Neurochemical and brain functional changes in the ventromedial prefrontal cortex of first-episode psychosis patients: A combined functional magnetic resonance imaging-proton magnetic resonance spectroscopy study.

OBJECTIVE: Previous studies showed alterations of brain function in the ventromedial prefrontal cortex of schizophrenia patients. Also, neurochemical changes, especially GABA level alteration, have been found in the medial prefrontal cortex of schizophrenia patients. However, the relationship between GABA level in the ventromedial prefrontal cortex and brain functional activity in schizophrenia patients remains unexplored. METHODS: In total, 23 drug-naïve, first-episode psychosis patients and 26 matched healthy controls completed the study. The single voxel proton magnetic resonance spectroscopy data were acquired in ventromedial prefrontal cortex region, which was used as the seed region for resting-state functional connectivity analysis. The proton magnetic resonance spectroscopy data were processed to quantify the concentrations of GABA+, glutamine and glutamate, and N-acetylaspartate in ventromedial prefrontal cortex. Spearman correlation analysis was used to examine the relationship between metabolite concentration, functional connectivity and clinical variables. Pearson correlation analysis was used to examine the relationship between GABA+ concentration and functional connectivity value. RESULTS: In first-episode psychosis patients, GABA+ level in ventromedial prefrontal cortex was higher and was positively correlated with ventromedial prefrontal cortex-left middle orbital frontal cortex functional connectivity. N-acetylaspartate level was positively correlated with positive symptoms, and the functional connectivity between ventromedial prefrontal cortex and left precuneus was negatively associated with negative symptoms of first-episode psychosis patients. CONCLUSION: Our results indicated that ventromedial prefrontal cortex functional connectivity changes were positively correlated with higher local GABA+ level in first-episode psychosis patients. The altered neurochemical concentration and functional connectivity provide insights into the pathology of schizophrenia.

Exploring host-guest interactions of sulfobutylether-ß-cyclodextrin and phenolic acids by chemiluminescence and site-directed molecular docking.

We have developed a rapid method that allows us to characterize the binding interaction of sulfobutylether-ß-cyclodextrin (SBE-ß-CD) with five therapeutically important phenolic acids: ferulic acid, caffeic acid, gallic acid, protocatechuic acid, and vanillic acid. The method utilizes a flow-injection chemiluminescence (FI-CL) technique that relies on the inhibition of a cyclodextrin-luminol chemiluminescence (CL) by increasing amounts of the phenolic acids (PAs). This loss of CL with increasing amounts of PAs fits the equation lg[(I0-Is)/Is]=lgKPAs+nlg[PAs], allowing calculation of the binding constant (KPAs) and stoichiometric ratio (n). The five phenolic acids and SBE-ß-CD formed complexes with a stoichiometric ratio of 1:1. The binding constants were on the order of 10(7) M(-1). These results showed a good correlation with the scores calculated by molecular docking. Further investigation by site-directed molecular docking and linear correlation analysis revealed that PAs entered the larger cavity of SBE-ß-CD and the formation constants mainly depended on the number of hydrogen bond acceptors in the PAs structures. All these results indicate that the CL-based affinity method can be used for direct determination of host-guest inclusion interactions and has great potential to become a reliable alternative for quantitatively studying host-guest binding and drug-protein interactions.

Binding study of lysozyme with Al(III) using chemiluminescence analysis.

The binding behavior of lysozyme with Al(III) is described using luminol as a luminescence probe by flow injection-chemiluminescence (FI-CL) analysis. It was found that the CL intensity of the luminol-lysozyme reaction could be markedly enhanced by Al(III), and the increase in CL intensity was linear with the Al(III) concentration over the range 0.3-30.0 pg mL(-1) , with a detection limit of 0.1 pg mL(-1) (3σ). Based on the interaction model of lysozyme with Al(III), lg[(I - I0 )/(2I0 - I)] = lgK + nlg[M], the binding constant K = 6.84 × 10(6) L mol(-1) and the number of binding sites (n) = 0.76. The relative standard deviations were 3.2, 2.4 and 2.0% for 10.0, 20.0 and 30.0 pg mL(-1) Al(III) (n = 7), respectively. This new method was successfully applied to continuous, quantitative monitoring of picogram level Al(III) in human saliva following oral intake of compound aluminum hydroxide tablets. It was found that Al(III) in saliva reached a maximum of 101.2 ng mL(-1) at 3.0 h. The absorption rate constant ka , elimination rate constant k and half-life time t1/2 of Al(III) were 1.378 h(-1) , 0.264 h(-1) and 2.624 h, respectively.

Revealing interaction between sulfobutylether-ß-cyclodextrin and reserpine by chemiluminescence and site-directed molecular docking.

The host-guest interaction between sulfobutylether-ß-cyclodextrin (SBE-ß-CD) and reserpine (RSP) is described using flow injection-chemiluminescence (FI-CL) and site-directed molecular docking methods. It was found that RSP could inhibit the CL intensity produced by a luminol/SBE-ß-CD system. The decrease in CL intensity was logarithmic over an RSP concentration range of 0.03 to 700.0 nM, giving a regression equation of ∆I = 107.1lgCRES + 186.1 with a detection limit of 10 pM (3σ). The CL assay was successfully applied in the determination of RSP in injection, saliva and urine samples with recoveries in the range 93.5-106.1%. Using the proposed CL model, the binding constant (KCD-R ) and the stoichiometric ratio of SBE-ß-CD/RSP were calculated to be 7.4 × 10(6) M(-1) and 1 : 1, respectively. Using molecular docking, it was confirmed that luminol binds to the small cavity of SBE-ß-CD with a nonpolar interaction, while RSP targeted the larger cavity of SBE-ß-CD and formed a 1 : 1 complex with hydrogen bonds. The proposed new CL method has the potential to become a powerful tool for revealing the host-guest interaction between CDs and drugs, as well as monitoring drugs with high sensitivity.

Ultrasensitive determination of diphacinone by flow injection chemiluminescence: application to quantification in biofluids and photodegradation monitoring in water samples.

An ultrasensitive, quick, and simple approach for the determination of pg levels of diphacinone (DPN) by flow injection chemiluminescence (CL) analysis is proposed for the first time. It is based on the quenching effect of DPN on the CL intensity from a luminol-bovine serum albumin (BSA) CL system, for which the CL intensity decrease was linearly proportional to the logarithm of DPN concentration in the range of 5.0 to 5000 pg/mL. The LOD for DPN determination was as low as 2.0 pg/mL (3α a), and the RSD values were less than 5.0%. One determination cycle that included sampling and washing could be performed in 0.5 min with a sample throughput of 120/h under the optimum experimental conditions. This proposed method was successfully applied to determining DPN in human gastric juice and serum samples with recoveries from 91.8 to 114.3%, and to continuous monitoring of the degradation of DPN in water samples exposed to sunlight during 43 h with a variation ratio of 99.99%. The possible interaction behavior of BSA-DPN is briefly discussed.

RNA-Seq Analysis Reveals Potential Neuroprotective Mechanisms of Pachymic Acid Toward Iron-Induced Oxidative Stress and Cell Death.

Iron dysregulation is a crucial factor in the development of neurological diseases, leading to the accumulation of reactive oxygen species (ROS) and oxidative stress, triggering inflammatory responses, and ultimately causing neurological impairment. Pachymic acid (PA) is an active ingredient extracted from the medicinal fungus Poria cocos, which has been reported with multiple pharmacological effects, including anti-inflammatory, anti-ischemia/reperfusion, and anticancer actions. In this study, we test whether PA have neuroprotection effect aganist ferrous ions induced toxicity in SH-SY5Y cells. It was found that pre-treatment with PA reduced intracellular ROS levels, increased mitochondrial membrane potential, and protected cells from apoptotic death. RNA-seq and qRT-PCR results indicated that PA can regulate the key genes IL1B, CXCL8, CCL7, and LRP1 on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as NF-κB signaling pathway, IL-17 signaling pathway, to prevent Fe2+-induced apoptotic cell death. Our research indicated that PA has potential therapeutic effects on the neuroprotection by regulating neuroinflammation and oxidative stress damage.

Subnanogram determination of aniracetam in pharmaceutical preparations and biofluids by flow injection analysis with chemiluminescence detection based on its enhancement of the myoglobin-luminol reaction.

A novel flow injection chemiluminescence method with a myoglobin-luminol system is described for determining aniracetam. Myoglobin-bound aniracetam produced a complex that catalyzed the chemiluminescence reaction between luminol and myoglobin, leading to fast chemiluminescence. The chemiluminescence intensity in the presence of aniracetam was remarkably enhanced compared with that in the absence of aniracetam. Under the optimum reaction conditions the chemiluminescence increment produced was proportional to the concentration of aniracetam in the range of 0.1-1000.0 ng/mL (R2 = 0.9992), with a detection limit of 0.03 ng/mL (3delta). At a flow rate of 2.0 mL/min, the whole process, including sampling and washing, could be completed in 0.5 min, offering a sampling efficiency of 120/h; the RSD was less than 3.0% (n = 5). The method was satisfactory for determination of aniracetam in pharmaceutical preparations and human urine and serum samples. A possible mechanism of the reaction is also discussed.

A valuable way for understanding the relationships between lysozyme and cephalosporin analogues by flow injection chemiluminescence.

The photochemical reaction mechanism of lysozyme with cephalosporin analogues was investigated with luminol used as a luminescence probe by flow injection chemiluminescence. It was found that Glu35 and Asp52 of lysozyme accelerated the rate of excited 3-aminophthalate electrons transferring and enhanced the chemiluminescence signal of luminol, producing steady-state chemiluminescence in the flow injection system with relative standard deviations less than 3.0%. It was also found that cephalosporin analogues could enter into the site of Trp62 in lysozyme forming 1 : 1 complex which leads to a conformational change of lysozyme, giving the effect of chemiluminescence quenching from luminol-lysozyme. Based on the photochemical behavior of luminol/lysozyme and cephalosporin, a model of lysozyme-cephalosporin interaction, lg[(I(0)-I)/I]=lgK(D) + nlg[D], was established. Using the proposed model, the interaction parameters and the binding ability of lysozyme with cephalosporin were successfully obtained, and the results agreed very well with the results obtained by fluorescence.

Sensitive determination of gentiopicroside in medicine and bio-fluids using luminol-myoglobin chemiluminescence combined with flow injection technique.

A novel chemiluminescence method for the determination of gentiopicroside is presented, which was based on the inhibitory effect of gentiopicroside on the chemiluminescence reaction between luminol and myoglobin in a flow-injection system. The decrement of chemiluminescence intensity was linear with the logarithm of gentiopicroside concentration over the range from 10.0 pg mL(-1) to 500.0 ng mL(-1) (r(2) = 0.9992), with a detection limit of 3.0 pg mL(-1) (3σ). At a flow rate of 2.0 mL min(-1), a complete analytical process could be performed within 0.5 min, including sampling and washing, with a relative standard deviation of less than 3.0% (n = 5). The proposed procedure was applied successfully in the determination of gentiopicroside in pharmaceutical preparations, human urine and serum without any pretreatment procedure. The possible mechanism of the reaction was also discussed.

Determination of Sudan IV in hot chilli powder with luminol/dissolved oxygen chemiluminescence system.

BACKGROUND: A green, simple and sensitive flow injection chemiluminescence (CL) procedure is proposed for the determination of Sudan dyes. The method is based on the finding that Sudan I, II, III and IV markedly enhance the CL intensity of the luminol/dissolved oxygen reaction. RESULTS: The increment in CL intensity was proportional to the concentration of Sudan I, II, III and IV, giving calibration graphs linear over the ranges 0.007-1, 0.5-30, 1-10 and 0.7-300 ng mL(-1) respectively (R(2) >or= 0.9981), with limits of detection of 0.002, 0.2, 0.3 and 0.2 ng mL(-1) respectively. At a flow rate of 2 mL min(-1), complete determination of Sudan dyes, including sampling and washing, could be accomplished in 40 s, with relative standard deviations of less than 5% (n = 7). CONCLUSION: The proposed method was successfully applied to the determination of Sudan IV in contaminated hot chilli powder, with recoveries ranging from 89.3 to 108.4%. The possible mechanism of enhancement of the luminol/dissolved oxygen CL reaction by Sudan IV can be attributed to the acceleration of electron transfer. Compared with other procedures, the proposed CL method offers the highest sensitivity and the least reagent consumption for the determination of Sudan IV.

Study on the binding behavior of lysozyme with cephalosporin analogues by fluorescence spectroscopy.

It was first found that the intrinsic fluorescence of lysozyme at 340 nm can be quenched by cephalosporin analogues through the static quenching and non-radiative energy transferring procedure. In the acetate buffer solution with pH 7.0 and 298 K, the quenching fluorescence intensity was in a good linearity over the concentration of drugs in the range of 1-100 micromol L(-1), 0.1-100 micromol L(-1), 0.5-100 micromol L(-1) and 0.05-100 micromol L(-1) for cefradine, cefuroxime, cefotaxime and ceftriaxone, respectively. The quenching ability or the binding ability of the studied drugs followed the pattern: ceftriaxone > cefotaxime > cefuroxime > cefradine, which was close to the order of their antibacterial ability. The binding parameters including the association constant and the number of binding potential point were calculated at different temperatures (288, 298 and 308 K), and thermodynamic parameters DeltaH degrees, DeltaS degrees and DeltaG degrees were given. The binding mode of lysozyme with cephalosporins showed that the hydrophobic effect might play a major role. The binding distance between cephalosporin and tryptophan residue in lysozyme was obtained. The results provided the quantitative information for the binding of cephalosporin to lysozyme, and it was suggested that the drugs probably bound to the active site near Trp62 in lysozyme.

A study on photochemical behavior of lysozyme-bromophenol blue complex and its analytical application.

It was found that macromolecular complexes were formed between lysozyme and bromophenol blue (BPB) with the electrostatic attraction in acetate medium (pH 6.5). The binding constant and the number of binding site for lysozyme-BPB complex were obtained, and the thermodynamic parameters were given. In addition, a remarkable enhancement of resonance light scattering (RLS) intensity for the macromolecular complex was observed with a scattering peak at 336 nm. And the increment of RLS intensity was proportional to the concentration of lysozyme in the range of 5 ng ml(-1) to 10.0 microg ml(-1). The influence of experimental conditions including pH, BPB concentration, and ionic strength on RLS system were tested, especially the effect of temperature was examined in detail. The proposed method was successfully applied to determine lysozyme in human saliva and tear samples without any special pretreatment. Compared with other methods the proposed method is of higher sensitivity and wider linear range.

In vitro monitoring chlorogenic acid in human urine and serum by a flow injection system exploiting the luminol-dissolved oxygen chemiluminescence reaction.

A sensitive flow injection chemiluminescence method, based on the inhibitory effect of chlorogenic acid on the reaction between luminol and dissolved oxygen, was presented for the determination of chlorogenic acid. It was found that the decrease of chemiluminescence intensity was linear with the logarithm of chlorogenic acid concentration over the range from 1.0 ng.ml(-1) to 100 ng.ml(-1) (r(2) = 0.9978), with the detection limit of 0.3 ng.ml(-1) (3 sigma). At the flow rate of 2.0 ml.min(-1) for each line, a complete analytical process could be performed within 0.5 min, including sampling and washing, with a relative standard deviation lower than 3.0% (n = 5). The proposed procedure was applied successfully to determine chlorogenic acid in Flo Lonicerae for different drawn time and monitor the excretion of chlorogenic acid in human urine. It was found that the excretive amounts of chlorogenic acid in urine reached its maximum in 2 hours after intake of Flo Lonicerae tea, presenting an excretive ratio of 63.82% in 6 hours. With urinary excretion rate method, the total elimination rate constant k and half-life time t(1/2) of chlorogenic acid was calculated, which were 0.7667 and 0.91 hours, respectively.

A sensitive chemiluminescence procedure for the determination of carbon monoxide with myoglobin-luminol chemiluminescence system.

A novel chemiluminescence method combined with the flow injection technique for the determination of carbon monoxide is presented in this paper. The chemiluminescence signal based on the reaction between myoglobin and luminol in an alkaline medium was remarkably enhanced by carbon monoxide. The enhanced chemiluminescence intensity was linear with carbon monoxide concentration in the range from 0.01 to 10.0 pmol.L(-1), and the detection limit was 3x10(-3) pmol.L(-1) (3sigma). The whole process, including sampling and washing, could be completed in 0.5 min with a relative standard deviation of less than 4.0%. The proposed method was applied successfully in the assay of carbon monoxide in human serum and artificial water samples without any pretreatment procedure.

Flow injection chemiluminescence determination of sudan I in hot chilli sauce.

A chemiluminescence method based on the luminol-H2O2 system with flow injection technology was proposed for the determination of sudan I in hot chilli sauce. It was found that sudan I could enhance chemiluminescence intensity generated from the luminol-H2O2 system. The increment of chemiluminescence intensity was proportional to the concentration of sudan I, giving a calibration graph linear over the concentration from 10 pg mL-1 to 7 ng mL-1 (R 2 = 0.9980) with the detection limit of 3 pg mL-1 (3sigma) and the quantification limit of 7.5 pg mL-1. At a flow rate of 2.0 mL min-1, one analysis cycle, including sampling and washing, could be accomplished in 60 s with a relative standard deviation of <5.0%. The method has been applied successfully to the determination of sudan I in Pixian douban, Golden Mark guilin chilli sauce, and Golden Mark satay sauce, and the recovery was 90.6-110.0%.

In vitro monitoring picogram roxithromycin in human urine using flow injection chemiluminescence procedure.

A sensitive chemiluminescence method, based on the enhancive effect of roxithromycin on the chemiluminescence reaction between luminol and hydrogen peroxide in a flow injection system, was proposed for the determination of roxithromycin. The increment of chemiluminescence intensity was linear with roxithromycin concentration in the range 1.0-1000 pg ml(-1) with the detection limit of 0.3 pg ml(-1) (3sigma). At a flow rate of 2.0 ml min(-1), a complete analytical process could be performed within 0.5 min, including sampling and washing, with a relative standard deviation of less than 5%. The proposed procedure was applied successfully in the monitoring of roxithromycin in human urine without any pre-treatment procedures and it was found that roxithromycin in urine reached its maximum after orally administrated for two hours, presenting an excretive ratio of 4.6% in 12 h. With urinary excretion rate method, the total elimination rate constant k and half-life time t(1/2) of roxithomycin was calculated, which was 0.1831, 3.785 h.

Rapid determination of clindamycin in medicine with myoglobin-luminol chemiluminescence system.

A sensitive chemiluminescence method, based on the inhibitory effect of clindamycin on the chemiluminescence reaction between luminol and myoglobin in a flow-injection system, is proposed for the determination of clindamycin. The decrement of chemiluminescence intensity is linear with the logarithm of clindamycin concentration over the range from 0.1 to 70.0 ng ml-1 (r2=0.9995), with the detection limit of 0.03 ng ml-1 (3sigma). At a flow rate of 2.0 ml min-1, a complete analytical process could be performed within 0.5 min, including sampling and washing, with a relative standard deviation of less than 3.0% (n=5). The proposed procedure was applied successfully to the determination of clindamycin in capsules without any pretreatment process.

Pharmacokinetic of pseudoephedrine in rat serum with luminol-pepsin chemiluminescence system by flow injection analysis.

Pepsin (Pep) accelerated the electron transferring rate of excited 3-aminophathlate and enhanced luminol-dissolved oxygen chemiluminescence (CL) intensity, and the flow injection (FI) luminol-Pep CL system was first developed. It was found that the CL intensity of luminol-Pep reaction could be remarkably inhibited by pseudoephedrine (PE); the decrement of CL intensity was linear to the logarithm of PE concentration in the range of 0.1∼100.0 nmol L(-1) with a detection limit of 0.03 nmol mL(-1) (3σ). At a flow rate of 2.0 mL min(-1), the complete process including washing and sampling was performed within 40 s, offering a sample throughput of 90 h(-1). This proposed method was successfully applied to determining PE in rat serum for 18 h after intragastric administration with the elimination ratio of 42.34 % and recoveries from 90.3 to 110.6 %. The pharmacokinetic results showed that PE could be rapidly absorbed into serum with peak concentration (C max) of 1.45 ± 0.18 g L(-1) at the time (T max) of 1.49 ± 0.02 h; the absorption half-life (0.35 ± 0.04 h), elimination half-life (1.86 ± 0.24 h), the area under curve (109.81 ± 6.03 mg L(-1) h(-1)), mean residence time (3.82 ± 0.27 h), and elimination rate constant (2.26 ± 0.23 L g(-1) h(-1)) in rats vivo were derived, respectively. The possible CL mechanism of luminol-Pep-PE reaction was discussed by FI-CL, fluorescence, and molecular docking (MD) methods.

A new green analytical procedure for monitoring sub-nanogram amounts of chlorpyrifos on fruits using flow injection chemiluminescence with immobilized reagents.

A novel green method using flow injection chemiluminescence with controlled-reagent-release technology has been investigated for the rapid and sensitive monitoring of sub-nanogram amounts of chlorpyrifos. The analytical reagents involved in chemiluminescence (CL) reaction, luminol and periodate, were both immobilized on an anion-exchange column. The CL signals produced by the reaction between luminol and periodate, which were eluted from the column through water injection, were decreased in the presence of chlorpyrifos. The decrease of CL intensity was linear over the logarithm of concentration of chlorpyrifos ranging from 0.48 to 484.0 ng x mL(-1) (r(2) = 0.9969), and the limit of detection was 0.18 ng x mL(-1) (3sigma). At a flow rate of 2.0 mL x min(-1), the determination of chlorpyrifos, including sampling and washing, could be performed in 0.5 min with a relative standard deviation of less than <3.0%. The proposed method was applied successfully in an assay of remnant chlorpyrifos on fruits such as orange and shaddock with the recovery of 94.4-107.4%. The change of the concentration of chlorpyrifos in a water sample was also investigated, and the variation rate was 99.96% during 35 h in the open air.

Sensitive chemiluminescence assay for risperidone in pharmaceutical preparations.

A sensitive chemiluminescence (CL) method to determine the antipsychotic risperidone (RSP) is proposed, based on the catalytic effect of risperidone on the CL reaction between luminol and hydrogen peroxide in flow system. The increment of CL intensity was correlated with risperidone concentration in the range of 10pg ml(-1) to 1.0ng ml(-1) with a relative standard deviation of less than 5.0% (n = 5); and a limit of detection of 4pg ml(-1) (3sigma). At a flow rate of 2.0ml min(-1), the flow injection CL method exhibited both high sensitivity and excellent selectivity giving a throughput of 120 samples per hour. The proposed method was applied successfully to the determination of risperidone in pharmaceutical preparations.