Loading-effect-based three-dimensional microfabrication empowers on-chip Brillouin optomechanics.

The acousto-optic interaction known as stimulated Brillouin scattering (SBS) has emerged as a fundamental principle for realizing crucial components and functionalities in integrated photonics. However, the main challenge of integrating Brillouin devices is how to effectively confine both optical and acoustic waves. Apart from that, the manufacturing processes for these devices need to be compatible with standard fabrication platforms and streamlined to facilitate their large-scale integration. Here, we demonstrate a novel, to the best of our knowledge, suspended nanowire structure that can tightly confine photons and phonons. Furthermore, tailored for this structure, we introduce a loading-effect-based three-dimensional microfabrication technique, compatible with complementary metal-oxide-semiconductor (CMOS) technology. This innovative technique allows for the fabrication of the entire structure using a single-step lithography exposure, significantly streamlining the fabrication process. Leveraging this structure and fabrication scheme, we have achieved a Brillouin gain coefficient of 1100 W-1m-1 on the silicon-on-insulator platform within a compact footprint. It can support a Brillouin net gain over 4.1 dB with modest pump powers. We believe that this structure can significantly advance the development of SBS on chip, unlocking new opportunities for a large-scale integration of Brillouin-based photonic devices.

Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice / 中西医结合学报

OBJECTIVE@#Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury.@*METHODS@#To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum's protective activity.@*RESULTS@#Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism.@*CONCLUSION@#Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum's protection against liver injury. Please cite this article as: Peng L, Chen HG, Zhou X. Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice. J Integr Med. 2023; 21(3): 289-301.

Alismatis Rhizoma methanolic extract-Effects on metabolic syndrome and mechanisms of triterpenoids using a metabolomic and lipidomic approach.

Alismatis rhizoma is a traditional Chinese medicine. Studies have demonstrated that Alismatis rhizoma also has therapeutic effects on metabolic syndrome. However, the pharmacodynamic material basis and mechanism are still unclear. First, UHPLC/Q-Orbitrap MS was used to detect the chemical components of the Alismatis rhizoma extract, and 31 triterpenoids and 2 sesquiterpenes were preliminarily identified. Then, to investigate the mechanism of the Alismatis rhizoma extract on metabolic syndrome, a mouse model of metabolic syndrome induced by high-fructose drinks was established. The results of serum biochemical analysis showed that the levels of TG, TC, LDL-C, and UA after the Alismatis rhizoma extract treatment were markedly decreased. 1H-NMR was used to conduct non-targeted metabolomics studies. A total of 20 differential metabolites were associated with high-fructose-induced metabolic syndrome, which were mainly correlated with 11 metabolic pathways. Moreover, UHPLC/Q-Orbitrap MS lipidomics analysis found that a total of 53 differential lipids were screened out. The results showed that Alismatis rhizoma extract mainly reduces the synthesis of glycerophospholipid and ceramide and improves the secretion of bile acid. This study shows that the Alismatis rhizoma extract can treat metabolic syndrome mainly by inhibiting energy metabolism, amino acid metabolism, and regulating bile acid to reduce phospholipid content.

Site-specific protein modification by 3-n-butylphthalide in primary hepatocytes: Covalent protein adducts diminished by glutathione and N-acetylcysteine.

AIMS: 3-n-Butylphthalide (NBP) is widely used for the treatment of cerebral ischaemic stroke but can causeliver injury in clinical practice. This study aims to elucidate the underlying mechanisms and propose potential preventive strategies. MAIN METHODS: NBP and its four major metabolites, 3-hydroxy-NBP (3-OH-NBP), 10-hydroxy-NBP, 10-keto-NBP and NBP-11-oic acid, were synthesized and evaluated in primary human or rat hepatocytes (PHHs, PRHs). NBP-related substances or amino acid adducts were identified and semi-quantitated by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS). The target proteins and binding sites were identified by shotgun proteomics based on peptide mass fingerprinting coupled with tandem mass spectrometry and verified by molecular docking. KEY FINDINGS: The toxicity of NBP and its four major metabolites were compared in both PHHs and PRHs, and 3-OH-NBP was found to be the most toxic metabolite. 3-OH-NBP induced remarkable cell death and oxidative stresses in hepatocytes, which correlated well with the levels of glutathione and N-acetylcysteine adducts (3-GSH-NBP and 3-NAC-NBP) in cell supernatants. Additionally, 3-OH-NBP covalently conjugated with intracellular Cys, Lys and Ser, with preferable binding to Cys sites at Myh9 Cys1380, Prdx4 Cys53, Vdac2 Cys48 and Vdac3 Cys36. Furthermore, we found that CYP3A4 induction by rifampicin augmented NBP-induced cell toxicity and supplementing with GSH or NAC alleviated the oxidative stresses and reactive metabolites caused by 3-OH-NBP. SIGNIFICANCE: Our work suggests that glutathione depletion, mitochondrial injury and covalent protein modification are the main causes of NBP-induced hepatotoxicity, which may be prevented by exogenous GSH or NAC supplementation and avoiding concomitant use of CYP3A4 inducers.

Danggui-Shaoyao-San Improves Gut Microbia Dysbiosis and Hepatic Lipid Homeostasis in Fructose-Fed Rats.

Metabolic syndrome (MetS) is a pathological state of many abnormal metabolic sections. These abnormalities are closely related to diabetes, heart pathologies and other vascular diseases. Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine formula that has been used as a therapy for Alzheimer's disease. DSS has rarely been reported in the application of MetS and its mechanism of how it improves gut microbia dysbiosis and hepatic lipid homeostasis. In this study, three extracts of DSS were obtained using water, 50% methanol in water and methanol as extracting solvents. Their chemical substances were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass (UPLC-Q/TOF-MS). Pharmacodynamic effect of the extracts were evaluated by comparison of biochemical factors, 16S rRNA sequencing test for gut microbiota analysis, as well as metabonomic and transcriptomic assessments on liver tissues from fructose-fed rats. This study aimed at investigating DSS's mechanism of regulating blood lipid, anti-inflammation and reducing blood glucose. The results showed that the 50% methanol extract (HME) was more effective. It was worth noting that hydroxysteroid 17ß-dehydrogenase 13 (HSD17ß13) as a critical element of increasing blood lipid biomarker-triglyceride (TG), was decreased markedly by DSS. The influence from upgraded hydroxysteroid 17ß-dehydrogenase 7 (HSD17ß7) may be stronger than that from downgraded Lactobacillus in the aspect of regulating back blood lipid biomarker-total cholesterol (TC). The differential down-regulation of tumornecrosis factor alpha (TNF-α) and the significant up-regulation of Akkermansia showed the effective effect of anti-inflammation by DSS. The declining glycine and alanine induced the lowering glucose and lactate. It demonstrated that DSS slowed down the reaction of gluconeogenesis to reduce the blood glucose. The results demonstrated that DSS improved pathological symptoms of MetS and some special biochemical factors in three aspects by better regulating intestinal floras and improving hepatic gene expressions and metabolites.

The essential elements of Alzheimer's disease.

Treatments for Alzheimer's disease (AD) directed against the prominent amyloid plaque neuropathology are yet to be proved effective despite many phase 3 clinical trials. There are several other neurochemical abnormalities that occur in the AD brain that warrant renewed emphasis as potential therapeutic targets for this disease. Among those are the elementomic signatures of iron, copper, zinc, and selenium. Here, we review these essential elements of AD for their broad potential to contribute to Alzheimer's pathophysiology, and we also highlight more recent attempts to translate these findings into therapeutics. A reinspection of large bodies of discovery in the AD field, such as this, may inspire new thinking about pathogenesis and therapeutic targets.

Piceatannol inhibits pyroptosis and suppresses oxLDL-induced lipid storage in macrophages by regulating miR-200a/Nrf2/GSDMD axis.

As a major bioactive compound from grapes, piceatannol (PIC) has been reported to exert anti-atherosclerotic activity in various studies. Nevertheless, the mechanism underlying the effect of piceatannol against atherosclerosis (AS) is elusive. Our study identified miR-200a/Nrf2/GSDMD signaling pathway as critical mediators in the effect of piceatannol on macrophages. In the present study, we confirmed that treatment of piceatannol repressed the oxLDL-induced lipid storage in macrophages. Compared with control group, piceatannol inhibited TG storage and the activity of caspase1. It is noting that in response to oxLDL challenge, piceatannol abated the pyroptosis in RAW264.7 cells, with a decreased expression of caspase1, gasdermin D (GSDMD), IL-18, IL-1ß and NLRP3. Moreover, we investigated the role of microRNA (miR)-200a/Nrf2 signaling pathway in the effect of piceatannol. The results declared that after transfection of si-miR-200a or si-Nrf2 plasmids, the effects of piceatannol on macrophages were converted, including lipid storage and pyroptosis. Importantly, si-miR-200a plasmid reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), indicating that miR-200a acted as an enhancer of Nrf2 in macrophages. Collectively, our findings demonstrate that piceatannol exerts anti-atherosclerotic activity on RAW264.7 cells by regulating miR-200a/Nrf2/GSDMD signaling. The present study is the first time to identify miR-200a as a candidate target in AS and declared an association between miR-200a and pyroptosis, which provides a novel therapy for the treatment of AS.

Iron promotes the clearance of α-synuclein: An Editorial for 'H63D variant of the homeostatic iron regulator (HFE) gene alters α-synuclein expression, aggregation, and toxicity" on page 177.

Both elevated iron and α-synuclein (α-syn) aggregates are neuropathological hallmarks of Parkinson's disease (PD). It has been previously shown that iron promotes α-synuclein aggregation, and α-synuclein dysfunction impairs iron metabolism. In their latest work, Kim et al. have shown that the H63D variant of the homeostatic iron regulator (HFE) facilitates α-syn degradation via REDD1-mediated autophagy. Mice with the H63D variant of HFE were protected against α-syn toxicity. These results may shed light on recent clinical studies of PD using iron chelation therapy.

Fibrillar α-synuclein toxicity depends on functional lysosomes.

Neurodegeneration in Parkinson's disease (PD) can be recapitulated in animals by administration of α-synuclein preformed fibrils (PFFs) into the brain. However, the mechanism by which these PFFs induce toxicity is unknown. Iron is implicated in PD pathophysiology, so we investigated whether α-synuclein PFFs induce ferroptosis, an iron-dependent cell death pathway. A range of ferroptosis inhibitors were added to a striatal neuron-derived cell line (STHdhQ7/7 cells), a dopaminergic neuron-derived cell line (SN4741 cells), and WT primary cortical neurons, all of which had been intoxicated with α-synuclein PFFs. Viability was not recovered by these inhibitors except for liproxstatin-1, a best-in-class ferroptosis inhibitor, when used at high doses. High-dose liproxstatin-1 visibly enlarged the area of a cell that contained acidic vesicles and elevated the expression of several proteins associated with the autophagy-lysosomal pathway similarly to the known lysosomal inhibitors, chloroquine and bafilomycin A1. Consistent with high-dose liproxstatin-1 protecting via a lysosomal mechanism, we further de-monstrated that loss of viability induced by α-synuclein PFFs was attenuated by chloroquine and bafilomycin A1 as well as the lysosomal cysteine protease inhibitors, leupeptin, E-64D, and Ca-074-Me, but not other autophagy or lysosomal enzyme inhibitors. We confirmed using immunofluorescence microscopy that heparin prevented uptake of α-synuclein PFFs into cells but that chloroquine did not stop α-synuclein uptake into lysosomes despite impairing lysosomal function and inhibiting α-synuclein toxicity. Together, these data suggested that α-synuclein PFFs are toxic in functional lysosomes in vitro. Therapeutic strategies that prevent α-synuclein fibril uptake into lysosomes may be of benefit in PD.

Mixed Reality Combined with Three-Dimensional Printing Technology in Total Hip Arthroplasty: An Updated Review with a Preliminary Case Presentation.

Three-dimensional (3D) printing technology, virtual reality, and augmented reality technology have been used to help surgeons to complete complex total hip arthroplasty, while their respective shortcomings limit their further application. With the development of technology, mixed reality (MR) technology has been applied to improve the success rate of complicated hip arthroplasty because of its unique advantages. We presented a case of a 59-year-old man with an intertrochanteric fracture in the left femur, who had received a prior left hip fusion. After admission to our hospital, a left total hip arthroplasty was performed on the patient using a combination of MR technology and 3D printing technology. Before surgery, 3D reconstruction of a certain bony landmark exposed in the surgical area was first performed. Then a veneer part was designed according to the bony landmark and connected to a reference registration landmark outside the body through a connecting rod. After that, the series of parts were made into a holistic reference registration instrument using 3D printing technology, and the patient's data for bone and surrounding tissue, along with digital 3D information of the reference registration instrument, were imported into the head-mounted display (HMD). During the operation, the disinfected reference registration instrument was installed on the selected bony landmark, and then the automatic real-time registration was realized by HMD through recognizing the registration landmark on the reference registration instrument, whereby the patient's virtual bone and other anatomical structures were quickly and accurately superimposed on the real body of the patient. To the best of our knowledge, this is the first report to use MR combined with 3D printing technology in total hip arthroplasty.

Dual sensing reporter system of assembled gold nanoparticles toward the sequential colorimetric detection of adenosine and Cr(III).

A facile and sensitive sequential colorimetric detection strategy for adenosine and Cr3+ has been presented by using the aptamer and 11-mercaptoundecanoic acid assembled gold nanoparticles. The thiolated DNA and 11-mercaptoundecanoic acid was simultaneously assembled to the surface of gold nanoparticles in one step by gold-sulfur interaction. Adenosine aptamer was linked to functionalized gold nanaoparticles based on the strict complementary nature of the DNA base pairs. Conformational change of aptamer will be induced due to its specific binding with targets. As a result, this aptamer tethered aggregated nanoparticles underwent fast disassembly into dispersed nanoparticles upon binding of adenosine, and this distance change between particles induced a distinct solution color changing from blue to red. The dispersed particles were sensitive to Cr3+ due to the chelation effect between the carboxyl group of 11-mercaptoundecanoic acid and metal ions, and further occurred obvious aggregation accompanying with a color change from red to blue. Depended on this principle, a sensitive and selective sequential colorimetric sensor for detection of adenosine and Cr3+ was developed. The proposed colorimetric sensor exhibited wide linear ranges and low detection limits towards the detection of adenosine and Cr3+. Regarding adenosine, linear range was 1 × 10-7 ∼ 1 × 10-4 M with low detection limit of 1.8 × 10-8 M, and the naked eye detection limit was estimated as 20 µM. With regard to Cr3+, good linear relationship was ranged from 1 × 10-10 to 1 × 10-6 M with low detection limit of 1.7 × 10-11 M，and the naked eye detection limit was as low as 0.1 nM. Meanwhile, bifunctional recognition was successfully used for practical human urine samples with good recoveries from 89.0% to 112.6% for adenosine and 90.2%-113.4% for Cr3+. It also highlights the potential applications of other aptamers and ligands in cascade analysis of other analytes.

Predicting combinative drug pairs via multiple classifier system with positive samples only.

BACKGROUND AND OBJECTIVE: Due to the synergistic effects of drugs, drug combination is one of the effective approaches for treating complex diseases. However, the identification of drug combinations by dose-response methods is still costly. It is promising to develop supervised learning-based approaches to predict potential drug combinations on a large scale. Nevertheless, these approaches have the inadequate utilization of heterogeneous features, which causes the loss of information useful to classification. Moreover, they have an intrinsic bias, because they assume unknown drug pairs as non-combinations, of which some could be real drug combinations in practice. METHODS: To address above issues, this work first designs a two-layer multiple classifier system (TLMCS) to effectively integrate heterogeneous features involving anatomical therapeutic chemical codes of drugs, drug-drug interactions, drug-target interactions, gene ontology of drug targets, and side effects. To avoid the bias caused by labelling unknown samples as negative, it then utilizes the one-class support vector machines, (which requires no negative instance and only labels approved drug combinations as positive instances), as the member classifiers in TLMCS. Last, both a 10-fold cross validation (10-CV) and a novel prediction are performed to validate the performance of TLMCS. RESULTS: The comparison with three state-of-the-art approaches under 10-CV exhibits the superiority of TLMCS, which achieves the area under the receiver operating characteristic curve = 0.824 and the area under the precision-recall curve = 0.372. Moreover, the experiment under the novel prediction demonstrates its ability, where 9 out of the top-20 predicted combinative drug pairs are validated by checking the published literature. Furthermore, for each of the newly-validated drug combinations, this work analyses the combining mode of the member drugs and investigates their relationship in terms of drug targeting pathways. CONCLUSIONS: The proposed TLMCS provides an effective framework to integrate those heterogeneous features and is trained by only positive samples such that the bias of taking unknown drug pairs as negative samples can be avoided. Furthermore, its results in the novel prediction reveal five types of drug combinations and three types of drug relationships in terms of pathways.

[Effects of centellaasiatica granule on the expression of Smad 2/3, Smad 7 and collagen â £ in the mesangial cells stably expressed TGF-ß1].

OBJECTIVES: Stably expressed transforming growth factor -beta 1(TGF-ß1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed. METHODS: Lipofectin method was used to transfect TGF-ß1 vector into MC, and the stably expressed TGF-ß1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-ß1 group:stably expressed TGF-ß1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-ß1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-ß1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-ß1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The contents of TGF-ß1 and collagen Ⅳ in the culture medium of stably-expressed TGF-ß1 MC were increased significantly, and the CA could reverse the effects of TGF-ß1. The expressions of mRNA and protein of TGF-ß1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-ß1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-ß1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-ß1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression. CONCLUSIONS: The MCs stably-expressed TGF-ß1 can activate the TGF-ß1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-ß1/Smad signal pathway.

Broccoli Sprout Extract Alleviates Alcohol-Induced Oxidative Stress and Endoplasmic Reticulum Stress in C57BL/6 Mice.

The potential efficacy of sulforaphane in protecting alcohol-induced hepatic injury in vivo and its underlying mechanism were investigated. Male C57BL/6 mice were orally administrated with broccoli sprout extract (BSE) containing sulforaphane [7.6, 25.2, and 50.4 mg/kg of body weight (bw)] once a day for 14 days. At the 13th day, mice were challenged with alcohol (5 g/kg of bw) every 12 h for 3 times, which increased malondialdehyde (MDA) levels (4.44 ± 1.24 nmol/mg of protein, p < 0.01) in the liver. Our results showed that low-, medium-, and high-dose BSE markedly reversed the decrease of antioxidant capacity through enhancing glutathione (GSH) (2.07 ± 0.31 mg/g of protein, p < 0.05; 2.31 ± 0.32 mg/g of protein, p < 0.01; and 2.46 ± 0.21 mg/g of protein, p < 0.01), superoxide dismutase (SOD) (483.20 ± 62.76 units/mg of protein; 500.81 ± 49.82 units/mg of protein, p < 0.05; and 605.00 ± < 64.32 units/mg of protein, p < 0.01), glutathione peroxidase (GSH-Px) (318 ± 60.74 units/mg of protein; 400.67 ± 72.47 units/mg of protein, p < 0.01; and 394.72 ± 62.97 units/mg of protein, p < 0.01), and glutathione S-transferase (GST) (31.84 ± 6.34 units/mg of protein, p < 0.05; 30.34 ± 6.40 units/mg of protein, p < 0.05; and 38.08 ± 7.05 units/mg of protein, p < 0.01) in the liver. The protective actions are also associated activation of phase 2 enzymes via nuclear erythoriod-2-related factor 2 (Nrf2). The endoplasmic reticulum (ER)-stress-specific proteins, such as glucose-regulated protein 78 (GRP78), activating transcription factor 6, and protein kinase RNA (PKR)-like ER kinase (PERK), were also significantly attenuated by BSE. These results indicate that BSE protects the liver against alcohol challenge via upregulating antioxidant capacity and downregulating ER stress.

Effects of centellaasiatica granule on the expression of Smad 2/3, Smad 7 and collagen Ⅳ in the mesangial cells stably expressed TGF-β1 / 中国应用生理学杂志

OBJECTIVES@#Stably expressed transforming growth factor -beta 1(TGF-β1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed.@*METHODS@#Lipofectin method was used to transfect TGF-β1 vector into MC, and the stably expressed TGF-β1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-β1 group:stably expressed TGF-β1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-β1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-β1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-β1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot.@*RESULTS@#The contents of TGF-β1 and collagen Ⅳ in the culture medium of stably-expressed TGF-β1 MC were increased significantly, and the CA could reverse the effects of TGF-β1. The expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-β1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-β1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression.@*CONCLUSIONS@#The MCs stably-expressed TGF-β1 can activate the TGF-β1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-β1/Smad signal pathway.

Predicting combinative drug pairs towards realistic screening via integrating heterogeneous features.

BACKGROUND: Drug Combination is one of the effective approaches for treating complex diseases. However, determining combinative drug pairs in clinical trials is still costly. Thus, computational approaches are used to identify potential drug pairs in advance. Existing computational approaches have the following shortcomings: (i) the lack of an effective integration of heterogeneous features leads to a time-consuming training and even results in an over-fitted classifier; and (ii) the narrow consideration of predicting potential drug combinations only among known drugs having known combinations cannot meet the demand of realistic screenings, which pay more attention to potential combinative pairs among newly-coming drugs that have no approved combination with other drugs at all. RESULTS: In this paper, to tackle the above two problems, we propose a novel drug-driven approach for predicting potential combinative pairs on a large scale. We define four new features based on heterogeneous data and design an efficient fusion scheme to integrate these feature. Moreover importantly, we elaborate appropriate cross-validations towards realistic screening scenarios of drug combinations involving both known drugs and new drugs. In addition, we perform an extra investigation to show how each kind of heterogeneous features is related to combinative drug pairs. The investigation inspires the design of our approach. Experiments on real data demonstrate the effectiveness of our fusion scheme for integrating heterogeneous features and its predicting power in three scenarios of realistic screening. In terms of both AUC and AUPR, the prediction among known drugs achieves 0.954 and 0.821, that between known drugs and new drugs achieves 0.909 and 0.635, and that among new drugs achieves 0.809 and 0.592 respectively. CONCLUSIONS: Our approach provides not only an effective tool to integrate heterogeneous features but also the first tool to predict potential combinative pairs among new drugs.

Establishment of Quality Standard System for Gui Erbai Gel Based on a Method of A System to Multiple Evaluation / 中国药师

Objective:To establish the quality standard system of Gui Erbai gel based on a method ofa system to multiple evalu-ation and discuss the feasibility of the method used for the quality standard for traditional Chinese medicine. Methods:TLC identifi-cation of Gui Erbai gel was established by one thin layer system. An HPLC method was used to detect 6 active components in Gui Erbai gel. Results:Five active components in the gel could be identified by one thin layers system simultaneously with clear spots and good separation. Six active components in the gel could be determined by the same HPLC system with high accuracy. The average content of podophylotoxin,quercetin,kaempferol,imperatorin,dictamnine and rutin is as follows 0. 154,0. 052,0. 138,0. 051,0. 060,0. 048 mg· g-1 . RSD<3％. Conclusion:The established method based on a system to multiple evaluation can be used for the quality standard establishment for Gui Erbai gel with the properties of promising feasibility, simple operation, low cost, high accuracy and good stabili-ty.

Antiepileptic activity of total triterpenes isolated from Poria cocos is mediated by suppression of aspartic and glutamic acids in the brain.

CONTEXT: Triterpenes from Poria cocos Wolf (Polyporaceae) have been used to treat various diseases in traditional Chinese medicine. However, the antiepileptic effects and mechanism are not fully understood. OBJECTIVE: The objective of this study is to investigate the antiepileptic properties of total triterpenes (TTP) from the whole P. cocos. MATERIALS AND METHODS: The ethanol extract TTP was identified by HPLC fingerprint analysis. Male ICR mice were gavaged (i.g.) with TTP (5, 20, 80 or 160 mg/kg) or reference drugs twice a day for 7 d. Antiepileptic activities of TTP were evaluated by maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizures in mice for 30 and 60 min, respectively. Locomotor activity and Rota-rod tests were performed for 60 min and 5 min, respectively. The levels of glutamic acid (Glu), aspartic acid (Asp), γ-aminobutyric acid (GABA) and glycine (Gly) in convulsive mice were estimated. The chronic epileptic model of Wistar rats was built to measure expressions of glutamate decarboxylase 65 (GAD65) and GABAA in rat brain after TTP treatment. RESULTS: The LC50 of TTP (i.g.) was above 6 g/kg. TTP (5-160 mg/kg) protected mice against MES- and PTZ-induced convulsions at 65.0% and 62.5%, respectively, but have no effect on rota-rod treadmill; TTP (20-160 mg/kg) significantly reduced the locomotor activities, shortened the onset of pentobarbital sodium-induced sleep; TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABAA expressions in chronic epileptic rats at doses usage. DISCUSSION AND CONCLUSION: TTP extracted from P. cocos possessed potential antiepileptic properties and is a candidate for further antiepileptic drug development.

Design, synthesis and fungicidal activity of N-substituted benzoyl-1,2,3,4-tetrahydroquinolyl-1-carboxamide.

To find a new lead compound with high biological activity, a series of N-substituted benzoyl-1,2,3,4-tetrahydroquinolyl-1-carboxamide were designed using linking active substructures method. The target compounds were synthesized from substituted benzoic acid by four steps and their structures were confirmed by (1)H NMR, IR spectrum and elemental analysis. The in vitro bioassay results indicated that some target compounds exhibited excellent fungicidal activities, and the position of the substituents played an important role in fungicidal activities. Especially, compound 5n, exhibited better fungicidal activities than the commercial fungicide flutolanil against two tested fungi Valsa mali and Sclerotinia sclerotiorum, with EC50 values of 3.44 and 2.63mg/L, respectively. And it also displayed good in vivo fungicidal activity against S. sclerotiorum with the EC50 value of 29.52mg/L.

[Optimization of Extraction Technology of Yiyi Fuzi Baijiang Powder by Orthogonal Design].

Objective: To optimize the optimum extraction technology of Yiyi Fuzi Baijiang powder. Methods: Orthogonal design was used,the extraction rate of Coicis Semen oil was used to determine the ethanol extraction technology of Coicis Semen,the extraction rate of protocatechuic acid,chlorogenic acid and benzoylmesaconine were used to determine the water extraction technology of Aconiti Lateralis Radix Praeparata and Herba Patriniae. Results: The optimum extraction technology of Coicis Semen was obtained,alcohol was consumed as four times of the herb amount,and ultrasonic extracted three times with 20 minutes each time; the optimum extraction technology of Aconiti Lateralis Radix Praeparata and Herba Patriniae was obtained,water was consumed as ten times of the herb amount,and extracted for 1. 0 h for Aconiti Lateralis Radix Praeparata and then Herba Patriniae was added and extracted for 45 minutes for the first time; in the second time,water was consumed as 8 times of the herb amount,and extracted for 30 minutes for dregs of herbs. Conclusion: The optimum extraction technology is stable and feasible,in which can give a reference to the preparation research of Yiyi Fuzi Baijiang powder.