Inhibition of mPGES-2 ameliorates NASH by activating NR1D1 via heme.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD), a complex metabolic syndrome, has limited therapeutic options. Microsomal prostaglandin E synthase-2 (mPGES-2) was originally discovered as a prostaglandin E 2 (PGE 2 ) synthase; however, it does not produce PGE 2 in the liver. Moreover, the role of mPGES-2 in NAFLD remains undefined. Herein, we aimed to determine the function and mechanism of mPGES-2 in liver steatosis and steatohepatitis. APPROACH AND RESULTS: To evaluate the role of mPGES-2 in NAFLD, whole-body or hepatocyte-specific mPGES-2-deficient mice fed a high-fat or methionine-choline-deficient diet were used. Compared with control mice, mPGES-2-deficient mice showed reduced hepatic lipid accumulation, along with ameliorated liver injury, inflammation, and fibrosis. Furthermore, the protective effect of mPGES-2 deficiency against NAFLD was dependent on decreased cytochrome P450 4A14 and increased acyl-CoA thioesterase 4 levels regulated by the heme receptor nuclear receptor subfamily 1 group D member 1 (NR1D1), but not PGE 2 . Heme regulated the increased NR1D1 activity mediated by mPGES-2 deficiency. Further, we confirmed the protective role of the mPGES-2 inhibitor SZ0232 in NAFLD therapy. CONCLUSION: Our study indicates the pathogenic role of mPGES-2 and outlines the mechanism in mediating NAFLD, thereby highlighting the therapeutic potential of mPGES-2 inhibition in liver steatosis and steatohepatitis.

circRNA-miRNA-mRNA network analysis to explore the pathogenesis of abnormal spermatogenesis due to aberrant m6A methylation.

Many studies have shown that circRNAs and miRNAs play important roles in many different life processes. However, the function of circRNAs in spermatogenesis remains unknown. Here, we aimed to explore the mechanisms whereby circRNA-miRNAs-mRNAs regulate abnormal m6A methylation in GC-1spg spermatogonia. We first reduced m6A methylation in GC-1spg whole cells after knocking down the m6A methyltransferase enzyme, METTL3. Then, we performed circRNA- and miRNA-seq on GC-1spg cells with low m6A methylation and identified 48 and 50 differentially expressed circRNAs and miRNAs, respectively. We also predicted the targets of the differentially expressed miRNAs by using Miranda software and further constructed the differentially expressed circRNA-differentially expressed miRNA-mRNA ceRNA network. GO analysis was performed on the differentially expressed circRNAs and miRNA-targeted mRNAs, and an interaction network between the proteins of interest was constructed using Cytoscape. The final GO analysis showed that the target mRNAs were involved in sperm formation. Therefore, a PPI network was subsequently constructed and 2 hub genes (H2afx and Dnmt3a) were identified. In this study, we constructed a ceRNA network and explored the regulatory roles of circRNAs and miRNAs in the pathogenesis of abnormal spermatogenesis caused by low levels of methylated m6A. Also, we identified two pivotal genes that may be key factors in infertility caused by abnormal m6A methylation. This may provide some ideas for the treatment of infertility resulting from abnormal spermatogenesis.

Circ2388 regulates myogenesis and muscle regeneration.

The formation of skeletal muscle is a complex process that is coordinated by many regulatory factors, such as myogenic factors and noncoding RNAs. Numerous studies have proved that circRNA is an indispensable part of muscle development. However, little is known about circRNAs in bovine myogenesis. In this study, we discovered a novel circRNA, circ2388, formed by reverse splicing of the fourth and fifth exons of the MYL1 gene. The expression of circ2388 was different between fetal and adult cattle muscle. This circRNA is 99% homologous between cattle and buffalo and is localized in the cytoplasm. Thoroughly, we proved that circ2388 had no effect on cattle and buffalo myoblast proliferation but promotes myoblast differentiation and myotube fusion. Furthermore, circ2388 in vivo stimulated skeletal muscle regeneration in mouse muscle injury model. Taken together, our findings suggest that circ2388 promotes myoblast differentiation and promotes the recovery and regeneration of damaged muscles.

Sleep Deficits Inter-Link Lower Basal Forebrain-Posterior Cingulate Connectivity and Perceived Stress and Anxiety Bidirectionally in Young Men.

BACKGROUND: The basal nucleus of Meynert (BNM), a primary source of cholinergic projections to the cortex, plays key roles in regulating the sleep-wake cycle and attention. Sleep deficit is associated with impairment in cognitive and emotional functions. However, whether or how cholinergic circuit, sleep, and cognitive/emotional dysfunction are inter-related remains unclear. METHODS: We curated the Human Connectome Project data and explored BNM resting state functional connectivities (rsFC) in relation to sleep deficit, based on the Pittsburgh Sleep Quality Index (PSQI), cognitive performance, and subjective reports of emotional states in 687 young adults (342 women). Imaging data were processed with published routines and evaluated at a corrected threshold. We assessed the correlation between BNM rsFC, PSQI, and clinical measurements with Pearson regressions and their inter-relationships with mediation analyses. RESULTS: In whole-brain regressions with age and alcohol use severity as covariates, men showed lower BNM rsFC with the posterior cingulate cortex (PCC) in correlation with PSQI score. No clusters were identified in women at the same threshold. Both BNM-PCC rsFC and PSQI score were significantly correlated with anxiety, perceived stress, and neuroticism scores in men. Moreover, mediation analyses showed that PSQI score mediated the relationship between BNM-PCC rsFC and these measures of negative emotions bidirectionally in men. CONCLUSIONS: Sleep deficit is associated with negative emotions and lower BNM rsFC with the PCC. Negative emotional states and BNM-PCC rsFC are bidirectionally related through poor sleep quality. These findings are specific to men, suggesting potential sex differences in the neural circuits regulating sleep and emotional states.

Aberrant regulation of RNA methylation during spermatogenesis.

Natural modifications of cellular RNA include various chemical modifications, such as N6-methyladenosine (m6 A), which enable the orderly metabolism and function of RNA structural diversity, thereby affecting gene expression. Spermatogenesis is a complex differentiating developmental process, which includes the proliferation of spermatogonial stem cells, spermatocyte meiosis and sperm maturation. Emerging evidence has shown that RNA methylation can influence RNA splicing, exportation and translation, which are controlled in the male germline in order to ensure coordinated gene expression. In this review, we summarize the typical characteristics of different types of RNA methylation during the process of spermatogenesis. In particular, we emphasize the functions of the RNA methylation effectors during the male germ cell development.

[Multi-center randomized double-blind controlled study on children's anorexia (spleen-stomach disharmony) treated with Child Compound Endothelium Corneum].

Child Compound Endothelium Corneum(CCEC)has the effects in invigorating the spleen and appetizing the appetite, and dissolving the accumulation of food. The recent studies have proved that it could improve gastrointestinal motility, restore physiological gastrointestinal peristalsis, increase gastrointestinal digestive motility, and enhance appetite. This trial aimed to evaluate its clinical efficacy and safety in the treatment of children's anorexia(spleen-stomach disharmony). A total of 240 children with anorexia in line with the inclusion and exclusion criteria were selected and randomly divided into experimental group and control group, with 120 in each group. Patients in the experimental group took CCEC and Erpixing Granules simulant. Patients in the control group took Erpi-xing Granules and CCEC simulant. After 21 days of treatment, there was no statistical difference in the recovery rate of anorexia, reduced food intake, eating time, weight change, traditional Chinese medicine syndrome effect, single symptom effect, and trace element Zn recovery rate between the two groups. Based on the non-inferiority test, the experimental group was not inferior to the control group in efficacy. How-ever, the effect of CCEC in reducing appetite in children with anorexia was better than that of control drugs(P<0.05). There was no statistical difference in the incidence of adverse events and adverse reactions between the two groups during the trial. This experiment confirmed the efficacy and safety of CCEC in the treatment of children's anorexia(spleen-stomach disharmony), with a safety and re-liability in clinical application. In addition, it was a better choice for children with anorexia who were mainly manifested by reduced appetite. Meanwhile, compared with granule, chewable tablets were more convenient to take in clinic. Therefore, the efficacy and safety of CCEC for the treatment of children's anorexia(spleen-stomach disharmony) were not inferior to those of Erpixing Granules, with a safety and reliability in clnic. However, due to the small sample size of this trial, the efficacy results only show a trend. It is suggested to further carry out a large-sample-size clinical study to define the clinical advantages of CCEC.

Preventive and Therapeutic Effect of Ganoderma (Lingzhi) on Liver Injury.

Ganoderma lucidum (G. lucidum, Lingzhi) has a wide range of hepatoprotective effects. Its bioactive substances include triterpenoids, polysaccharides, sterols, steroids, peptides, and other bioactive ingredients. Based on our research and other references, this chapter discusses the hepatoprotective effects of G. lucidum in different liver diseases, including hepatocellular carcinoma, nonalcoholic liver disease, alcoholic liver disease, hepatitis B, inflammation, fibrosis, and toxicant-induced liver injury. The liver protective mechanisms of G. lucidum vary from diseases to diseases. This chapter will summarize the hepatoprotective effects of G. lucidum on different liver injury and their clinical applications.

Preventive and Therapeutic Effect of Ganoderma (Lingzhi) on Renal Diseases and Clinical Applications.

The mechanisms of kidney diseases, such as acute kidney injury (AKI) and chronic kidney disease (CKD), have been intensively studied. Nonetheless, the morbidity and mortality of AKI and CKD increased in recent years. Recently, natural products have been increasingly recognized as an alternative source for treating renal diseases on account of the conventional experience and the multi-target characteristics. Ganoderma lucidum (G. lucidum, Lingzhi) has been used for centuries as nutraceuticals and alternative medicine to improve health and to treat numerous diseases. Benefiting from various biological activities, such as anti-oxidation, anti-inflammation, anti-tumor growth and metastasis, etc., G. lucidum has been proved to exhibit significant role in preventing and treating various kidney diseases. In this chapter, we review certain researches and provide comprehensive insights into the renoprotective effects of G. lucidum.

Ganoderma Lucidum Polysaccharide Peptide Alleviates Hepatoteatosis via Modulating Bile Acid Metabolism Dependent on FXR-SHP/FGF.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) encompasses a series of pathologic changes ranging from steatosis to steatohepatitis, which may progress to cirrhosis and hepatocellular carcinoma. The purpose of this study was to determine whether ganoderma lucidum polysaccharide peptide (GLPP) has therapeutic effect on NAFLD. METHODS: Ob/ ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD. Key metabolic pathways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blot. Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD. RESULTS: GLPP administrated for a month alleviated hepatosteatosis, dyslipidemia, liver dysfunction and liver insulin resistance. Pathways of glycerophospholipid metabolism, fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD. Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1, CYP8B1, FXR, SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice. Besides, GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c, FAS and ACC via a FXR-SHP dependent mechanism. Additionally, GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepatocytes induced by oleic acid and palmitic acid. CONCLUSION: GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway, which finally inhibits fatty acid synthesis, indicating that GLPP might be developed as a therapeutic drug for NAFLD.

Elevated urinary urea by high-protein diet could be one of the inducements of bladder disorders.

BACKGROUND: Previous work found that urea accumulation in urothelial cells caused by urea transporter B knockout led to DNA damage and apoptosis that contributed to the carcinogenesis. The purpose of this study is to explore the potential connection between high urinary urea concentration and the bladder disorders. METHODS: A high protein diet rat model was conducted by feeding with 40 % protein diet. In-silico modeling and algorithm, based on the results of microarray and proteomics from the bladder urothelium, were used for the reconstruction of accurate cellular networks and the identification of novel master regulators in the high-protein diet rat model. Pathway and biological process enrichment analysis were used to characterize predicted targets of candidate mRNAs/proteins. The expression pattern of the most significant master regulators was evaluated by qPCR and immunohistochemistry. RESULTS: Based on the analysis of different expressed mRNAs/proteins, 15 significant ones (CRP, MCPT2, MCPT9, EPXH2, SERPING1, SRGN, CDKN1C, CDK6, CCNB1, PCNA, BAX, MAGEB16, SERPINE1, HSPA2, FOS) were highly identified and verified by qPCR and immunohistochemistry. They were involved in immune and inflammatory response, cell cycle arrest, apoptosis and pathways in cancer. These abnormally activated processes caused the bladder interstitial congestion and inflammatory infiltrates under the thinner urothelium, cell desquamation, cytoplasm vacuolization, nucleus swelling and malformation in the high-protein diet group. CONCLUSIONS: We provided evidences that high urinary urea concentration caused by high-protein diet might be a potential carcinogenic factor in bladder.

Association between intake of antioxidants and pancreatic cancer risk: a meta-analysis.

We conducted a meta-analysis to systematically evaluate the association between antioxidants intake and pancreatic cancer risk. Relevant articles were retrieved from PUBMED and EMBASE databases and standard meta-analysis methods were applied. Finally a total of 18 studies were included. Comparing the highest with lowest categories, higher dietary intakes of selenium, vitamin C, vitamin E, ß-carotene and ß-cryptoxanthin were significantly associated with reduced pancreatic cancer risk (for selenium, pooled OR = 0.47, 95%CI 0.26-0.85; for vitamin C, pooled OR = 0.68, 95%CI 0.57-0.80; for vitamin E, pooled OR = 0.70, 95%CI 0.62-0.81; for ß-carotene, pooled OR = 0.74, 95%CI 0.56-0.98; for ß-cryptoxanthin, pooled OR = 0.70, 95%CI 0.56-0.88). Lycopene intake was marginally associated with pancreatic cancer risk (pooled OR = 0.85, 95%CI 0.73-1.00), while no significant association was observed for α-carotene, lutein and zeaxanthin. In summary, higher dietary intake of selenium, vitamin C, vitamin E, ß-carotene and ß-cryptoxanthin was inversely associated with pancreatic cancer risk.

Propofol Prevents Renal Ischemia-Reperfusion Injury via Inhibiting the Oxidative Stress Pathways.

BACKGROUND/AIMS: Renal ischemia/reperfusion injury (IRI) is a risk for acute renal failure and delayed graft function in renal transplantation and cardiac surgery. The purpose of this study is to determine whether propofol could attenuate renal IRI and explore related mechanism. METHODS: Male rat right kidney was removed, left kidney was subjected to IRI. Propofol was intravenously injected into rats before ischemia. The kidney morphology and renal function were analyzed. The expression of Bax, Bcl-2, caspase-3, cl-caspase-3, GRP78, CHOP and caspase-12 were detected by Western blot analysis. RESULTS: IR rats with propofol pretreatment had better renal function and less tubular apoptosis than untreated IR rats. Propofol pretreated IR rats had lower Bax/Bcl-2 ratio and less cleaved caspase-3. The protein expression levels of GRP78, CHOP and caspase-12 decreased significantly in propofol pretreated IR rats. In vitro cell model showed that propofol significantly increased the viability of NRK-52E cells that were subjected to hypoxia/reoxygenation (H/R) in a dose-dependent manner. The effect of propofol on the expression regulation of Bax, Bcl-2, caspase-3, GRP78, CHOP was consistent in both in vitro and in vivo models. CONCLUSION: Experimental results suggest that propofol prevents renal IRI via inhibiting oxidative stress.

Effect of minimizing amount of template by addition of macromolecular crowding agent on preparation of molecularly imprinted monolith.

One of the main challenges in the preparation of molecularly imprinted polymers (MIPs) is the substantial initial amount of template needed because of the requirement of high load capacities for most applications. A new strategy of macromolecular crowding was suggested to solve this problem by reducing the amount of template in the polymerization recipe. In a ternary porogenic system of polystyrene (PS) (crowding agent), tetrahydrofuran, and toluene, an imprinted monolithic column with high porosity and good permeability was synthesized using a mixture of ellagic acid (template), acrylamide, and ethylene glycol dimethacrylate. The effect of polymerization factors, including monomer-template molar ratio and the molecular weight and concentration of PS, on the imprinting effect of the resulting MIP monoliths was systematically investigated. At a high ratio of monomer-template (120:1), the greatest imprinting factor of 32.4 was obtained on the MIP monolith with the aid of macromolecular crowding agent. The PS-based imprinted monolith had imprinting even at the extremely high ratio of functional monomer to template of 1510:1. Furthermore, an off-line solid-phase extraction based on the ground MIP was conducted, and the purification recovery of ellagic acid from pomegranate-rind extract was up to 80 %. In conclusion, this approach based on macromolecular crowding is simple, and is especially valuable for those applications of MIP preparation for which a rare template is used.

Binding characteristics and interactive region of 2-phenylpyrazolo[1,5-c]quinazoline with DNA.

The interaction between 2-phenylpyrazolo[1,5-c]quinazoline (PQ) and DNA under physiological conditions was investigated using multi-spectroscopic techniques, atomic force microscopy and gel electrophoresis. The thermodynamic parameters were estimated and were discussed in detail. The results of fluorescence-quenching experiments indicated that the main interactive force between PQ and DNA was a hydrophobic interaction and that it was a static quenching process. Potassium iodide and single-strand (ss)DNA quenching studies, together with circular dichroism spectra implied groove binding of PQ with DNA. Atomic force microscopy and gel electrophoresis experiments suggested that there were no major conformational changes in DNA upon interaction with PQ. In addition, UV/vis absorption titration of DNA bases confirmed that PQ bound with DNA mainly through a minor groove interaction and preferentially interacted with adenine and thymine. We anticipate that this work will provide useful information for the application of quinazoline derivatives in the fields of medicinal and pharmaceutical chemistry.

Potassium humate supplementation improves photosynthesis and agronomic and yield traits of foxtail millet.

Foxtail millet is a highly nutritious crop, which is widely cultivated in arid and semi-arid areas worldwide. Humic acid (HA), as a common plant growth regulator, is used as an organic fertilizer and feed additive in agricultural production. However, the impact of potassium humate KH on the photosynthetic rate and yield of foxtail millet has not yet been studied. We explored the effects of KH application on the morphology, photosynthetic ability, carbon and nitrogen metabolism, and yield of foxtail millet. A field experiment was performed using six concentrations of KH (0, 20, 40, 80, 160, and 320 kg ha-1) supplied foliarly at the booting stage in Zhangza 10 cultivar (a widely grown high-yield variety). The results showed that KH treatment increased growth, chlorophyll content (SPAD), photosynthetic rate (Pn), transpiration rate (Tr), and stomatal conductance (Gs). In addition, soluble protein content, sugar content, and nitrate reductase activity increased in KH-treated plants. With increased KH concentration, the effects became more evident and the peak values of each factor were achieved at 80 kg ha-1. Photosynthetic rate showed significant correlation with SPAD, Tr, Gs, and soluble protein content, but was negatively correlated with intercellular CO2 concentration. Compared to that of the control, the yield of foxtail millet under the T2, T3, T4, and T5 (40, 80, 160, and 320 kg ha-1 of KH) treatments significantly increased by 6.0%, 12.7%, 10.5%, and 8.6%, respectively. Yield exhibited a significant positive correlation with Tr, Pn, and Gs. Overall, KH enhances photosynthetic rate and yield of foxtail millet, therefore it may be conducive to stable millet production. These findings may provide a theoretical basis for the green and efficient production of millet fields.

Genetic or pharmacologic blockade of mPGES-2 attenuates renal lipotoxicity and diabetic kidney disease by targeting Rev-Erbα/FABP5 signaling.

Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and no specific drugs are clinically available. We have previously demonstrated that inhibiting microsomal prostaglandin E synthase-2 (mPGES-2) alleviated type 2 diabetes by enhancing ß cell function and promoting insulin production. However, the involvement of mPGES-2 in DKD remains unclear. Here, we aimed to analyze the association of enhanced mPGES-2 expression with impaired metabolic homeostasis of renal lipids and subsequent renal damage. Notably, global knockout or pharmacological blockage of mPGES-2 attenuated diabetic podocyte injury and tubulointerstitial fibrosis, thereby ameliorating lipid accumulation and lipotoxicity. These findings were further confirmed in podocyte- or tubule-specific mPGES-2-deficient mice. Mechanistically, mPGES-2 and Rev-Erbα competed for heme binding to regulate fatty acid binding protein 5 expression and lipid metabolism in the diabetic kidney. Our findings suggest a potential strategy for treating DKD via mPGES-2 inhibition.

Buffalo bbu-miR-493-5p Promotes Myoblast Proliferation and Differentiation.

In recent years, the meat and dairy value of buffaloes has become a major concern in buffalo breeding, and the improvement of buffalo beef quality is key to protecting buffalo germplasm resources and solving the problem of beef supply. MiRNAs play a significant role in regulating muscle development. However, the precise mechanism by which they regulate the development of buffalo skeletal muscles remains largely unexplored. In this study, we examined miRNA expression profiles in buffalo myoblasts during the proliferation and differentiation stages. A total of 177 differentially expressed miRNAs were identified, out of which 88 were up-regulated and 89 down-regulated. We focused on a novel miRNA, named bbu-miR-493-5p, that was significantly differentially expressed during the proliferation and differentiation of buffalo myoblasts and highly expressed in muscle tissues. The RNA-FISH results showed that bbu-miR-493-5p was primarily located in the cytoplasm to encourage buffalo myoblasts' proliferation and differentiation. In conclusion, our study lays the groundwork for future research into the regulatory role of miRNAs in the growth of buffalo muscle.

A Circular RNA Generated from Nebulin (NEB) Gene Splicing Promotes Skeletal Muscle Myogenesis in Cattle as Detected by a Multi-Omics Approach.

Cattle and the draught force provided by its skeletal muscle have been integral to agro-ecosystems of agricultural civilization for millennia. However, relatively little is known about the cattle muscle functional genomics (including protein coding genes, non-coding RNA, etc.). Circular RNAs (circRNAs), as a new class of non-coding RNAs, can be effectively translated into detectable peptides, which enlightened us on the importance of circRNAs in cattle muscle physiology function. Here, RNA-seq, Ribosome profiling (Ribo-seq), and peptidome data are integrated from cattle skeletal muscle, and detected five encoded peptides from circRNAs. It is further identified and functionally characterize a 907-amino acids muscle-specific peptide that is named circNEB-peptide because derived by the splicing of Nebulin (NEB) gene. This peptide localizes to the nucleus and cytoplasm and directly interacts with SKP1 and TPM1, key factors regulating physiological activities of myoblasts, via ubiquitination and myoblast fusion, respectively. The circNEB-peptide is found to promote myoblasts proliferation and differentiation in vitro, and induce muscle regeneration in vivo. These findings suggest circNEB-peptide is an important regulator of skeletal muscle regeneration and underscore the possibility that more encoding polypeptides derived by RNAs currently annotated as non-coding exist.

Rapid preparation of molecularly imprinted polymer by frontal polymerization.

Frontal polymerization was successfully applied, for the first time, to obtain molecularly imprinted polymers (MIPs). The method provides a solvent-free polymerization mode, and the reaction can be completed in 30 min. By this approach, MIPs were synthesized using a mixture of levofloxacin (template), methacrylic acid, and divinylbenzene. The effect of template concentration and the amount of comonomer on the imprinting effect of the resulting MIPs was investigated. The textural and morphological parameters of the MIP particles were also characterized by mercury intrusion porosimetry, nitrogen adsorption isotherms, and scanning electron microscopy, providing evidence concerning median pore diameter, pore volumes, and pore size distributions. The levofloxacin-imprinted polymer formed in frontal polymerization mode showed high selectivity, with an imprinting factor of 5.78. The results suggest that frontal polymerization provides an alternative means to prepare MIPs that are difficult to synthesize and may open up new perspectives in the field of MIPs.

Drug-drug interaction of rabeprazole and clopidogrel in healthy Chinese volunteers.

PURPOSE: This study was aimed to determine the impact of rabeprazole (RBRZ) on the antiplatelet efficacy of clopidogrel (CPG) in healthy Chinese volunteers, and further to predict the effect of CYP2C19 genetic polymorphism on the efficacy of rabeprazole and clopidogrel. METHODS: The open-label, two period cross-over study was conducted in 20 healthy Chinese subjects with different CYP2C19 genotypes receiving clopidogrel, rabeprazole or the two drugs, respectively. All the volunteers were divided into two groups, poor metabolizers (PMs) and extensive metabolizers (EMs), depending on CYP2C19 genotypes. Blood samples were collected at baseline and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 h after administration. The plasma concentrations of rabeprazole and clopidogrel were analyzed by LC-MS/MS and ADP-induced platelet aggregation was detected by the optical turbidimetric method. RESULTS: There were no significant differences in the mean plasma concentration-time curves of clopidogrel (CPG), the inactive metabolite clopidogrel carboxylic acid (CPG-CA), the active metabolite clopidogrel-MP-Derivative (MP-AM), and rabeprazole (RBRZ) according to the co-administration of CPG and RBRZ. There were no major changes in the pharmacokinetics of CPG and RBRZ. The maximal ADP-induced platelet aggregation (2 µmol/L) was decreased in EMs compared with PMs. CONCLUSION: Co-administration of rabeprazol and clopidogrel did not affect the antiplatelet efficacy of clopidogrel. The CYP2C19 genetic polymorphism may impact the efficacy of clopidogrel.