxiety and elective cesarean section. Results indicated the overall elective cesarean section rate in this study was 45%. Among 1 874 pregnant women, 30.9% women experienced anxiety at least once during pregnancy, and 6.9% women suffered from anxiety in all three trimesters. Anxiety in the 2nd trimester was a significant predictor for elective cesarean section. Young maternal age and low educational level had indirect effects on women's choice of elective caesarean section through affecting pregnancy-specific anxiety. More attention should be paid to maternal psychological problems, and professional counseling needs to be strengthened to protect women from pregnancy-specific anxiety.

Elective caesarean delivery and offspring's cognitive impairment: Implications of methylation alteration in hippocampus glucocorticoid signaling genes.

Elective caesarean delivery (CD) is an atypical early-life stressful event towards infants. It can pose a long-term effect to children's development by programming hypothalamus-pituitary-adrenal axis. However, the effect of elective CD on offspring's long-term cognitive function and the potential molecular mechanism remains unknown. In this study, by establishing CD mice model, we found that mice born with CD had lower corticosterone level at birth compared with those born by vaginal delivery (VD). Impairment in learning and memory was observed in CD offspring in adolescence, while the effect did not persist in the adulthood. In hippocampus, the expression of glucocorticoid receptor gene (Nr3c1) and FK506 binding protein gene 5 (Fkbp5) was higher in CD offspring in all postnatal time points. In hippocampus, the average methylation level at nerve growth factor-inducible protein A (NGFI-A) binding sites in exon 17 of Nr3c1, and the methylation in intron 1, intron 5 of Fkbp5 were all lower in CD offspring at infancy. Our data implicated that elective CD will cause delayed but non-permanent cognitive impairment in offspring. Insufficient glucocorticoid function caused by elective CD may bridge the association between this operative delivery mode and offspring's cognitive impairment. Methylation alterations in key regions of glucocorticoid signaling genes may partially explain the function of glucocorticoid related with elective CD.

Three new alkaloids from Xylopia vielana and their antiinflammatory activities.

Three new aporphine alkaloids, xylopialoids A-C (1-3), along with three known aporphine alkioids (4-6) and three other known compounds (7-9) were isolated from the roots of Xylopia vielana. Among these three new aporphine alkaloids, xylopialoid C (3) showed a special carbamido group directly connected to the nitrogen. The chemical structures of these nine compounds were determined by a combination of 1D and 2D NMR, MS, CD spectrum and Cu Kα X-ray crystallographic analyses. All these six alkaloids were firstly tested for the inhibitory activities against the production of NO in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Among these compounds, 4 showed a potential inhibitory activity against the production of nitric oxide with IC50 value of 1.39 µM.

Placenta response of inflammation and oxidative stress in low-risk term childbirth: the implication of delivery mode.

BACKGROUND: Caesarean delivery rate is increasing gradually in China and there is no doubt that delivery mode is closely associated with the maternal health and infant development.This study examined the independent effect of delivery mode on placenta inflammation response and oxidative stress response. METHODS: A total of 3474 pregnant women recruited in Ma'anshan Birth Cohort Study were the initial study population. Data on maternal socio-demographic characteristics and pre-pregnancy BMI were collected at their 1st antenatal checkups. Pregnancy-specific anxiety was assessed during the three trimesters of pregnancy. Common pregnant complications were monitored in the whole pregnancy period. Delivery modes, as well as newborn characteristics were abstracted from medical records. Delivery modes included vaginal deliveries (VD), caesarean delivery with medical indications (CDMI), caesarean delivery on maternal request (CDMR) and urgent cesarean delivery (UCD). Placentas were collected during childbirth. The mRNA expression of IL-1ß, TNF-a, IL-6, IFN-γ, IL-4, IL-10, IL-8, and HO-1 were assessed in the final sample of 1978 low-risk women with singleton term-births. RESULTS: The overall rate of caesarean delivery (CD) was 50.5% (1650/3265) in singleton term childbirths in this study. Among women who reported definite CD reasons, 56.8%of them chose the surgery without any medical indications.It shows a non-linear relationship between cytokines related with placenta inflammatory response, oxidative stress response and different delivery modes. At high percentiles of IL-1ß, IFN-γ and IL-8, women with CDMR had higher expression levels compared to women with VD. Women with CDMI had higher levels at median percentiles of IL-1ß, IFN-γ and IL-8. Women with CDMR had higher expression compared with VD at high percentiles of IL-6 and HO-1, and women with CDMI had higher levels of these two cytokines at their low percentiles. It is worth noting that at high percentiles, compared with normal delivery, the expression of IL-1ß, IFN-γ, IL-8 and HO-1 have significantly altered in women with CDMR. CONCLUSION: A high overall CD rate was found in this study, and caesarean delivery on maternal request was the major contributor to the high prevalence. Maternal placental oxidative stress and inflammatory response were closely associated with delivery mode. The effect is much amplified at high levels of expression in women who chose CD on maternal request.Such difference needs to be noticed and may have important implications for obstetricians, midwives and other perinatal health care workers.

Synthesis of PS/Ag nanocomposite spheres with catalytic and antibacterial activities.

This paper describes a simple, mild, and environmentally friendly approach to synthesize polystyrene/Ag (PS/Ag) nanocomposite spheres, which makes use of both reducing and stabilizing functions of polyvinylpyrrolidone (PVP) in aqueous media. In this approach, monodisperse polystyrene (PS) spheres, which are used as templates for the synthesis of core-shell nanocomposite spheres, are sulfonated first. Then, [Ag(NH(3))(2)](+) ions are adsorbed onto the surface of the PS template spheres via electrostatic attraction between -SO(3)H groups (grafted on the surface of the PS template spheres) and [Ag(NH(3))(2)](+) ions. [Ag(NH(3))(2)](+) ions are then reduced by and simultaneously protected by PVP. In this way, the PS/Ag nanocomposite spheres in aqueous media are obtained through a so-called one-pot method. Neither additional reducing agents nor toxic organic solvents are utilized during the synthesis process. Furthermore, the coverage degree and the particle size of Ag nanoparticles on PS/Ag nanocomposite spheres is easily tuned by changing the concentration of [Ag(NH(3))(2)](+) ions in aqueous media. Moreover, these PS/Ag nanocomposite spheres can be used as catalyst for the reduction of organic dyes and as antibacterial agents against Salmonella and Escherichia coli. In the present study, these PS/Ag nanocomposite spheres exhibit excellent catalytic properties (both in efficiency and recyclability) for the reduction of organic dyes, and the preliminary antibacterial assays indicate that these PS/Ag nanocomposite spheres also possess extraordinary antibacterial abilities against Salmonella and Escherichia coli.