Desloratadine alleviates ALS-like pathology in hSOD1G93A mice via targeting 5HTR2A on activated spinal astrocytes.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive loss of motor neurons in the spinal cord, cerebral cortex and brain stem. ALS is characterized by gradual muscle atrophy and dyskinesia. The limited knowledge on the pathology of ALS has impeded the development of therapeutics for the disease. Previous studies have shown that autophagy and astrocyte-mediated neuroinflammation are involved in the pathogenesis of ALS, while 5HTR2A participates in the early stage of astrocyte activation, and 5HTR2A antagonism may suppress astrocyte activation. In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR2A antagonist, in human SOD1G93A (hSOD1G93A) ALS model mice, and elucidated the underlying mechanisms. HSOD1G93A mice were administered DLT (20 mg·kg-1·d-1, i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR2A) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. We showed that DLT administration significantly delayed ALS symptom onset time, prolonged lifespan and ameliorated movement disorders, gastrocnemius injury and spinal motor neuronal loss in hSOD1G93A mice. Spinal cord-specific knockdown of 5HTR2A by intrathecal injection of adeno-associated virus9 (AAV9)-si-5Htr2a also ameliorated ALS pathology in hSOD1G93A mice, and occluded the therapeutic effects of DLT administration. Furthermore, we demonstrated that DLT administration promoted autophagy to reduce mutant hSOD1 levels through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocyte neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice. In summary, 5HTR2A antagonism shows promise as a therapeutic strategy for ALS, highlighting the potential of DLT in the treatment of the disease. DLT as a 5HTR2A antagonist effectively promoted autophagy to reduce mutant hSOD1 level through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocytic neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice.

Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice.

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H1 receptor antagonist, but also acted as a selective antagonist of 5HTR2A. In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR2A/c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR2A. We conclude that spinal 5HTR2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR2A-specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR2A/c-FOS pathway. Our findings have supported that spinal 5HTR2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy.

Vincamine as an agonist of G-protein-coupled receptor 40 effectively ameliorates diabetic peripheral neuropathy in mice.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, which has yet no curable medication. Neuroinflammation and mitochondrial dysfunction are tightly linked to DPN pathology. G-protein-coupled receptor 40 (GPR40) is predominantly expressed in pancreatic ß-cells, but also in spinal dorsal horn and dorsal root ganglion (DRG) neurons, regulating neuropathic pain. We previously have reported that vincamine (Vin), a monoterpenoid indole alkaloid extracted from Madagascar periwinkle, is a GPR40 agonist. In this study, we evaluated the therapeutic potential of Vin in ameliorating the DPN-like pathology in diabetic mice. Both STZ-induced type 1 (T1DM) and db/db type 2 diabetic (T2DM) mice were used to establish late-stage DPN model (DPN mice), which were administered Vin (30 mg·kg-1·d-1, i.p.) for 4 weeks. We showed that Vin administration did not lower blood glucose levels, but significantly ameliorated neurological dysfunctions in DPN mice. Vin administration improved the blood flow velocities and blood perfusion areas of foot pads and sciatic nerve tissues in DPN mice. We demonstrated that Vin administration protected against sciatic nerve myelin sheath injury and ameliorated foot skin intraepidermal nerve fiber (IENF) density impairment in DPN mice. Moreover, Vin suppressed NLRP3 inflammasome activation through either ß-Arrestin2 or ß-Arrestin2/IκBα/NF-κB signaling, improved mitochondrial dysfunction through CaMKKß/AMPK/SIRT1/PGC-1α signaling and alleviated oxidative stress through Nrf2 signaling in the sciatic nerve tissues of DPN mice and LPS/ATP-treated RSC96 cells. All the above-mentioned beneficial effects of Vin were abolished by GPR40-specific knockdown in dorsal root ganglia and sciatic nerve tissues. Together, these results support that pharmacological activation of GPR40 as a promising therapeutic strategy for DPN and highlight the potential of Vin in the treatment of this disease.

Patchouli alcohol as a selective estrogen receptor ß agonist ameliorates AD-like pathology of APP/PS1 model mice.

Clinical evidence shows that postmenpausal women are almost twice as likely to develop Alzheimer's disease (AD) as men of the same age, and estrogen is closely related to the occurrence of AD. Estrogen receptor (ER) α is mainly expressed in the mammary gland and other reproductive organs like uterus while ERß is largely distributed in the hippocampus and cardiovascular system, suggesting that ERß selective agonist is a valuable drug against neurodegenerative diseases with low tendency in inducing cancers of breast and other reproductive organs. In this study we identified a natural product patchouli alcohol (PTA) as a selective ERß agonist which improved the cognitive defects in female APP/PS1 mice, and explore the underlying mechanisms. Six-month-old female APP/PS1 mice were administered PTA (20, 40 mg · kg-1 · d-1, i.g.) for 90 days. We first demonstrated that PTA bound to ERß with a dissociation constant (KD) of 288.9 ± 35.14 nM in microscale thermophoresis. Then we showed that PTA administration dose-dependently ameliorated cognitive defects evaluated in Morris water maze and Y-maze testes. Furthermore, PTA administration reduced amyloid plaque deposition in the hippocampus by promoting microglial phagocytosis; PTA administration improved synaptic integrity through enhancing BDNF/TrkB/CREB signaling, ameliorated oxidative stress by Catalase level, and regulated Bcl-2 family proteins in the hippocampus. The therapeutic effects of PTA were also observed in vitro: PTA (5, 10, 20 µM) dose-dependently increased phagocytosis of o-FAM-Aß42 in primary microglia and BV2 cells through enhancing ERß/TLR4 signaling; PTA treatment ameliorated o-Aß25-35-induced reduction of synapse-related proteins VAMP2 and PSD95 in primary neurons through enhancing ERß/BDNF/TrkB/CREB pathways; PTA treatment alleviated o-Aß25-35-induced oxidative stress in primary neurons through targeting ERß and increasing Catalase expression. Together, this study has addressed the efficacy of selective ERß agonist in the amelioration of AD and highlighted the potential of PTA as a drug lead compound against the disease.

Asymmetric Catalytic Approach to Multilayer 3D Chirality.

Invited for the cover of this issue is Guigen Li and co-workers at Texas Tech University and Nanjing University. The cover artwork shows that chirality phenomena exists in the universe and in nature, including at micro and molecular levels. Read the full text of the article at 10.1002/chem.202100700.

Asymmetric Catalytic Approach to Multilayer 3D Chirality.

The first asymmetric catalytic approach to multilayer 3D chirality has been achieved by using Suzuki-Miyaura cross-couplings. New chiral catalysts were designed and screened under various catalytic systems that proved chiral amide-phosphines to be more efficient ligands than other candidates. The multilayer 3D framework was unambiguously determined by X-ray structural analysis showing a parallel pattern of three layers consisting of top, middle and bottom aromatic rings. The X-ray structure of a catalyst complex, dichloride complex of Pd-phosphine amide, was obtained revealing an interesting asymmetric environment nearby the Pd metal center. Three rings of multilayer 3D products can be readily changed by varying aromatic ring-anchored starting materials. The resulting multilayer products displayed strong luminescence under UV irradiation and strong aggregation-induced emission (AIE). In the future, this work would benefit not only the field of asymmetric synthesis but also materials science, in particular polarized organic electronics, optoelectronics and photovoltaics.

MPT64 assays for the rapid detection of Mycobacterium tuberculosis.

BACKGROUND: Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (MTB). An estimated 1.7 billion people worldwide are infected with Mycobacterium tuberculosis (LTBI) during the incubation period without any obvious symptoms. Because of MTB's high infection and mortality rates, there is an urgent need to develop a fast, portable, and sensitive diagnostic technology for its detection. METHODS: We included research from PubMed, Cochrane Library, Web of Science, and Embase and extracted the data. MetaDisc and STATA were used to build forest plots, Deek's funnel plot, Fagan plot, and bivariate boxplot for analysis. RESULTS: Forty-six articles were analyzed, the results of which are as follows: sensitivity and specificity were 0.92 (0.91-0.93) and 0.95 (0.94-0.95) respectively. The NLR and PLR were 0.04 (95% CI 0.03-0.07) and 25.32 (95% CI 12.38-51.78) respectively. DOR was 639.60 (243.04-1683.18). The area under the SROC curve (AUC) was 0.99. CONCLUSIONS: MPT64 exhibits good diagnostic efficiency for MTB. There is no obvious heterogeneity between the three commercial kits.

High-throughput diagnosis of human pathogens and fecal contamination in marine recreational water.

Waterborne pathogens and their associated diseases are major threats to public health, and surveillance of pathogens and identification of the sources of pollution are imperative for preventing infections. However, simultaneously quantitative detection of multiple pathogens and pollution sources in water environments is the major challenge. In this study, we developed and validated a highly sensitive (mostly >80%) and highly specific (>99%) high-throughput quantitative PCR (HT-qPCR) approach, which could simultaneously quantify 68 marker genes of 33 human pathogens and 23 fecal markers of 10 hosts. The HT-qPCR approach was then successfully used to investigate pathogens and fecal pollution in marine recreational water samples of Xiamen, China. Totally, seven pathogenic marker genes were found in 13 beach bathing waters, which targeted Acanthamoeba spp., Clostridium perfringens, enteropathogenic Escherichia coli, Klebsiella pneumoniae, Vibrio cholera/V. parahaemolyticus and Legionella spp.. Fecal markers from human and dog were the most frequently detected, indicating human and dog feces were the main contamination in the recreational waters. Nanopore sequencing of full-length 16S rRNA gene revealed that 28 potential human pathogens were detected and electrical conductivity, salinity, oxidation-reduction potential and dissolved oxygen were significantly correlated with the variation in bacterial community. Our results demonstrated that HT-qPCR approach had the potential rapid quantification of microbial contamination, providing useful data for assessment of microbial pathogen associated health risk and development of management practices to protect human health.

Unraveling the Mechanisms of the Excited-State Intermolecular Proton Transfer (ESPT) for a D-π-A Molecular Architecture.

Precise revealing the mechanisms of excited-state intermolecular proton transfer (ESPT) and the corresponding geometrical relaxation upon photoexcitation and photoionization remains a formidable challenge. In this work, the compound (E)-4-(((4H-1,2,4-triazol-4-yl)imino)methyl)-2,6-dimethoxyphenol (TIMDP) adopting a D-π-A molecular architecture featuring a significant intramolecular charge transfer (ICT) effect has been designed. With the presence of perchloric acid (35 %), TIMDP can be dissolved through the formation of a HClO4 -H2 O-OH(TIMDP)-N(TIMDP) hydrogen-bonding bridge. At the ground state, the ICT effect is dominant, giving birth to crystals of TIMDP. Upon external stimuli (e.g., UV light irradiation, electro field), the excited state is achieved, which weakens the ICT effect, and significantly promotes the ESPT effect along the hydrogen-bonding bridge, resulting in crystals of [HTIMDP]+ ⋅[H2 O]⋅[ClO4 ]- . As a consequence, the mechanisms of the ESPT can be investigated, which distorted the D-π-A molecular architecture, tuned the emission color with the largest Stokes shift of 242 nm, and finally, high photoluminescence quantum yields (12 %) and long fluorescence lifetimes (8.6 µs) have achieved. These results not only provide new insight into ESPT mechanisms, but also open a new avenue for the design of efficient ESPT emitters.

Porous High-Valence Metal-Organic Framework Featuring Open Coordination Sites for Effective Water Adsorption.

The design and preparation of a porous high-valence metal-organic framework (MOF) featuring open coordination sites are of utmost importance for the development of adsorbent materials. Here in this work, the three-dimensional (3D) high-valence MOF [Er(dcbp)3/2(DMF)(H2O)2]·2H2O (HV-MOF-1; H2dcbp = 4,4'-dicarboxy-2,2'-bipyridine, DMF = N,N-dimethylformamide), which possesses permanent porosity and two open coordination sites, has been prepared and characterized. In the 3D framework, the dcbp molecules display two different bridging styles, resulting in ordered diamondlike pores with bared carboxyl oxygen and pyridine nitrogen atoms on dcbp exposed directly to the pores, generating hydrophilic characteristics and high water affinity. In addition, the open coordination sites act as arms to fix the adsorbed water molecules, providing high water adsorption capacity (5.95 mmol g-1) and selectivity. More importantly, the activated HV-MOF-1 species shows an energy-saving step for recycling (operation under 120 °C), demonstrating promise as a candidate for an adsorbent material with considerable water adsorption-desorption cycles.

The role of MAPK signaling pathway in formation of EMT in oral squamous carcinoma cells induced by TNF-α.

To study the role of MAPK signaling pathway in the development of Epithelial-mesenchymal transition in oral squamous cell carcinoma induced by inflammatory factor TNF-α. After the action of TNF-α, the expression of JNK, ERK, P38 in MAPK signaling pathway increased and the expression of E-cadherin, Claudin1 decreased significantly compared to the normal control group. After the addition of corresponding inhibitor, the expression of JNK, ERK, P38 decreased and the expression of E-cadherin, Claudin1 increased compared with TNF-α group. TNF-α regulated the role of EMT in promoting the invasion and metastasis of oral squamous carcinoma cells through MAPK signaling pathway.

Nitazoxanide, an anti-parasitic drug, efficiently ameliorates learning and memory impairments in AD model mice.

The pathogenesis of Alzheimer's disease (AD) is characterized by both accumulation of ß-amyloid (Aß) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular Aß clearance. Thus targeting autophagy becomes a promising strategy for discovery of drug leads against AD. In the present study, we established a platform to discover autophagy stimulator and screened the lab in-house FDA-approved drug library. We found that anti-parasitic drug nitazoxanide (NTZ) was an autophagy activator and could efficiently improve learning and memory impairments in APP/PS1 transgenic mice. In BV2 cells and primary cortical astrocytes, NTZ stimulated autophagy and promoted Aß clearance by inhibiting both PI3K/AKT/mTOR/ULK1 and NQO1/mTOR/ULK1 signaling pathways; NTZ treatment attenuated LPS-induced inflammation by inhibiting PI3K/AKT/IκB/NFκB signaling. In SH-SY5Y cells and primary cortical neurons, NTZ treatment restrained tau hyperphosphorylation through inhibition of PI3K/AKT/GSK3ß pathway. The beneficial effects and related signaling mechanisms from the in vitro studies were also observed in APP/PS1 transgenic mice following administration of NTZ (90 mg·kg-1·d-1, ig) for 100 days. Furthermore, NTZ administration decreased Aß level and senile plaque formation in the hippocampus and cerebral cortex of APP/PS1 transgenic mice, and improved learning and memory impairments in Morris water maze assay. In conclusion, our results highlight the potential of NTZ in the treatment of AD.

A Wind Estimation Method with an Unmanned Rotorcraft for Environmental Monitoring Tasks.

Wind velocity (strength and direction) is an important parameter for unmanned aerial vehicle (UAV)-based environmental monitoring tasks. A novel wind velocity estimation method is proposed for rotorcrafts. Based on an extended state observer, this method derives the wind disturbance from rotors' speeds and rotorcraft's acceleration and position. Then the wind disturbance is scaled to calculate the airspeed vector, which is substituted into a wind triangle to obtain the wind velocity. Easy-to-implement methods for calculating the rotorcraft's thrust and drag coefficient are also proposed, which are important parameters to obtain the wind drag and the airspeed, respectively. Simulations and experiments using a quadrotor in both hovering and flight conditions have validated the proposed method.

Characteristics of N-Acylhomoserine Lactones Produced by Hafnia alvei H4 Isolated from Spoiled Instant Sea Cucumber.

This study aimed to identify N-acylhomoserine lactone (AHL) produced by Hafnia alvei H4, which was isolated from spoiled instant sea cucumber, and to investigate the effect of AHLs on biofilm formation. Two biosensor strains, Chromobacterium violaceum CV026 and Agrobacterium tumefaciens KYC55, were used to detect the quorum sensing (QS) activity of H. alvei H4 and to confirm the existence of AHL-mediated QS system. Thin layer chromatography (TLC) and high resolution triple quadrupole liquid chromatography/mass spectrometry (LC/MS) analysis of the AHLs extracted from the culture supernatant of H. alvei H4 revealed the existence of at least three AHLs: N-hexanoyl-l-homoserine lactone (C6-HSL), N-(3-oxo-octanoyl)-l-homoserine lactone (3-oxo-C8-HSL), and N-butyryl-l-homoserine lactone (C4-HSL). This is the first report of the production of C4-HSL by H. alvei. In order to determine the relationship between the production of AHL by H. alvei H4 and bacterial growth, the ß-galactosidase assay was employed to monitor AHL activity during a 48-h growth phase. AHLs production reached a maximum level of 134.6 Miller unites at late log phase (after 18 h) and then decreased to a stable level of about 100 Miller unites. AHL production and bacterial growth displayed a similar trend, suggesting that growth of H. alvei H4 might be regulated by QS. The effect of AHLs on biofilm formation of H. alvei H4 was investigated by adding exogenous AHLs (C4-HSL, C6-HSL and 3-oxo-C8-HSL) to H. alvei H4 culture. Biofilm formation was significantly promoted (p < 0.05) by 5 and 10 µM C6-HSL, inhibited (p < 0.05) by C4-HSL (5 and 10 µM) and 5 µM 3-oxo-C8-HSL, suggesting that QS may have a regulatory role in the biofilm formation of H. alvei H4.

[Diverse Solvent Effect on Extraction of Chemical Components from Lamiophlomis rotate].

Objective: To investigate the diverse solvent effect on extraction of chemical components from Lamiophlomis rotata. Methods: Based on LC-MS / MS technique, and chromatographic peak comparison, potential chemical components screening and partial least squares-discriminant analysis( PLS-DA) were used to establish a quantitation method for simultaneous determination of chlorogenic acid,forsythoside B,verbascoside,luteoloside,quercetin,luteolin and apigenin. Results: According to the results of PLS-DA and quantitative analysis, methanol, water-saturated n-butanol,75% methanol and 50% methanol showed wider extraction range and higher extraction efficiency to the chemical components of Lamiophlomis rotata. Conclusion: This study offeres references to the extraction technology of Lamiophlomis rotata, and promotes the relative pharmacodynamics study of this medical material.

Single-shot analytical assay based on graphene-oxide-modified surface acoustic wave biosensor for detection of single-nucleotide polymorphisms.

The combination of a surface acoustic wave (SAW) biosensor with graphene oxide (GO) provides a promising perspective for detecting DNA mutation. The GO-modified SAW biosensor was prepared by conjugating GO onto the SAW chip surface via electrostatic interaction. Afterward, the probe was immobilized on the GO surface, and detection of DNA mutation was realized by hybridization. The hybridization with a variety of targets would yield different mass and conformational changes on the chip surface, causing the different SAW signals in real time. A total of 137 clinical samples were detected by a single-shot analytical assay based on GO-modified SAW biosensor and direct sequencing in parallel. The diagnostic performance (both sensitivity and specificity) of the assay was evaluated with the direct sequencing as a reference testing method. The phase-shift value of three genotypes in 137 clinical samples was significantly different (p < 0.001). Furthermore, testing of diagnostic performance yielded diagnostic sensitivity and specificity of 100% and 88.6% for identifying CT and CC genotype, 98.0% and 96.2% for identifying CT and TT genotype, respectively. The single-shot analytical assay based on the GO-modified SAW biosensor could be exploited as a potential useful tool to identify CYP2D6*10 polymorphisms in clinical practice of personalized medicine.

Learning to rapidly re-contact the lost plume in chemical plume tracing.

Maintaining contact between the robot and plume is significant in chemical plume tracing (CPT). In the time immediately following the loss of chemical detection during the process of CPT, Track-Out activities bias the robot heading relative to the upwind direction, expecting to rapidly re-contact the plume. To determine the bias angle used in the Track-Out activity, we propose an online instance-based reinforcement learning method, namely virtual trail following (VTF). In VTF, action-value is generalized from recently stored instances of successful Track-Out activities. We also propose a collaborative VTF (cVTF) method, in which multiple robots store their own instances, and learn from the stored instances, in the same database. The proposed VTF and cVTF methods are compared with biased upwind surge (BUS) method, in which all Track-Out activities utilize an offline optimized universal bias angle, in an indoor environment with three different airflow fields. With respect to our experimental conditions, VTF and cVTF show stronger adaptability to different airflow environments than BUS, and furthermore, cVTF yields higher success rates and time-efficiencies than VTF.

[Study on hepatotoxicity of aqueous extracts of Polygonum multiflorum in rats after 28-day oral administration: cholestasis-related mechanism].

OBJECTIVE: To study the effect of aqueous extracts of Polygonum multiflorum (AEPM) on bile acid synthesis, metabolism and transfer-related molecules in rat liver and the hepatotoxicity-related mechanism of P. multiflorum. METHOD: Sprague-Dawley rats were orally administered with 30, 60 g x kg(-1) APEM once everyday for consecutively 28 days. At the end of the experiment, mRNA and protein expressions of hepatic MRP3, MRP2, BSEP, FXR and CYP7A1 were detected by Real-time PCR and Western blot RESULT: Compared with the normal group, the AEPM high dose group showed significant increases in mRNA expressions of hepatic MRP3 and BSEP of male rats (P < 0.05); AEPM high and low dose groups revealed a notable decrease in mRNA expressions of hepatic FXR (P < 0.05) and remarkable rises in mRNA expressions of hepatic MRP3, MRP2, BSEP, CYP7A1 among female rats (P < 0.05). According to the test results of western blot assay, AEPM high and low dose groups showed consistent changes in protein and mRNA expressions hepatic MRP3, MRP2, BSEP, FXR, CYP7A1. CONCLUSION: The 28 oral administration with AEPM in rats showed a certain effect on expressions of bile acid synthesis, metabolism and transfer-related proteins, as well as cholestatic or choleretic effects in the mRNA expression.

[Effect of complementary treatment of Chinese drugs on myocardial perfusion patients with acute myocardial infarction after coronary intervention: a systematic review].

OBJECTIVE: To systematically review the safety and efficacy of routine Western medicine (WM) plus Chinese drugs for no-flow or slow flow after coronary revascularization. METHODS: CNKI, VIP, CBM, Wanfang Data, PubMed, The Cochrane Library, EMBase, and other relevant databases were electronically searched. Literatures were also manually retrieved from related journals. Randomized control trials of treating no-flow or slow flow patients after coronary revascularization by routine WM treatment plus Chinese drugs were retrieved. The quality of retrieved literature was assessed by methods from Cochrane Handbook. Valid data were extracted and analyzed by meta-analysis using RevMan5. 1.0 Software. Results Totally 5 trials including 526 patients with poor general quality were included. RESULTS: of meta-analyses showed that compared with the routine WM treatment group, additional use of Chinese drugs could improve thrombolysis in myocardial infarction (TIMI) [RR =0. 16, 95% Cl (0.07, 0.34), P < 0.01]; reduce elevated ST segment significantly [RR = 0.59, 95% CI (0.44, 0.79), P = 0. 00031]; in- crease regional myocardial blood flow (P < 0.01) and myocardial perfusion scores (P = 0.0109, P = 0.0115); and improve left ventricular ejection fraction (LVEF) under dobutamine stress state (P = 0.041). Only one trial covered a 6-month follow-up study. There was no statistical difference in the mortality, recurrent myocardial infarction, or revascularization between the two groups. There was no statistical difference in adverse event or safety indicators between the two groups. CONCLUSIONS: Compared with the WM treatment, complementary Chinese drugs could reduce occurrence of no-flow or slow flow after coronary revascularization, and further improve clinical efficacy. But larger and higher quality clinical trials are necessary for further evidence.