Pulmonary inflammation caused by cigarette smoke combined with lipopolysaccharide up-regulated OATP2B1 in rat lung tissue and pulmonary epithelial cells.

Organic anion transport polypeptide 2B1 (OATP2B1), as an uptake transporter, is involved in the transport of many related substrate drugs and endogenous substances in the lungs. A large amount of data shows that cigarette smoke plays an important role in the occurrence and development of lung diseases such as chronic obstructive pulmonary disease (COPD), asthma and bronchitis. However, the effect of cigarette smoke combined with lipopolysaccharide-induced pulmonary inflammation on the expression of OATP2B1 is not clear. In this study, we used cigarette smoke combined with lipopolysaccharide to establish a lung inflammation model in vivo and in vitro to explore the effect of inflammation on the expression of OATP2B1. Our study found that cigarette smoke combined with lipopolysaccharide-induced pulmonary inflammation upregulated the mRNA and protein expression of OATP2B1 and related inflammatory factors, and the expression level of related proteins was higher with the aggravation of inflammation. The experimental results of animals in vivo were consistent with those of cells in vitro. In summary, these findings provide a model and basis for a follow-up study of the mechanism of OATP2B1 in pulmonary inflammation.

Cigarette smoke extract combined with LPS reduces ABCA3 expression in chronic pulmonary inflammation may be related to PPARγ/ P38 MAPK signaling pathway.

ABCA3 (ATP-binding cassette class A3) is a transmembrane transporter that plays a positive role in chronic pulmonary inflammation by regulating lipid metabolism. However, it is not completely clear whether ABCA3 and its signaling factors are involved in chronic pulmonary inflammation induced by the combination of CSE (cigarette smoke extract) and LPS (lipopolysaccharide). In this study, we used the method of combining CSE and LPS which was widely used to study lung inflammation-related diseases and has been proven effective in our group's studies to create in vivo and in vitro pulmonary inflammation models. The result showed that, after CSE in combination with LPS treatment, ABCA3 expression was downregulated in rat lung in vivo and in a human alveolar cell line in vitro. ABCA3 expression was upregulated, and related inflammatory factors were downregulated in the state of overexpression of PPARγ or inhibition of the p38 MAPK pathway, while PPARγ deletion or MAPK14 overexpression showed the opposite results. The level of PPARγ remained unchanged, and the expression of ABCA3 was upregulated in the state of the p38 MAPK pathway was inhibited under overexpression of PPARγ. These results indicate that CSE combined with LPS can result in downregulation of ABCA3 under conditions of inflammation, and that the p38 MAPK signaling pathway mediated by PPARγ can regulate the expression changes of ABCA3, thus providing new targets for treating chronic pulmonary inflammation.

The changes of MRP2 expression in three kinds of pulmonary inflammation models: the downregulation occurred in cigarette smoke extract (CSE) stimulation group and CSE plus LPS stimulation group, unchanged in LPS stimulation group.

The transporter multidrug resistance protein 2 (MRP2) can transport some tobacco carcinogens and plays an important role in the transport of mediators related to pulmonary inflammatory diseases. However, it is not fully understood whether the pulmonary inflammation caused by cigarette smoke extract (CSE) and lipopolysaccharide (LPS) is related to the regulation of MRP2. In this study, CSE and LPS were used alone and in combination as stimuli to induce pulmonary inflammation. In addition, the establishment of a pulmonary inflammation model was verified by animal experiments in vivo. We found that compared with those in the control group, the expression of MRP2 protein was downregulated and the expression of inflammatory cytokines was upregulated in pulmonary inflammation in the CSE group and the CSE combined with LPS group. However, there was almost no change in the expression of MRP2 stimulated by LPS alone. Our results show that CSE and CSE combined with LPS downregulate the expression of MRP2 under inflammatory conditions, while LPS has almost no effect on the expression of MRP2 under inflammatory conditions. The in vivo experimental results of CSE combined with LPS were consistent with the cellular results of CSE combined with LPS, which provides a model and basis for other studies of the role of MRP2 in pulmonary inflammation.

Pharmacokinetic Interaction of astragaloside IV with atractylenolide I and prim-O-glucosylcimifugin in male Sprague Dawley rats.

Astragaloside IV, atractylenolide I, and prim-O-glucosylcimifugin are main medicinal components of the traditional Chinese medicine prescription Yu-ping-feng which is composed of three herbs: Astragalus membranaceus, Atractylodes macrocephala, and Saposhnikovia divaricata. This study is aimed to assess the influence of atractylenolide I and prim-O-glucosylcimifugin on the pharmacokinetic profile of astragaloside IV so as to investigate the pharmacokinetic mechanisms of the Yu-ping-feng prescription. Fifteen Sprague Dawley rats were randomized to three groups; astragaloside IV, astragaloside IV plus atractylenolide I, and a combination of astragaloside IV, atractylenolide I, and prim-O-glucosylcimifugin were respectively administered to rats of these three groups via intragastric gavage. Serum samples were collected at different times after drug administration, and serum concentrations of astragaloside IV and atractylenolide I were simultaneously detected using HPLC-electrospray ionization-MS. Compared with administration of astragaloside IV alone, concentrations of astragaloside IV in the serum were significantly increased when it was given in combination with atractylenolide I or atractylenolide I+prim-O-glucosylcimifugin, with higher values for Cmax (p = 0.019 and p = 0.033 compared with astragaloside IV + atractylenolide I and astragaloside IV + atractylenolide I + prim-O-glucosylcimifugin groups, respectively) and AUC (p = 0.0052 and p = 0.0047 compared with astragaloside IV + atractylenolide I and astragaloside IV + atractylenolide I + prim-O-glucosylcimifugin groups, respectively). Improvement in mean oral Cmax and mean systemic serum exposure because of the pharmacokinetic interaction between astragaloside IV and atractylenolide I might explain the rationale for the use of multiple herbs in Yu-ping-feng and of combinations of A.membranaceus and A. macrocephala.

Pharmacokinetic-pharmacodynamic evaluation of the major component astragaloside IV on the immunomodulatory effects of Yu-ping-feng prescription.

Yu-ping-feng decoction (YPF), a traditional Chinese medicine (TCM) prescription, is widely used to treat some respiratory tract diseases. This study was aimed to set up a pharmacokinetic-pharmacodynamic (PK-PD) model to assess dose-effect relationships for immunomodulatory effects of YPF in rats and to clarify compatibility mechanisms for TCM prescription system. Serum samples taken after YPF administration were tested on spleen cells of rats in vitro and proliferation ratio of spleen cells was used as end points to evaluate pharmacodynamic properties of immunoregulatory effects of YPF prescription. And with a HPLC-MS method, concentrations of Astragaloside IV (AS), a main component of YPF, were determined to achieve pharmacokinetic parameters after administration of a simplified prescription which is composed with AS, Atractylenolide I and Prim-O-glucosylcimifugin which are representative components of YPF. A plot of serum AS concentrations versus time and effects showed that there was a correlated relationship between AS concentrations and effects of YPF, and the concentration-response curve which was based on an E max model showed a counterclockwise hysteresis manner. A PK-PD model with Sheiner's method was used to describe time course of AS concentration in blood compartment and effect compartment, and main parameters with the PK-PD model were calculated. These results showed that there is a symmetry relationship between serum AS concentrations and responses of serum containing medicine of YPF prescription, which means that AS plays an important role in immunoregulatory effects of YPF. And the investigation on dose-effect relationships has displayed a feasible method to clarify mechanisms of combination for TCM prescriptions.

20-Hydroxytetraenoic acid induces hepatic fibrosis via the TGF-ß1/Smad3 signaling pathway.

Hepatic fibrosis is caused by excessive accumulation of extracellular matrix (ECM) due to repeated liver injury. Hepatic stellate cells (HSCs) play a key role in the pathogenesis and progression of hepatic fibrosis. A study showed that CYP4A14 gene defect can inhibit hepatic fibrosis, but the specific mechanism was not clear. In this experiment, patients with hepatic fibrosis, LX-2 cells (a human HSCs line), and mice with liver fibrosis induced by carbon tetrachloride (CCl4) were used to study the effect of 20-Hydroxytetraenoic acid (20-HETE), one of the main metabolites of arachidonic acid (AA) catalyzed by CYP4A enzyme, on hepatic fibrosis and its mechanism. Our experimental results showed that the 20-HETE of patients with hepatic fibrosis is significantly higher than that of normal people and is closely related to the degree of fibrosis. 20-HETE could induce activation of LX-2 cells and 20-HETE antagonist could inhibit the induction of 20-HETE. 20-HETE was significantly increased in CCl4-induced liver fibrosis mice and inhibition of 20-HETE production could attenuate hepatic fibrosis. 20-HETE induced hepatic fibrosis mainly via the TGF- ß1/Smad3 signal pathway. In conclusion, the results suggest that 20-HETE plays an important role in hepatic fibrosis and may be a possible target for the clinical treatment of hepatic fibrosis.

[Analysis of correlation between maxillary molars and maxillary sinus mucosal thickening].

PURPOSE: To investigate the influence of maxillary molars on the thickening of maxillary sinus mucosa by cone-beam CT (CBCT). METHODS: A total of 72 patients with periodontitis were included in the study and 137 cases of maxillary sinus were evaluated using CBCT for the following parameters: location, tooth, maximal mucosal thickness, alveolar bone loss, vertical intrabony pockets and minimal residual bone height. The maxillary sinus mucosal thickness ≥2 mm was defined as mucosal thickening. The parameters that could influence the dimensions of the maxillary sinus membrane were assessed. The data were analyzed using univariate analysis and binary logistic regression by SPSS 25.0 software package. RESULTS: Mucosal thickening was present in 56.2% of 137 cases and increased in frequency as the alveolar bone loss of the corresponding molar progressed from mild (21.1%) to moderate (56.1%) to severe (69.2%), and the risk of maxillary sinus mucosal thickening increased by 6-7 times (moderate OR=7.13, 95%CI: 1.37-37.21; severe OR=6.29, 95%CI: 1.06-37.37). The severity of vertical intrabony pockets was correlated with the presence of mucosal thickness (no intrabony pockets 38.7%; type Ⅰ 63.4%; type Ⅱ 79.4%), with an increased risk of maxillary sinus mucosal thickening (type Ⅰ OR=3.72, 95%CI: 1.01-13.70; type Ⅱ OR=5.39, 95%CI: 1.15-25.30). The minimal residual bone height was negatively correlated with the presence of mucosal thickness(≤4 mm OR=99.00, 95%CI: 17.42-562.79). CONCLUSIONS: Alveolar bone loss, vertical intrabony pockets and the minimal residual bone height in maxillary molars were significantly associated with mucosal thickening of the maxillary sinus.

IL-8 exacerbates CCl4-induced liver fibrosis in human IL-8-expressing mice via the PI3K/Akt/HIF-1α pathway.

Liver fibrosis is an excessive accumulation of extracellular matrix (ECM) due to chronic liver injury. In recent years, the mechanism of liver fibrosis has been extensively studied. Hepatic stellate cells (HSCs) play an important role in the occurrence and development of liver fibrosis because activated hepatic stellate cells could synthesize a large number of ECM and thus participate in the process of liver fibrosis. Interleukin-8 (IL-8) (deletion in mice) is a versatile chemokine that promotes inflammation and affects cell growth by activating related pathways and plays an important role in the development and progression of a variety of diseases. Notably, the expression level of IL-8 was significantly higher in patients with liver fibrosis, suggesting that it may be related to the pathogenesis of liver fibrosis. In this study, we used hydrodynamic injection to deliver the lentiviral vector LV5-hIL-8 into mice. We found that hIL-8 could aggravate carbon tetrachloride (CCl4)-induced liver fibrosis through the PI3K/Akt/HIF-1α pathway. It is characterized by excessive accumulation of ECM as well as a significant increase in markers of liver injury. In addition, in PDGF-induced HSCs, we also demonstrated that hIL-8 could aggravate ECM accumulation through the PI3K/Akt/HIF-1α pathway. In conclusion, the results of this study on hIL-8 may help to identify potential targets for the clinical treatment of liver fibrosis.

Cigarette smoke extract combined with LPS down-regulates the expression of MRP2 in chronic pulmonary inflammation may be related to FXR.

The transporter multidrug resistance protein 2 (MRP2) plays an important role in chronic pulmonary inflammation by transporting cigarette smoke and other related inflammatory mediators. However, it is not completely clear whether pulmonary inflammation caused by cigarette smoke extract (CSE) and lipopolysaccharide (LPS) is related to MRP2 and its signal factors. In this study, CSE combined with LPS was used to establish an inflammation model in vivo and in vitro. We found that compared with the control group, after CSE combined with LPS treatment, the expression of MRP2 in rat lung tissue in vivo and human alveolar cell line in vitro was down-regulated, while the expression of inflammatory factors was up-regulated. Through silencing and overexpression of FXR, it was found that silent FXR could down-regulate MRP2 and up-regulate the expression of inflammatory factors. On the contrary, overexpression of FXR could up-regulate MRP2 and down-regulate the expression of inflammatory factors. Our results show that CSE combined with LPS can down-regulate the expression of MRP2 under inflammatory conditions, and the down-regulation of MRP2 expression may be achieved partly through the FXR signal pathway.

DJ-1 modulates Nrf2-mediated MRP1 expression by activating Wnt3a/ß-catenin signalling in A549 cells exposed to cigarette smoke extract and LPS.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by airway obstruction and abnormal inflammatory responses. Multidrug resistance-related protein 1 (MRP1) can reduce lung inflammation and damage by excreting various toxic exogenous substances and certain pro-inflammatory molecules. AIMS: We studied whether DJ-1 modulates nuclear factor erythroid 2-related factor 2 (Nrf2) by activating the Wnt3a/ß-catenin signalling pathway to further regulate MRP1 expression and pulmonary antioxidant defences in alveolar epithelial (A549) cells treated with smoke extract (CSE) and lipopolysaccharide (LPS). MAIN METHODS: Marker expression was studied by western blot analysis, quantitative real-time PCR and immunofluorescence staining of A549 cells. KEY FINDINGS: A549 cells exposed to CSE and LPS showed downregulation of DJ-1, Wnt3a, MRP1 and haem oxygenase-1 (HO-1) and upregulation of inflammatory factors. Additionally, Nrf2 protein levels were significantly decreased, while there was no change in Nrf2 mRNA levels. Overexpression of DJ-1 and Wnt3a activated Nrf2 signalling, increased MRP1 and HO-1 levels and decreased IL-6 protein expression, while knockdown of DJ-1 and Wnt3a had the opposite effects. Furthermore, DJ-1 overexpression and DJ-1 knockdown increased and decreased, respectively, the levels of Wnt3a and ß-catenin. Interestingly, Nrf2 and Wnt3a deficiency reduced the protective effects of Wnt3a and DJ-1, respectively, in A549 cells. However, the levels of DJ-1 and Wnt3a were not altered by Wnt3a and Nrf2 deletion, respectively. SIGNIFICANCE: In A549 cells treated with CSE and LPS, DJ-1 regulates Nrf2-mediated MRP1 expression and antioxidant defences by activating the Wnt3a/ß-catenin signalling pathway. These findings may provide potential therapeutic targets for COPD intervention.

[Relationship between tongue presentations and serum level of C-reactive protein in patients with acute cerebral infarction].

OBJECTIVE: To investigate the relationship between tongue presentations and the serum level of C-reactive protein (CRP) in patients with acute cerebral infarction (ACI). METHODS: Tongue presentations of 200 incipient unilateral ACI patients were observed, their serum CRP level was determined, and the relationship between the two entries was analyzed. RESULTS: Serum level of CRP in patients with thick tongue coating were significantly more than those with thin coating (117 cases vs. 73 cases); tongue coating was greasy in 149 patients and un-greasy in 51 patients. Spearman correlation analysis showed that the serum level of CRP was positively correlated with the thickness of tongue coating (r = 0.186, P = 0.008); also with the greasy degree. The difference of CRP levels in patients with different color and dryness of tongue was insignificant statistically (P > 0.05). CONCLUSION: Correlation between tongue presentations and serum CRP level is possibly existed in patients with ACI.

LPS-induced inflammation delays the transportation of ASP+ due to down-regulation of OCTN1/2 in alveolar epithelial cells.

Organic cation transporters (OCTNs) can significantly affect drug disposition in alveolar epithelial cells (A549), but this process is not well understood. We investigated the expression and function of OCTN1/2 in A549 cells under different inflammatory status to examine pulmonary drug distribution. This experiment used lipopolysaccharide (LPS)-treated A549 cells to mimic inflammation in alveolar epithelial cells, and the expression of OCTN1/2, interleukin-6 (IL6), IL18, IL1ß and tumour necrosis factor-alpha (TNF-α) was investigated by western blot and quantitative real-time PCR (qRT-PCR). The fluorescent compound 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP+) was chosen as a probe to study the activity of OCTN1/2. OCTN1/2 down-regulation induced by LPS was more pronounced than that in normal control (NC) groups. Experiments further detected the release of inflammatory factors that revealed a negative correlation between OCTN1/2 expression and inflammation secretion in human alveolar epithelial cells exposed to different concentrations of LPS. The Michaelis constant (Km) and apparent permeability coefficient (Papp) of ASP+ were also decreased significantly. Our results thus show that LPS-induced inflammation could inhibit the expression and activity of OCTN1/2 in vitro and reduce the distribution of inhaled medicine in pulmonary diseases.

Cigarette smoke extract combined with lipopolysaccharide reduces OCTN1/2 expression in human alveolar epithelial cells in vitro and rat lung in vivo under inflammatory conditions.

Organic cation transporter 1/2 (OCTN1/2) play important roles in the transport of drugs related to pulmonary inflammatory diseases. Nevertheless, the involvement of inflammation induced by cigarette smoke extract (CSE) combined with lipopolysaccharide (LPS) in the regulation of OCTN1/2 is not fully understood. In this study, CSE combined with LPS was used to establish inflammation models in vitro and in vivo. Our study found that the expression of OCTN1/2 was downregulated in rat lung in vivo and in a human alveolar cell line in vitro after treatment with CSE and LPS compared with the control group, while the expression of inflammatory factors was upregulated. After treatment with ipratropium bromide (IB) or dexamethasone (DEX), the expression of OCTN1/2 was upregulated compared with that in the CSE-LPS model group, while the expression of inflammatory factors was significantly downregulated. After administration of the NF-κB inhibitor PDTC on the basis of the inflammatory status, the expression of OCTN1/2 was upregulated in the treated group compared with the CSE-LPS model group, while the expression of phospho-p65, phospho-IκBα and inflammatory factors was significantly downregulated. We further added the NF-κB agonist HSP70 and found a result that the exact opposite of that observed with PDTC. Our findings show that CSE combined with LPS can downregulate the expression of OCTN1/2 under inflammatory conditions, and that the downregulation of OCTN1/2 expression may partially occur via the NF-κB signaling pathway.

[Role of nitric oxide in pathogenesis of cold nerve injury].

OBJECTIVE: To study the role of nitric oxide (NO) in the pathogenesis of cold nerve injury and to explore its mechanism. METHODS: Cold nerve injury model was established in rat's sciatic nerve. Consistent and intermittent cooling of 4 degrees C for 2 hours were respectively applied to the sciatic nerves. Nerve samples were taken at different time points: immediately post-cooling and 4 h, 1 d & 3 d post-cooling. The group of aminoguanidine (AG) intervention was also established. Then NO levels in the nerves and blood serum were detected. Induced nitric oxide synthase (iNOS) in ganglion was determined by immunohistochemistry. Morphology of cooled sciatic nerves in the AG groups (consistent & intermittent cooling AG groups) and control groups (1 d time point of consistent & intermittent cooling groups) was observed by light microscope and electron microscope. RESULTS: At the time points of immediacy, 4 h, 3 d in the consistent cooling groups and the time points of immediacy, 4 h, 1 d in the intermittent cooling groups, different incremental degrees of NO levels in the cooled nerves (0.146 +/- 0.047), (0.216 +/- 0.048), (0.137 +/- 0.035), (0.154 +/- 0.027), (0.260 +/- 0.027), (0.218 +/- 0.042) micromol/g as compared with those of controls (0.098 +/- 0.022), (0.158 +/- 0.030), (0.085 +/- 0.020), (0.127 +/- 0.016), (0.72 +/- 0.027), (0.174 +/- 0.026) micromol/g, P < 0.01, P < 0.05). And NO levels in the cooled nerves at the time points of 4 h, 1 d, 3 d in the intermittent cooling groups were higher than those in the consistent cooling groups (P < 0.01, P < 0.05). NO levels in blood serum at the time points of immediacy and 1 d in the intermittent cooling groups (4.98 +/- 1.33) micromol/L, (4.02 +/- 0.68) micromol/L were higher than those in the consistent cooling groups (2.47 +/- 0.36) micromol/L, (3.00 +/- 0.67) micromol/L, P < 0.01). Both in consistent cooling and intermittent cooling groups, different incremental degrees of areas and integrated optical density (IOD) of iNOS positive staining in ganglions were found in cooled side as compared with the control side at different time points (P < 0.01, P < 0.05, P > 0.05), while those at the time point of immediacy in the intermittent cooling groups (131 686 +/- 24 549) , (4.1 +/- 0.13) x 10(9) were higher than those in the consistent cooling groups (78 558 +/- 34 849), (2.1 +/- 0.93) x 10(9), P < 0.05. NO level of cooled nerves in the intermittent cooling AG group (0.178 +/- 0.030) micromol/g was lower than those at the time point of 1 d in intermittent cooling groups (0.218 +/- 0.042) micromol/g, P < 0.05). Also a reduction of NO levels of blood serum, areas and IOD of iNOS positive staining was found in the AG groups as compared with the control groups (P < 0.05) while the reduction was more significantly found in the intermittent cooling AG group (P < 0.01, P < 0.05). Through light microscope and electron microscope, more severe pathological injury of cooled nerve was seen in the intermittent cooling group as compared with 1d time point of the consistent cooling groups, and a marked reduction of pathological injury was found when AG was administered. It was also more significant in the intermittent cooling AG group. CONCLUSION: NO plays a causative role in the pathogenesis of cold nerve injury, especially in intermittent cold nerve injury. The expression of iNOS is the main source of NO. Production of free radicals and the resulting toxic injury may be its main mechanism.

Comparative pharmacokinetics of baicalin after oral administration of pure baicalin, Radix scutellariae extract and Huang-Lian-Jie-Du-Tang to rats.

Huang-Lian-Jie-Du-Tang (HLJDT) is an important "heat-clearing" multiherb remedy of traditional Chinese medicine, and Radix scutellariae (Scutellaria baicalensis Georgi, Labiatae) is a key ingredient herb in it. Baicalin and wogonoside are two main effective ingredients enriched in Radix scutellariae. In the present study, pharmacokinetic differences of baicalin following oral administration of pure baicalin, Radix scutellariae extract, baicalin co-administrated with extract of the other three herbs of HLJDT and HLJDT were investigated in male S.D. rats with approximately the same dose of 200 mg/kg baicalin. The pharmacokinetic comparison of wogonoside was conducted only in Radix scutellariae extract and HLJDT. Plasma concentrations of baicalin and wogonoside were determined using HPLC method. Unpaired Student's t-test was used for statistical comparison. The results indicated that baicalin and wogonoside demonstrated bimodal phenomenon in the plasma profile. Some ingredients in the other three herbs of HLJDT, not in Radix scutellariae itself, had pharmacokinetic interaction with baicalin and wogonoside and hence decreased their systematic exposure level (p<0.01). The absorption site of baicalin was preliminary evaluated in rat using in situ absorption in stomach and different intestinal segments and results revealed the existence of double-site absorption of baicalin. The first absorption site was in upper intestinal, probably via directly absorption of baicalin; while the second absorption site was in colon in the form of aglygon.

MiR-146a rs2910164 polymorphism and head and neck carcinoma risk: a meta-analysis based on 10 case-control studies.

Two recent meta-analyses have been conducted on the relationship between miR-146a polymorphism (rs2910164) and head and neck cancer (HNC) risk. However, they have yielded conflicting results. Hence, the aim of the present study was to conduct a quantitative updated meta-analysis addressing this subject. Eligible studies up to Sep 2016 were retrieved and screened from the bio-databases and then essential data were extracted for data analysis. Next, subgroup analyses on ethnicity, source of controls, sample size, and genotyping method were also carried out. As a result, a total of 9 publications involving 10 independent case-control studies were included. The overall data indicated a significant association between miR-146a rs2910164 polymorphism and HNC risk [C vs. G: odds ratio (OR) = 1.14; 95% confidence interval (CI) = 1.00-1.31; CC+CG vs. GG: OR=1.21; 95%CI=1.02-1.43]. Variant alleles of miR-146a rs2910164 may have a correlation with increased HNC risk. Future well-designed studies containing large sample sizes are needed to verify this result.

Simultaneous determination of berberine and palmatine in rat plasma by HPLC-ESI-MS after oral administration of traditional Chinese medicinal preparation Huang-Lian-Jie-Du decoction and the pharmacokinetic application of the method.

A sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method has been developed and validated for the identification and quantification of berberine and palmatine in rat plasma. After the addition of the internal standard (IS) and alkalization with 0.5M sodium hydroxide solution, plasma samples were extracted by ethyl ether and separated by HPLC on a Shim-pack ODS (4.6 microm, 150 mm x 2.0mm i.d.) column using a mobile phase composed of A (0.08% formic acid and 2 mmol/l ammonium acetate) and B (acetonitrile) with linear gradient elution. Analysis was performed on a Shimadzu LC/MS-2,010A in selected ion monitoring (SIM) mode with a positive electrospray ionization (ESI) interface. [M](+)=336 for berberine; 352 for palmatine and [M+H](+)=340 for IS were selected as detecting ions, respectively. The method was validated over the concentration range of 0.31-20 ng/ml for berberine and palmatine. Inter- and intra-CV precision (R.S.D.%) were all within 15% and accuracy (%bias) ranged from -5 to 5%. The lower limits of quantification were 0.31 ng/ml for both analytes. The extraction recovery was on average 68.6% for berberine, 64.2% for palmatine. The validated method was used to study the pharmacokinetic profile of berberine and palmatine in rat plasma after oral administration of Huang-Lian-Jie-Du decoction.

Switchable thulium-doped fiber laser from polarization rotation vector to scalar soliton.

We experimentally demonstrate switchable temporal soliton generation from a thulium-doped fiber laser (TDFL), using carbon nanotubes as the mode-locker. With the help of residual polarization dependent loss of a wavelength division multiplexer, a weak nonlinear polarization rotation (NPR) effect can be achieved within the laser cavity, which may provide joint contribution for passive mode-locking operation. By finely adjusting the polarization to alter the strength of NPR-based saturable absorption, the TDFL either approaches the operation regime of scalar soliton with strong NPR effect, or generates polarization rotation locked vector soliton (PRLVS) with weak NPR effect. The scalar solitons and PRLVSs possess 3-dB optical spectrum bandwidth of 2.2 nm and 2 nm, pulse-width of 1.8 ps and 2 ps, respectively. Moreover, the PRLVSs demonstrate a typical energy exchange between two polarized components on optical spectra and a period-doubling feature in time domain. Such operation principle can also be used in 1550 nm band fiber lasers and other nonlinear systems.

Does CYP2E1 RsaI/PstI polymorphism confer head and neck carcinoma susceptibility?: A meta-analysis based on 43 studies.

BACKGROUND: Previous reports showed that CYP2E1 RsaI/PstI polymorphism may be a risk factor for cancers. Published meta-analyses in 2010 and 2011, respectively, on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to head and neck carcinoma (HNC) have generated inconsistent results. Thus, this study aimed to conduct an updated meta-analysis involving published studies up to Nov 2015 to get a more confidential result. METHODS: Eligible studies up to Nov 2015 were retrieved and screened. Data were extracted and a quantitative meta-analysis was conducted. Subgroup analyses on ethnicity, source of controls, sample size, genotyping method, smoking status, and drinking status were also performed. RESULTS: Forty-one publications including a total of 43 case-control studies were selected for analysis. The overall data under a homozygote comparison model indicated a significant association of CYP2E1 RsaI/PstI polymorphisms with HNC risk (c2c2 vs c1c1: odds ratio [OR] = 1.97; 95% confidence interval [CI] = 1.53-2.53). Similar results were observed in the Asian subgroup (c2c2 vs c1c1: OR = 1.98; 95%CI = 1.51-2.60; c2 vs c1: OR = 1.20; 95%CI = 1.03-1.39) and mixed population (c2 vs c1: OR = 1.41; 95%CI = 1.06-1.86) when the data were stratified by ethnicities. Interestingly, increased cancer risk only was shown among never-smokers (c2c2+c1c2 vs c1c1: OR = 1.44; 95%CI = 1.05-1.98) but not ever-smokers. CONCLUSION: CYP2E1 RsaI/PstI polymorphisms may modify the susceptibility to HNC, particularly among Asians, mixed population, and never-smokers. Future large and well-designed studies are needed to verify this conclusion.

MTHFR C677T polymorphism interaction with heavy alcohol consumption increases head and neck carcinoma risk.

MTHFR C677T polymorphism has been indicated to be a risk factor for cancers, but its association with head and neck cancer (HNC) risk remains inconclusive. In the present study, we aimed to get a more precise estimation by performing a quantitative meta-analysis. Published papers up to Jun 2014 was searched and screened. Necessary information was rigorously extracted for data pooling and analyzing, and then, subgroup analyses on ethnicity, source of controls, sample size, tumor type, smoking and drinking status were also carried out. As a result, twenty-three case-control studies including 14298 subjects were included. The overall data failed to reveal a significant association between MTHFR C677T polymorphism and HNC risk (homozygote comparison model: OR = 1.16; 95%CI = 0.93-1.45; dominant model: OR = 1.05; 95%CI = .90-1.21; recessive model: OR = 1.14; 95%CI = 0.93-1.38). However, in the subgroup analysis about drinking status, increase risk was shown in the heavy drinking subgroup (TT vs CC: OR = 3.11; 95%CI = 1.52-3.02). In conclusion, the results of the present study suggest that Homozygous TT alleles of MTHFR C677T polymorphism might be a risk factor for HNC among individuals who have a heavy drinking history. Further studies are needed to get a more definitive conclusion.