Fine particles,less than 2.5 micrometer in diameter (PM2.5),are the main components of inhalable particles.Because of their relatively small size and large surface area,PM2.5 can absorb and retain chemicals,bacteria,viruses and other toxic substances,penetrate deeply into the respiratory tract and easily reach the alveolar ducts,exerting adverse effects on the lungs.PM2.5 can also be absorbed into the bloodstream through alveolar capillaries,causing serious damage to human health.The biological effects produced by PM2.5 are frequently attributed to the oxidative stress induced by intracellular reactive oxygen species alterations and abnormal release of inflammatory mediators closely involved in the development of lung diseases.This review discusses the research advances in relationships between PM2.5 exposure and inflammatory responses and oxidative stress based on experimental researches,in vivo and in vitro studies.Recent epidemiologic investigations have shown associations between increased incidence of respiratory diseases and lung cancer from exposure to low levels of various forms of respirable fibers and particulate matter.In vivo experiments have disclosed the association between PM2.5 exposure and the exacerbation of asthma,bronchitis,chronic obstructive pulmonary disease,and other lung damages.Cell damage mechanisms mainly include alterations of cell signaling pathways,DNA damage,immune injury,autophagy and apoptosis.

OBJECTIVE To investigate the bone development activity and differences in safety of ethanol extract (EE) and water decoction (WD) of Psoralea corylifolia L.efficiently.METHODS Zebrafish larvae were co-exposed to prednisolone 25 μmol· L-1 and different concentrations of EE and WD (0.1,1.0,10 and 100 mg crude drug· L-1),and etidronate disodium (ED) 30 mg·L-1.All these groups were incubated at 28.5℃ until 9 dpf.The medium solution was changed every other day.Zebrafish skeleton at 9 dpf was stained with alizarin red and inspected under an optical microscope,in addition,the death toll and organ toxicity of zebrafish were also observed.The mRNA expression of osteoprotegrin (OPG) and receptor activator of NF-κB ligand (RANKL) in 9 dpf zebrafish were determined with fluorescence quantitative PCR.Zebrafish embryos (1 dpf) were exposed to various concentrations of EE (10,20,30,35,40,50 and 60 mg crude drug· L-1),WD (10,50,100,125,150,175,200 and 500 mg crude drug· L-1),psoralen (12.5,25.0,50.0,100.0,200.0 and 400.0 μmol·L-1) and bakuchiol (1,5,10,25 and 50 μmol· L-1).Embryonic morphology of zebrafish (3 dpf) was inspected with an optical microscope and the death toll of embryos or larvale was counted from 2 dpf to 9 dpf and LC50was calculated.Components of EE and WD ware analyzed by HPLC method.RESULTS Both EE (0.1 mg crude drug· L-1) and WD (1.0 mg crude drug· L-1) groups could increase the staining area and optical density values of zebrafish skeleton compared with prednisolone group (P＜0.01),indicating the increase in bone mineralization;the OPG mRNA expression in both EE and WD (1.0 mg crude drug· L-1) groups increased,while the RANKL mRNA expression decreased (P＜0.01) and the ratio of OPG/RANKL improved obviously (P＜0.01).Embryos exposed to EE,WD,psoralen and bakuchiol showed swelling of the heart and yalk sac,and decrease in GOT.The LC50 of WD and psoralen was 5～8 and 5～21 times that EE and bakuchiol,respectively.The composition and relative content of EE and WD also varied considerably.CONCLUSION Bone development activity and toxicity of EE are both stronger than those of WD.The lipid soluble characteristic components of Psoralea corylifolia L.,may be critical components of toxicity.

OBJECTIVE To investigate the proliferation effect of di(2-ethylhexyl) phthalate (DEHP) on prostate in aged rats at the environmental exposure dose and the possible mechanism.METHODS Thirty-two male Sprague-Dawley rats,aged 1.5 years,were randomly divided into 4 groups (8 rats per group) and treated with DEHP (30,90 and 270 μg· kg-1,ig) and vehicle once daily respectively for 4 weeks.All the animals were anesthetized with pentobarbital sodium and sacrificed on the day subsequent to the last treatment.① Abdominal aortic blood samples were collected,and serum estradiol (E2),testosterone (T) and prolactin (PRL) levels were assayed by ELISA.② The prostate tissues were dissected and categorized into different lobes,weighed and measured.The prostate relative mass was calculated.③ The morphological changes were detected by HE staining and prostate epithelial height was analyzed with microscopic image analysis software.RESULTS Compared with vehicle control group,the prostate relative mass,dorsolateral prostate mass,and dorsolateral prostate index in DEHP 270 μg· kg-1 group were significantly higher (P＜0.05).The height of the ventral prostate epithelium in DEHP 30,90 and 270 μg· kg-1 groups was increased significantly (P＜0.01),so was the height of dorsal prostate epithelium in DEHP 270 μg· kg-1 group (P＜0.01).There were no significant changes in levels of E2,PRL or T in DEHP 30,90 and 270 μg· kg-1 groups,but the ratios of E2/T in DEHP 30 and 270 μμg· kg-1 groups were increased significantly (P＜0.05).CONCLUSION Low-dose DEHP could promote the proliferation of prostatic hyperplasia in the aged rats,which might be associated with the relative levels of endogenous hormone.

OBJECTIVE To investigate the hepatotoxicity mechanisms of ethanol extract of Radix Polygoni Multiflori (RPM) and Radix Polygoni Multiflori Praeparata (RPMP) by high-content screen assay.METHODS HepG2 cells were treated with RPM (10,25,50,100,200 and 300 mg·L-1) and RPMP (10,50,100,300,600 and 1200 mg· L-1) for 3-24 h,respectively.The cell viability was detected by a CellTiter-GloTM luminescent cell viability assay kit.Cell count,reactive oxygen species (ROS),mitochondrial membrane potential (MMP),glutathione (GSH),superoxide dismutase 2 (SOD2),activating transcription factor 4 (ATF4),apoptosis,and cell cycles were investigated by high-content screen assay.Besides,SOD2 and ATF4 levels were confirmed by Western blotting.RESULTS RPM 300 mg· L-1 showed nearly 48 ％ reduction in cell viability compared with cell control (P＜0.01),while RPMP had no significant effect at the same concentration.Both RPM and RPMP decreased the level of MMP (P＜0.05) but incresed levels of GSH,ROS,SOD2 and ATF4 significantly (P＜0.05).Besides,RPM 200 mg· L-1 significantly increased the expression of SOD2 (P＜0.05) at 3 h by high-content screen assay,and the enhanced expression of ATF4 was shown at 6 h (P＜0.05).RPMP 300 mg· L-1 markedly increased the expression of ATF4 at 6 h (P＜0.05),while the expression of SOD2 significantly increased at 24 h (P＜0.05).CONCLUSION Both RPM and RPMP have some cytotoxicity,and the cytotoxicity of RPM is stronger than that of RPMP.The hepatotoxicity mechanisms of RPM and RPMP may be related to cell apoptosis caused by long-term oxidative stress and endoplasmic reticulum stress.

Psychological suboptimal health status is an intermediate state between mental health and mental disease.Without timely intervention,psychological suboptimal health may develop into serious diseases that pose a threat to human physical and mental health,such as depression,anxiety disorders and high blood pressure.This review summarizes the scientific concepts,diagnostic Criteria,intervention and pharmacological research of psychological suboptimal health from the perspective of both modern medicine and traditional Chinese medicine and proposes possible solutions to existing problems in order to contribute to the identification,diagnosis,prevention and treatment of psychological suboptimal health.

OBJECTIVE To establish an in vitro screening system for activin receptor-like kinase 4,5 and 7 (ALK4,ALK5 and ALK7) inhibitors.METHODS The insect expression systems for kinase domain of ALK4,5,7 and Smad2/3 proteins were established using the Bac to Bac baculovirus expression system.The desired proteins were expressed in Sf9 insect cells and purified by GST affinity.The screening system was composed of the kinase,Smad3 protein,ATP as well as the compound.The impact of the compound on the activities of ALK kinase domains was examined by measuring the amount of remnant ATP in the system as ALKs catalyzed the phosphorylation of Smad3 protein and consumed ATP during the process.The screening conditions were optimized,and validation of the screening system was conducted using known ALKs inhibitors.RESULTS All the reconstructed Bacmids were identified to be correct by PCR and restriction enzyme digestion.All the proteins were expressed in Sf9 insect cells after transfection,and purified proteins were achieved by GST affinity purification.For the screening system,the optimized kinase concentration and Smad3 concentration were 10 mg· L-1 and the optimized ATP concentration was 10 nmol·L-1.The Z'factor for ALK4,ALK5,and ALK7 kinase inhibitors screening system was 0.71,0.51 and 0.74,respectively.The well-known ALK inhibitor SB431542 inhibited the catalytic activities of ALK4,ALK5,and ALK7 with IC50 values of 22,188 and 91 nmol· L-1,respectively.CONCLUSION The in vitro screening system for ALK4,ALK5 and ALK7 inhibitors is successfully established.

OBJECTIVE To investigate the protective effect of Sika deer velvet antler protein (SVPr) against renal toxicity in mice and its mechanism.METHODS Forty ICR mice were randomly divided into 5 groups:normal control group (ig distilled water),model group (ig distilled water for 7 d,on the 7th day,ip cisplatin 25 mg·kg-1 to establish the model,afterwards ig distilled water for 3 d) and SVPr 5,10 and 20 mg· kg-1 groups (ig SVPr for 7 d,cisplatin 25 mg· kg-1 was provided 2 h after the last administration,then ig SVPr for 3 d).Testing kits were adopted for the measurement of renal indexes in mice,such as blood urea nitrogen (BUN) and serum creatinine (SCr);oxidative stress indictors of super oxide dismutase (SOD),catalase (CAT),glutathione (GSH) and malondialdehyde (MDA);inflammation indictor levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).Caspase 3,Bax and Bcl-2 were detected via Western blotting,and renal pathological changes were observed by HE staining.RESULTS SVPr (5,10 and 20 mg·kg-1) significantly reduced the levels of SCr,BUN,MDA,TNF-α and IL-6,and the expressions of caspase 3 and Bax (P＜0.05),but increased the activities of SOD,CAT and GSH,and the expression of Bcl-2 (P＜0.05).The renal pathological changes were improved.CONCLUSION SVPr can reduce renal toxicity induced by cisplatin in mice,and the mechanism is probably related to inhibiting oxidative stress or inflammatory reaction and improving cell apoptosis.

OBJECTIVE To explore the effect and mechanisms of baicalein on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice.METHODS BALB/c mice were randomly placed into three groups (n=10):normal control group,TNBS group,and TNBS+baicalein (20 mg· kg-1,once per day) group.Mouse colitis was induced by intrarectal injection of TNBS.Baicalein was administered by oral gavage two days prior to TNBS treatment and until the end of the study (a total of 9 d).The colon length was measured before HE staining was performed for histological damage assessment.The remaining colon pieces were collected to measure the content of tumor necrosis factor-α(TNF-α).Lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage was used as a cell model to determine the content of nitric oxide (NO) in cell culture medium,the mRNA levels of TNF-α,interleukin-6(IL-6),IL-1β,inducible nitric oxide synthase(iNOS),cyclooxygenase 2(COX-2) and monocyte chemoattractant protein-1 (MCP-1),and the protein expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-κB (PI3K/AKT/NF-κB) pathway.RESULTS Baicalein significantly attenuated TNBS-induced colon shortening and histological injury (P＜0.05),which was correlated with the decline in the content of TNF-α in the colon.According to the jn vivo results,baicalein exposure down-regulated the secretion of NO and the mRNA expression of pro-inflammatory mediators (iNOS,COX-2,MCP-1,TNF-α,IL-1β and IL-6) in LPS-stimulated RAW264.7 cells (P＜0.05,P＜0.01).Additionally,the phosphorylation/activation of LPS-stimulated PI3K/AKT/NF-κB pathway was inhibited by baicalein treatment.CONCLUSION The beneficial effect of baicalein in TNBS-induced experimental colitis may be due to PI3K/AKT/NF-κB signaling inhibition.

OBJECTIVE To investigate the dynamic changes in urine metabolic profiles in rats induced by D-galactose (D-Gal),and to study the correlations between the differential metabolites and behavior indicators using the proton nuclear magnetic resonance (1H-NMR)-based metabonomics.METHODS Subcutaneous injection of D-Gal 100 mg· kg-1 for 10 weeks was adopted in the model group.The sample of urine was collected at day 0 (dO),d14,d28,d42,d56 and d70.NMR metabonomics technique was used for acquisition of data,which was analyzed by multivariate statistical analysis.The ability of learning and memory were measured by Morris water maze test from d70.After the behavioral test,the rats were sacrificed and the hippocampus was observed by hematoxylin-eosin staining.RESULTS Principal component analysis (PCA) results revealed that there was considerable difference between the model group and the normal control group at d70.According to the varible importance plot (VIP) calculation and S-plot scores,a total of 12 metabolites were screened and identified as potential biomarkers at d70.The differences of metabolites and Morris water maze test were subjected to correlation analysis,and the results showed that the levels of choline,lactate and dimethylglycine in the model group were significantly increased and negatively correlated with the times of crossing the platform (r =-0.90,-0.50 and-0.52;n=10).Formate was significantly negatively correlated with the time spent in the target area (r =-0.51,n=10),but choline and formate were significantly positively correlated with the escape latency (r =0.72 and 0.53;n=10).However,the levels of creatine and taurine decreased in the model group,which was significantly positively correlated to the times of acrossing platforms (r =0.89 and 0.71;n=10),while alanine was significantly positively correlated to the time spent in the target area(r =0.74,n=10).Taurine,alanine and creatine were significantly negatively correlated with the escape latency (r =-0.66,-0.50 and-0.85;n=10).The correlations between the differential metabolites and the behavioral indicators were further proved.CONCLUSION The metabolic profile changes in urine from D-Gal induced aging model rats are significantly correlated with impairement of ability in learning and memory.1H-NMR metabonomics in urinary metabolic profile changes may be used as an evaluation index in the D-Gal induced aging rats model.

Uihgur medicine is not only an important component of medicine for ethnic minorities in China,but an vital supplement to modern medicine.With the development of modern science,in recent years good progerss has been made in basic sciences and applied research of Uighur medicine.According to the property of Uighur materia medica,medicine can be divided into hot,cold,wet,dry,dry-hot,wet-hot,wet-cold,and dry-cold types,and according to strength of medicinal properties,this medicine is divided into four classes.Most of the drugs of levels 3 and 4 are credited with toxicity.This article summarizes the property and toxicity of medicines of levels 3 and 4 which are includel in Pharmaceutical Standards-Uighur Medicine (1998) edited by the former State Ministry of Health of the People's Republic of China.