Clinical rules of Acupoint selection for cancer pain opioid-induced constipation based on journal literature data mining: A systematic review.

Objective: To analyse and summarise the regularity of acupoint selection in the treatment of opioid-induced constipation (OIC) in patients with cancer pain using a data mining technique and provide a reference for clinical practice and more valuable treatment options. Methods: The acupoint prescription database for the treatment of OIC-related cancer pain was established by searching the relevant literature on randomised controlled trials involving acupoint therapy for OIC-related cancer pain in seven major databases, including the China National Knowledge Infrastructure, Wanfang and VIP Chinese scientific journal databases, from database establishment to December 31, 2022. The main therapeutic measures of acupoint prescription, frequency of acupoint use and its subordinate meridians and subordinate sites were then analysed. Through systematic clustering and association rule analysis, the core acupoint prescriptions and most commonly used acupoint compatibility of acupoint therapy for OIC-related cancer pain were obtained. Results: A total of 649 articles were retrieved, with 72 articles included after screening. The treatment measures were found to be mainly acupoint applications involving 28 acupoints, with a total frequency of 234. The three most frequently used acupoints were Shenque, Tianshu and Zusanli. The number of points used in the Foot-Yangming stomach meridian was the highest. Commonly used acupoints were mainly distributed in the abdomen. The compatibility of two commonly used acupoints was obtained through systematic clustering. Through association rule analysis, it was found that in the compatibility of acupoints, the strongest correlation was between Tianshu and Zusanli, and their frequency of application was the highest. Conclusion: Tianshu and Zusanli are the core acupoints for acupoint therapy in the treatment of OIC-related cancer pain, and the Shangjuxu-Zhigou-Zusanli, Qihai-Guanyuan and Zhongwan-Tianshu acupoints exhibit the highest compatibility. This study provides a reference for the clinical acupoint selection programme of acupuncture and moxibustion in the treatment of OIC-related cancer pain.

A nanocomposite hydrogel for co-delivery of multiple anti-biofilm therapeutics to enhance the treatment of bacterial biofilm-related infections.

The characteristics of biofilms have exacerbated the issue of clinical antibiotic resistance, rendering it a pressing challenge in need of resolution. The combination of biofilm-dispersing agents and antibiotics can eliminate biofilms and promote healing synergistically in infected wounds. In this study, we developed a novel nanocomposite hydrogel (NC gel) comprised of the poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG) based bioadhesive nanoparticles (BNPs) and a hydrophilic carboxymethyl chitosan (CS) network. The NC gel was designed to co-deliver two biofilm-dispersing agents (an NO-donor SNO, and an α-amylase Am) and an antibiotic, cefepime (Cef), utilizing a synergistic anti-biofilm mechanism in which Am loosens the matrix structure and NO promotes the release of biofilm bacteria via quorum sensing, and Cef kills bacteria. The drug-loaded NC gel (SNO/BNP/CS@Am-Cef) demonstrated sustained drug release, minimal cytotoxicity, and increased drug-bacterial interactions at the site of infection. When applied to mice infected with methicillin-resistant Staphylococcus aureus (MRSA) biofilms in vivo, SNO/BNP/CS@Am-Cef enhanced biofilm elimination and promoted wound healing compared to traditional antibiotic treatments. Our work demonstrates the feasibility of the co-delivery of biofilm-dispersing agents and antibiotics using the NC gel and presents a promising approach for the polytherapy of bacterial biofilm-related infections.

Discovery of the covalent SARS-CoV-2 Mpro inhibitors from antiviral herbs via integrating target-based high-throughput screening and chemoproteomic approaches.

The main proteases (Mpro ) are highly conserved cysteine-rich proteins that can be covalently modified by numerous natural and synthetic compounds. Herein, we constructed an integrative approach to efficiently discover covalent inhibitors of Mpro from complex herbal matrices. This work begins with biological screening of 60 clinically used antiviral herbal medicines, among which Lonicera japonica Flos (LJF) demonstrated the strongest anti-Mpro effect (IC50 = 37.82 µg/mL). Mass spectrometry (MS)-based chemical analysis and chemoproteomic profiling revealed that LJF extract contains at least 50 constituents, of which 22 exhibited the capability to covalently modify Mpro . We subsequently verified the anti-Mpro effects of these covalent binders. Gallic acid and quercetin were found to potently inhibit severe acute respiratory syndrome coronavirus 2 Mpro in dose- and time- dependent manners, with the IC50 values below 10 µM. The inactivation kinetics, binding affinity and binding mode of gallic acid and quercetin were further characterized by fluorescence resonance energy transfer, surface plasmon resonance, and covalent docking simulations. Overall, this study established a practical approach for efficiently discovering the covalent inhibitors of Mpro from herbal medicines by integrating target-based high-throughput screening and MS-based assays, which would greatly facilitate the discovery of key antiviral constituents from medicinal plants.

PTPN2 copper-sensing rapidly relays copper level fluctuations into EGFR/CREB activation and associated CTR1 transcriptional repression.

Fluxes in human intra- and extracellular copper levels recently garnered attention for roles in cellular signaling, including affecting levels of the signaling molecule cyclic adenosine monophosphate (cAMP). We herein applied an unbiased temporal evaluation of the whole-genome transcriptional activities modulated by fluctuations in copper levels to identify the copper sensor proteins responsible for driving these activities. We found that fluctuations in physiologically-relevant copper levels rapidly modulate EGFR/MAPK/ERK signal transduction and activation of the transcription factor cAMP response element-binding protein (CREB). Both intracellular and extracellular assays support Cu 1+ inhibition of the EGFR-phosphatase PTPN2 (and potentially the homologous PTPN1)-via direct ligation to the PTPN2 active site cysteine side chain-as the underlying mechanism of copper-stimulated EGFR signal transduction activation. Depletion of copper represses this signaling pathway. We additionally show i ) copper supplementation drives transcriptional repression of the copper importer CTR1 and ii ) CREB activity is inversely correlated with CTR1 expression. In summary, our study reveals PTPN2 as a physiological copper sensor and defines a regulatory mechanism linking feedback control of copper-stimulated MAPK/ERK/CREB-signaling and CTR1 expression, thereby uncovering a previously unrecognized link between copper levels and cellular signal transduction.

Chemical profiling and mechanistic studies of Zhi-Shang-Feng granules against influenza virus by high-performance liquid chromatography coupled with Q exactive focus hybrid quadrupole orbitrap high-resolution mass spectrometry in combination with network pharmacology analysis.

Zhi-Shang-Feng Granules are used in the clinical treatment of influenza to relieve headaches, chills and fever, bronchitis, nasal congestion, neuralgia and other symptoms. To decipher the components responsible for therapeutic effects of Zhi-Shang-Feng g ranules against influenza virus, an analytical method based on high-performance liquid chromatography coupled with Q exactive focus hybrid quadrupole orbitrap high resolution mass spectrometry was developed and the chemical profile of Zhi-Shang-Feng granules was characterized. Then, the identified components were used to conduct network pharmacological analysis and determine the potential mechanism of Zhi-Shang-Feng Granules. As a result, 177 compounds were putatively identified through comprehensive analysis by liquid chromatography coupled with high-resolution mass spectrometry, of which 23 compounds were unambiguously confirmed with reference standards. Components in Zhi-Shang-Feng Granules were found to specifically act on different enzymes, G-protein-coupled receptors, ion channels and transporters in the immune, endocrine, nervous, and circulatory systems. The potential mechanism was related to several biological processes, including cell growth and death, pattern recognition receptor signalling, signalling by interleukins, and lipid metabolism. The combination of chemical profile characterization and network construction provided useful insight into the overall chemical composition of Zhi-Shang-Feng granules and revealed their potential anti-infection, anti-inflammatory and immunoregulatory mechanisms against influenza virus infected disease.

Reduction and adsorption of uranium(VI) from aqueous solutions using nanoscale zero-valent manganese.

Nano zero-valent manganese (nZVMn) is theoretically expected to exhibit high reducibility and adsorption capacity, yet its feasibility, performance, and mechanism for reducing and adsorbing hexavalent uranium (U(VI)) from wastewater remain unclear. In this study, nZVMn was prepared via borohydride reduction, and its behaviors about reduction and adsorption of U(VI), as well as the underlying mechanism, were investigated. Results indicated that nZVMn exhibited a maximum U(VI) adsorption capacity of 625.3 mg/g at a pH of 6 and an adsorbent dosage of 1 g/L, and the co-existing ions (K+, Na+, Mg2+, Cd2+, Pb2+, Tl+, Cl-) at studied range had little interference on U(VI) adsorption. Furthermore, nZVMn effectively removed U(VI) from rare-earth ore leachate at a dosage of 1.5 g/L, resulting in a U(VI) concentration of lower than 0.017 mg/L in the effluent. Comparative tests demonstrated the superiority of nZVMn over other manganese oxides (Mn2O3 and Mn3O4). Characterization analyses, including X-ray diffraction and depth profiling X-ray photoelectron spectroscopy, combined with density functional theory calculation revealed that the reaction mechanism of U(VI) using nZVMn involved reduction, surface complexation, hydrolysis precipitation, and electrostatic attraction. This study provides a new alternative for efficient removal of U(VI) from wastewater and improves the understanding of the interaction between nZVMn and U(VI).

Lycium barbarum polysaccharide alleviates dextran sodium sulfate-induced inflammatory bowel disease by regulating M1/M2 macrophage polarization via the STAT1 and STAT6 pathways.

Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal Lycium barbarum L., which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD. To test this hypothesis, the DSS-induced colitis model was established in mice, then the mice were treated with LBP. The results indicated that LBP attenuated the weight loss, colon shortening, disease activity index (DAI), and histopathological scores of colon tissues in colitis mice, suggesting that LBP could protect against IBD. Besides, LBP decreased the number of M1 macrophages and the protein level of Nitric oxide synthase 2(NOS2) as a marker of M1 macrophages and enhanced the number of M2 macrophages and the protein level of Arginase 1(Arg-1) as a marker of M2 macrophages in colon tissues from mice with colitis, suggesting that LBP may protect against IBD by regulating macrophage polarization. Next, the mechanistic studies in RAW264.7 cells showed that LBP inhibited M1-like phenotype by inhibiting the phosphorylation of STAT1, and promoted M2-like phenotype by promoting the phosphorylation of STAT6. Finally, immunofluorescence double-staining results of colon tissues showed that LBP regulated STAT1 and STAT6 pathways in vivo. The results in the study demonstrated that LBP could protect against IBD by regulating macrophage polarization through the STAT1 and STAT6 pathways.

17ß-oestradiol inhibits ferroptosis in the hippocampus by upregulating DHODH and further improves memory decline after ovariectomy.

Ovariectomy (OVX) conducted before the onset of natural menopause is considered to bringing forward and accelerate the process of ageing-associated neurodegeneration. However, the mechanisms underlying memory decline and other cognitive dysfunctions following OVX are unclear. Given that iron accumulates during ageing and after OVX, we hypothesized that excess iron accumulation in the hippocampus would cause ferroptosis-induced increased neuronal degeneration and death associated with memory decline. In the current study, female rats that underwent OVX showed decreased dihydroorotate dehydrogenase (DHODH) expression and reduced performance in the Morris water maze (MWM). We used primary cultured hippocampal cells to explore the ferroptosis resistance-inducing effect of 17ß-oestradiol (E2). The data supported a vital role of DHODH in neuronal ferroptosis. Specifically, E2 alleviated ferroptosis induced by erastin and ferric ammonium citrate (FAC), which can be blocked by brequinar (BQR). Further in vitro studies showed that E2 reduced lipid peroxidation levels and improved the behavioural performance of OVX rats. Our research interprets OVX-related neurodegeneration with respect to ferroptosis, and both our in vivo and in vitro data show that E2 supplementation exerts beneficial antiferroptotic effects by upregulating DHODH. Our data demonstrate the utility of E2 supplementation after OVX and provide a potential target, DHODH, for which hormone therapy has not been available.

Phenolic compounds from the flowers of Rosa hugonis Hemsl. and their neuroprotective effects.

The fragrant flowers of Rosa hugonis Hemsl. Contain abundant valuable rose oil and carotenoids. However, phytochemical investigation of this resource rich in phenolics with neuroprotective activity in vitro has been rarely reported. Purification of the 70% ethanol extracts from the flowers of R. hugonis by various chromatographic methods resulted in the isolation and characterization of five undescribed acylated flavonoid glycosides (Hugonisflavonoid A-E) together with forty known phenolics. The chemical structures of the undescribed compounds were elucidated by extensive analysis of their spectroscopic data and chemical methods. All the isolates were found from R. hugonis for the first time and evaluated for their neuroprotective effects on 6-OHDA induced injury in PC12 cells. Seventeen compounds displayed remarkable protective effects at concentrations of 10 µM. Hugonisflavonoid E can reduce excessive reactive oxygen species and up-regulate mRNA expression levels of superoxide dismutase 1 and catalase. Additionally, hugonisflavonoid E activated the phosphorylated proteins such as PDK1, Akt and GSk-3ß. These findings suggested that R. hugonis could be a potential source for neuroprotective agents.

Cross-Domain Facial Expression Recognition: A Unified Evaluation Benchmark and Adversarial Graph Learning.

Facial expression recognition (FER) has received significant attention in the past decade with witnessed progress, but data inconsistencies among different FER datasets greatly hinder the generalization ability of the models learned on one dataset to another. Recently, a series of cross-domain FER algorithms (CD-FERs) have been extensively developed to address this issue. Although each declares to achieve superior performance, comprehensive and fair comparisons are lacking due to inconsistent choices of the source/target datasets and feature extractors. In this work, we first propose to construct a unified CD-FER evaluation benchmark, in which we re-implement the well-performing CD-FER and recently published general domain adaptation algorithms and ensure that all these algorithms adopt the same source/target datasets and feature extractors for fair CD-FER evaluations. Based on the analysis, we find that most of the current state-of-the-art algorithms use adversarial learning mechanisms that aim to learn holistic domain-invariant features to mitigate domain shifts. However, these algorithms ignore local features, which are more transferable across different datasets and carry more detailed content for fine-grained adaptation. Therefore, we develop a novel adversarial graph representation adaptation (AGRA) framework that integrates graph representation propagation with adversarial learning to realize effective cross-domain holistic-local feature co-adaptation. Specifically, our framework first builds two graphs to correlate holistic and local regions within each domain and across different domains, respectively. Then, it extracts holistic-local features from the input image and uses learnable per-class statistical distributions to initialize the corresponding graph nodes. Finally, two stacked graph convolution networks (GCNs) are adopted to propagate holistic-local features within each domain to explore their interaction and across different domains for holistic-local feature co-adaptation. In this way, the AGRA framework can adaptively learn fine-grained domain-invariant features and thus facilitate cross-domain expression recognition. We conduct extensive and fair comparisons on the unified evaluation benchmark and show that the proposed AGRA framework outperforms previous state-of-the-art methods.

Cystine supplementation rebalances the redox homeostasis of microenvironment in non-small cell lung cancer cells and reverses their resistance to docetaxel.

Continuous docetaxel (DTX) treatment of non-small cell lung cancer induces development of drug resistance, but the mechanism is poorly understood. In this study we performed metabolomics analysis to characterize the metabolic patterns of sensitive and resistant A549 non-small cell lung cancer cells (A549/DTX cells). We showed that the sensitive and resistant A549 cells exhibited distinct metabolic phenotypes: the resistant cells were characterized by an altered microenvironment of redox homeostasis with reduced glutathione and elevated reactive oxygen species (ROS). DTX induction reprogrammed the metabolic phenotype of the sensitive cells, which acquired a phenotype similar to that of the resistant cells: it reduced cystine influx, inhibited glutathione biosynthesis, increased ROS and decreased glutathione/glutathione disulfide (GSH/GSSG); the genes involved in glutathione biosynthesis were dramatically depressed. Addition of the ROS-inducing agent Rosup (25, 50 µg/mL) significantly increased P-glycoprotein expression and reduced intracellular DTX in the sensitive A549 cells, which ultimately acquired a phenotype similar to that of the resistant cells. Supplementation of cystine (1.0 mM) significantly increased GSH synthesis, rebalanced the redox homeostasis of A549/DTX cells, and reversed DTX-induced upregulation of P-glycoprotein, and it markedly improved the effects of DTX and inhibited the growth of A549/DTX in vitro and in vivo. These results suggest that microenvironmental redox homeostasis plays a key role in the acquired resistance of A549 cancer cells to DTX. The enhancement of GSH synthesis by supplementary cystine is a promising strategy to reverse the resistance of tumor cells and has potential for translation in the clinic.

Mechanisms Underlying Gastrodin Alleviating Vincristine-Induced Peripheral Neuropathic Pain.

Gastrodin (GAS) is the main bioactive ingredient of Gastrodia, a famous Chinese herbal medicine widely used as an analgesic, but the underlying analgesic mechanism is still unclear. In this study, we first observed the effects of GAS on the vincristine-induced peripheral neuropathic pain by alleviating the mechanical and thermal hyperalgesia. Further studies showed that GAS could inhibit the current density of NaV1.7 and NaV1.8 channels and accelerate the inactivation process of NaV1.7 and NaV1.8 channel, thereby inhibiting the hyperexcitability of neurons. Additionally, GAS could significantly reduce the over-expression of NaV1.7 and NaV1.8 on DRG neurons from vincristine-treated rats according to the analysis of Western blot and immunofluorescence results. Moreover, based on the molecular docking and molecular dynamic simulation, the binding free energies of the constructed systems were calculated, and the binding sites of GAS on the sodium channels (NaV1.7 and NaV1.8) were preliminarily determined. This study has shown that modulation of NaV1.7 and NaV1.8 sodium channels by GAS contributing to the alleviation of vincristine-induced peripheral neuropathic pain, thus expanding the understanding of complex action of GAS as a neuromodulator.

Characterization of Starch in Cucurbita moschata Germplasms throughout Fruit Development.

Pumpkins (Cucurbita moschata; Cucurbitaceae) are the rich source of nutrients and valued for their biologically active substances to be used for the treatment of several diseases. The contents, composition, and conformation of starch are the significant quality traits of C. moschata. Two germplasms were targeted for analysis regarding the taste difference. Results indicated that the total starch contents and amylose/amylopectin ratio were high in CMO-X as compared to CMO-E during each fruit development stage. Scanning electron microscopy and transmission electron microscopy observations revealed that smooth surface starch granules fused together to enhance the starch accumulation. For a comparison of fruit development in CMO-E and CMO-X, the putative pathway for starch metabolism was developed and homologs were identified for each key gene involved in the pathway. GBSS and SBE were correlated with the difference in the amylose/amylopectin ratio of CMO-E and CMO-X. Conclusively, the developmental regulation of genes associated with starch accumulation can be considered as an important factor for the determination of fruit quality.

[Effects of Renshenjian Decoction on blood and urine metabonomics in type 2 diabetes rats based on ~1H-NMR].

Proton nuclear magnetic resonance(~1H-NMR) is used to investigate the effect of Renshenjian Decoction on serum and urine metabolism of type 2 diabetic rats with insulin resistance induced by high-sugar and high-fat diet combined with low-dose streptozotocin(STZ). After the successful establishment of the insulin resistance model of type 2 diabetes, administration for 35 days, the serum and urine of rats were taken. Once the ~1H-NMR data have been collected and processed, PCA and OPLS-DA were used to analyze them. The results show that: compared with the blank group, the contents of methionine, taurine, α-glucose and ß-glucose in the serum of the model group increased significantly(P<0.001), while the contents of 3-hydroxybutyric acid, lactic acid and unsaturated fatty acids decreased significantly(P<0.01). In the model group, the contents of trimethylamine oxide, glycine, α-glucose, ß-glucose, taurine and phosphocholine in urine increased significantly(P<0.05), while the contents of creatine, lactic acid, acetic acid and citric acid decreased significantly(P<0.05). Compared with the model group, the contents of 3-hydroxybutyric acid and unsaturated fatty acids in serum of rats in the treatment group increased significantly(P<0.05), while the contents of taurine, α-glucose and ß-glucose decreased significantly(P<0.01). In the treatment group, the contents of lactic acid, taurine and creatine in urine increased significantly(P<0.05), while the contents of trimethylamine oxide, glycine, α-glucose, ß-glucose and phosphocholine decreased significantly(P<0.01). The results show that Renshenjian Decoction can regulate metabolic disorder and promote the metabolic phenotype to return to the normal range. It displayed therapeutic effect on type 2 diabetic rats with insulin resistance and provided a certain scientific basis for the biological basic research of Renshenjian Decoction by improving insulin resistance in diabetes mellitus.

Effect of enzymatic degraded polysaccharides from Enteromorpha prolifera on the physical and oxidative stability of fish oil-in-water emulsions.

To explore the potential application of enzymatic degraded polysaccharides from Enteromorpha prolifra (EEP) as antioxidant in fish oils, a stable fish oil emulsion system incorporating EEP was established. Effects of emulsifier (Tween 80, gum arabic and lecithin) and EEP concentration on the physical characteristics of fish oil emulsions were investigated. The results indicated that Tween 80 was the best choice, and 1% (w/w) of EEP was the optimum concentration for the preparation of fish oil emulsions. Influence of EEP on the oxidative stability and physical stability of fish oil emulsions was compared with that of antioxidants VE and TBHQ by determining the physical properties, lipid hydroperoxide formation, secondary reaction products formation, pH and long chain polyunsaturated fatty acid content, during storage at 45 °C. The results indicated that the fish oil emulsion system (5% oil, 1% EEP and 1% Tween 80, w/w) possessed good physical and oxidative stabilities.

The metabolic effect of gut microbiota on drugs.

There are more than 1000 species of microbes reside in the human gut, umbering∼1014 microbes. As the invisible organ of human beings, gut microbiota can usually participate in drug metabolism by producing specific enzymes, such as reductase and hydrolytic enzyme, thus affecting the efficacy, toxicity, and bioavailability of drugs. At least 30 commercially available drugs have been shown to be substrates of gut microbes-derived enzymes, and an increasing number of drugs may have the potential to contact with the distal gut with the help of improved release systems or poor solubility/permeability, more drugs are expected to be found to be metabolized through the gut flora. By collecting examples of intestinal flora participating in the metabolism of synthetic drugs and traditional Chinese medicine components, this article provides a comprehensive reference for future researchers to study drug metabolism by intestinal flora. Noticeably, the composition and quantity of intestinal flora varies among individuals, and can be affected by some drug administration (such as antibiotics) or environmental changes (acute plateau hypoxia). This seems to suggest that intestinal flora could have the potential to be a new drug target to affect the efficacy of drugs which can be metabolized by Intestinal flora. Accordingly, understanding the impact of intestinal flora on drug metabolism and clarifying the drug transformation process is of great significance for guiding rational clinical use, individualized use, toxicological evaluation, and promoting drug discovery and development.

[Advances on network pharmacology in ethnomedicine research].

Ethnomedicine is the precious wealth left by ethnic minorities in their struggle against diseases. It is similar to traditional Chinese medicine in a narrow sense and has the characteristics of multi-component,multi-target and multi-channel synergy. Under the guidance of the theory of ethnomedicine,the combination of ethnomedicine and network pharmacology will help to understand the essence of the prevention and treatment of ethnomedicines in a dynamic and holistic manner. This paper reviews the research progress of network pharmacology applied in ethnomedicine,analyses the problems and challenges existing in the application of network pharmacology in ethnomedicine research at present,such as inaccurate data and information,lack of network analysis platform for effective analysis of dose-effect relationship of chemical constituents and weak basic research of ethnomedicine,and puts forward corresponding prospects.

The neural basis of complex audiovisual objects maintenances in working memory.

Working memory research has primarily concentrated on studying our senses separately; the neural basis of maintaining information from multiple sensory modalities in working memory has been not well elucidated. It is debated whether multisensory information is maintained in the form of modality-specific representations or amodal representations. The present study investigated what brain regions were engaged in both types of complex audiovisual objects maintenances (semantically congruent and incongruent) using functional magnetic resonance imaging and conjunction analysis, and examined in which form to maintain multisensory objects information in working memory. The conjunction analysis showed that there was common brain regions activation involving left parietal cortex (e.g., left angular gyrus, supramarginal gyrus, and precuneus) while maintaining semantically congruent audiovisual object, whereas the common brain regions activation including the bilateral angular, left superior parietal lobule, and left middle temporal gyrus was found during maintaining semantically incongruent audiovisual objects. Importantly, the shared conjoint brain regions activation consists of bilateral angular gyrus and left middle frontal gyrus was observed while maintaining both types of semantically congruent and incongruent complex audiovisual objects. These brain regions may play different role while maintaining these complex multisensory objects, such as supramodel storage per se and intentional attention. The findings of the present studymight support the amodal view that working memory has a central storage system to maintain multisensory information from different sensory inputs.

Isoflavones enhance pharmacokinetic exposure of active lovastatin acid via the upregulation of carboxylesterase in high-fat diet mice after oral administration of Xuezhikang capsules.

Xuezhikang capsule (XZK) is a traditional Chinese medicine that contains lovastatin (Lv) for hyperlipidemia treatment, although it has fewer side effects than Lv. However, the pharmacokinetic mechanisms contributing to its distinct efficacy and low side effects are unclear. Mice were fed a high-fat diet (HFD) for 6 weeks to induce hyperlipidemia. We first conducted the pharmacokinetic studies in HFD mice following oral administration of Lv (10 mg/kg, i.g.) and found that HFD remarkably decreased the active form of Lv (the lovastatin acid, LvA) exposure in the circulation system, especially in the targeting organ liver, with a declined conversion from Lv to LvA, whereas the Lv (responsible for myotoxicity) exposure in muscle markedly increased. Then we compared the pharmacokinetic profiles of Lv in HFD mice after the oral administration of XZK (1200 mg/kg, i.g.) or an equivalent dose of Lv (10 mg/kg, i.g.). A higher exposure of LvA and lower exposure of Lv were observed after XZK administration, suggesting a pharmacokinetic interaction of some ingredients in XZK. Further studies revealed that HFD promoted the inflammation and inhibited carboxylesterase (CES) activities in the intestine and the liver, thus contributing to the lower transformation of Lv into LvA. In contrast, XZK inhibited the inflammation and upregulated CES in the intestine and the liver. Finally, we evaluated the effects of monacolins and phytosterols, the fractional extracts of isoflavones, on inflammatory LS174T or HepG2 cells, which showed that isoflavones inhibited inflammation, upregulated CES, and markedly enhanced the conversion of Lv into LvA. For the first time, we provide evidence that isoflavones and Lv in XZK act in concert to enhance the efficacy and reduce the side effects of Lv.

[Colorectal cancer preventive effect of combined administration of phenolic acids and supercritical extracts from Angelica sinensis].

This study aimed to investigate the colorectal cancer preventive effect of the combined administration of phenolic acids and supercritical extracts from Angelica sinensis. The AOM/DSS model in mice was adopted. Phenolic acids were administrated orally in the initial stage of the model at a dose of 1 g·kg⁻¹ BW, which was combined withtherectal administration with three doses of supercritical extracts (15, 30, 60 g·kg⁻¹ BW). PCNA, 8-oxoguaine, γ-H2AX, iNOS and COX-2 were tested by immunohistochemistry and Western blot assays. The results showed that the combined administration of phenolic acids and supercritical extracts from A. sinensis suppressed the tumor growth and cell proliferation, and DNA damages and inflammatory responses were reduced in a dose-dependent manner. These results indicate that the combined administration of phenolic acids and supercritical extracts from A. sinensis have a certain effect in preventing carcinogenesis.