Docosahexaenoic Acid Reverses Epithelial-Mesenchymal Transition and Drug Resistance by Impairing the PI3K/AKT/ Nrf2/GPX4 Signalling Pathway in Docetaxel-Resistant PC3 Prostate Cancer Cells.

Drug resistance is a serious problem in cancer therapy. Growing evidence has shown that docosahexaenoic acid has anti-inflammatory and chemopreventive abilities. Studies have shown that autophagy inhibition and ferroptosis are promising therapeutic strategies for overcoming multidrug resistance. This study was aimed to examine whether docosahexaenoic acid (DHA) could reverse docetaxel resistance in prostate cancer cells. Cell survival was examined by MTT and colony formation. Protein expression was determined by Western blot. Reactive oxygen species (ROS) production was measured by flow cytometry. DHA displayed anti-cancer effects on proliferation, colony formation, migration, apoptosis, autophagy and epithelial mesenchymal transition. Glutathione-S-transferase π is an enzyme that plays an important role in drug resistance. DHA inhibited GSTπ protein expression and induced cytoprotective autophagy by regulating the PI3K/AKT signalling pathway in PC3R cells. DHA combined with PI3K inhibitor (LY294002) enhanced apoptosis by alleviating the expression of LC3B, (pro-) caspase- 3 and (uncleaved) PARP. DHA induced ferroptosis by attenuating the expression of glutathione peroxidase 4 (GPX4) and nuclear erythroid 2-related factor 2 (Nrf2). DHA-treated PC3R cells produced ROS. The ROS and cytotoxicity were reversed by treatment with ferrostatin-1. DHA combined with docetaxel inhibited EMT by regulating the expression of E-cadhein and N-cadherin. In summary, DHA reversed drug resistance and induced cytoprotective autophagy and ferroptosis by regulating the PI3K/AKT/Nrf2/GPX4 signalling pathway in PC3R cells. We propose that DHA could be developed as a chemosensitizer and that the PI3K/AKT /Nrf2/GPX4 signalling pathway might be a promising therapeutic target for overcoming cancer drug resistance.

[Effects of glutathione on oxidative stress, leptin and adiponectin in patients with obstructive sleep apnea complicated with metabolic syndrome].

Objective:The aim of this study is to analyze the effects of glutathione on oxidative stress, leptin and adiponectin in patients with obstructive sleep apnea（OSA） complicated with metabolic syndrome. Method:One hundred and fifty-nine patients with OSA and MS were enrolled in the group A according to the exclusion criteria. One hundred and fifty-nine patients with MS group were not included in the OSA group, and 159 patients were included in the control group. Before and after treatment, the levels of serum malondialdehyde （MDA）, superoxide dismutase （SOD）, Leptin and ADP were respectively detected, and the clinical effects of the three groups were compared. Result:Compared with the control group, the contents of MDA and Leptin in the case A and B groups were significantly higher than that of the control group, and the contents of SOD and ADP were significantly lower than that of the control group, and the difference was statistically significant, especially in case group A. The level of SOD and ADP was significantly higher in the group after treatment than before treatment, and the level of MDA and Leptin was significantly lower than before treatment. The difference was statistically significant, especially in case group A, too. Conclusion:Patients with OSA and MS are associated with oxidative stress. Glutathione can effectively improve the body's ability to resist oxidative stress, reduce oxidative damage, reduce leptin, and increase ADP levels.

[Proteomic analysis and verification of protein expression after upregulation of human CD99 in Hodgkin lymphoma cell line L428].

Objective: To investigate the proteins expression difference after upregulation of human CD99 in Hodgkin Lymphoma cell line, L428 cell, and verify the function of differential proteins. Methods: The differential proteins were detected by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry analysis, cluster analysis was done by GOfact. Results: There were 38 proteins screened out, of which 21 proteins were positively associated with CD99, while 17 proteins were negative. Among the 38 proteins, 32 proteins participated in biological process, and 35 proteins were involved in the composition and construction. And 28 proteins participated in multifaceted biological activities including antioxidation, protein binding, catalytic activity, regulation of enzyme, signal transduction, molecular structure, regulation of translation and ion transport. Conclusions: The changes of the differential proteins, correlated with cytoskeleton, cell differentiation, signal pathway and regulating gene expression, are closely relevant to the translation between Hodgkin/Reed-Sternberg and B lymphocyte cell.

[Effects of butylphthalide on plasma nitric oxide and endothelin-1 in severe elderly OSAHS patients].

Objective:To investigate the effect of butylphthalide on plasma nitric oxide(NO) and endothelin-1(ET-1) in severe elderly OSAHS patients. Method:A total of 120 severe elderly OSAHS patients were chosen by PSG measurement. According to random number table method, OSAHS patients were randomly divided into non-invasive ventilation control group(n=40), butylphthalide treatment group(n=40) and butylphthalide combined with non-invasive ventilation group (n=40). Non-invasive ventilation control group was given double level airway positive pressure ventilation treatment for six months, butylphthalide treatment group accepted oral butylphthalide therapy for six months, butylphthalide combined with non-invasive ventilation group was given double level airway positive pressure ventilation treatment and accepted oral butylphthalide therapy for six months. The changes of plasma NO and ET-1 were detected by immunoenzyme adsorption before treatment and three and six months after treatment. Result:The difference of plasma NO and ET-1 before treatment in the three groups was not statistically significant (P>0.05). Compared with before treatment, the level of plasma NO decreased and the level of plasma ET-1 increased in the three groups after three and six months treatment (P<0.01). Compared with butylphthalide treatment group, the level of plasma NO increased and the level of plasma ET-1 decreased after 3 and 6 months of treatment in both non-invasive ventilation control group and butylphthalide combined with non-invasive ventilation group (P<0.05). Compared with non-invasive ventilation control group, the level of plasma NO increased and the level of plasma ET-1 decreased after 3 and 6 months of treatment in butylphthalide combined with non-invasive ventilation group (P<0.05). Conclusion:Butylphthalide may improve the vascular endothelial function of severe elderly OSAHS patients by increasing the level of NO and decreasing the level of ET-1 in plasma.

[Effect of butylphthalide on oxidative stress and cognitive function in old obstructive sleep apnea hypopnea syndrome patients].

Objective:To explore the effect of butylphthalide on oxidative stress and cognitive function in old obstructive sleep apnea hypopnea syndrome (OSAHS)patients.Method:A total of 90 old OSAHS patients with cognitive impairment were choosed with Polysomnography（PSG）. By random number table method OSAHS patients were randomly divided into non-invasive ventilator group (n=30), butylphthalide with non-invasive ventilator group(n=30) and treatment group of butylphthalide(n=30). Non-invasive ventilator group was given continuous positive airway pressure treatment for three months, butylphthalide with non-invasive ventilator group accepted oral butylphthalide therapy and continuous positive airway pressure treatment for three months, treatment group of butylphthalide only accepted oral butylphthalide therapy for three months. Cognitive function of three groups wered observed by the Montreal cognitive assessment scale (MoCA) before and after treatment, at the same time, the changes of serum superoxide dismutase(SOD) and malondialdehyde(MDA) were detected by immunoenzyme-linked adsorption.Result:The differences of serum SOD and MDA before treatment among the three groups were not statistically significant (P＞0.05). Compared with before treatment, the level of serum SOD increased and the level of MDA decreased in the three groups (P<0.05). Compared with non-invasive ventilator group after treatment，the level of SOD increased and the level of MDA decreased in butylphthalide with non-invasive ventilator group (P<0.05)， the level of SOD decreased and the level of MDA increased in treatment group of butylphthalide (P<0.05). Compared with treatment group of butylphthalide after treatment, the level of SOD increased and the level of MDA decreased in butylphthalide with non-invasive ventilator group (P<0.05); The scores of MoCA on cognitive function before treatment in the three groups was not statistically significant (P＞0.05). After treatment the scores of MoCA on cognitive function in the three groups were higher than those before treatment (P<0.05). Compared with non-invasive ventilator group after treatment， the scores of MoCA increased in butylphthalide with non-invasive ventilator group (P<0.05),the the scores of MoCA decreased in treatment group of butylphthalide (P<0.05). Compared with treatment group of butylphthalide after treatment, the scores of MoCA increased in butylphthalide with non-invasive ventilator group (P<0.05).Conclution: Butylphthalide can improve the activity of antioxidant enzymes in the serum of old patients with OSAHS, inhibit the oxygen free radical and lipid peroxidation and to a certain extent improve the cognitive function.

Does body mass index truly affect mortality and cardiovascular outcomes in patients after coronary revascularization with percutaneous coronary intervention or coronary artery bypass graft? A systematic review and network meta-analysis.

BACKGROUND: Obesity, a comorbid medical condition, is usually observed in patients with established coronary artery disease. Paradoxically, patients with a higher body mass index (BMI) usually have better clinical outcomes after coronary revascularization. METHODS: We searched five online databases through December 2017. We identified studies reporting the rate of all-cause mortality or cardiovascular-related outcomes among patients after coronary revascularization with percutaneous coronary intervention or coronary artery bypass graft based on various BMI categories. Network meta-analysis was performed using Bayesian methods. RESULTS: Sixty-five records involving 865,774 participants were included in our study. A U-shaped association was observed across BMI categories for all-cause mortality. Using normal weight as the reference, all-cause mortality was increased for (relative risk [RR]: 2.4; 95% credibility interval [CrI]: 2.1-2.7) patients with underweight, whereas it was lowered in patients with overweight, obese, and severely obese. This association remained significant in many subgroups. We also observed that the risk of major adverse cardiovascular events (MACE) was lowest among patients with overweight. Furthermore, patients with underweight were associated with greater risks of myocardial infarction (RR: 1.9; 95% CrI: 1.4-2.5), cardiovascular-related mortality (RR: 2.8; 95% CrI: 1.6-4.7), stroke (RR: 2.0; 95% CrI: 1.3-3.3) and heart failure (RR: 1.7; 95% CrI: 1.1-2.7) compared with normal weight patients; no significant association was observed among individuals with higher BMI. CONCLUSIONS: The 'obesity paradox' does exist in patients after coronary revascularization, especially for patients with post-percutaneous coronary intervention. All-cause mortality in patients with high BMI is significantly lower compared with patients with normal weight. Furthermore, patients with underweight experience higher rates of cardiovascular outcomes compared with patients with normal weight.

[Pleural amoebic empyema: a case report].

In this paper, a case of pleural amoebic empyema and its diagnosis and treatment were reported.

[The effect of monrustet on the exhalation of nitric oxide and inflammatory cytokines in patients with asthma combined with OSAHS].

Objective:To study the effect of monrustet on fractional exhaled nitric oxide and inflammatory cytokines in the elderly with bronchial asthma combined obstructive sleep apnea hypopnea syndrome.Method:150 cases diagnosed as asthma were enrolled in this study. The patients were divided into bronchial asthma combined with OSAHS (n=72)and bronchial asthma (n=78). According to the different treatment methods , patients were divided into observation group and control group. Two groups were given common treatment with inhaled corticosteroids, and the observation group was taken orally montrast 10mg/night additionally. The fractional exhaled nitric oxide was detected before and after treatment. Serum were collected for detection of tumor necrosis factor alpha (TNR-α), Creactive protein (CRP) and interleukin 6 (IL-6), according to the sleep monitoring results, the sleep apnea low ventilation index (AHI) was calculated, and the changes of FeNO level,CRP,TNR-α,IL-6 and AHI were analyzed in the two groups.Result:Before treatment, the gender, age, degree of disease, FeNO level,TNR-α, CRP,IL-6 and AHI differences were not statistically significant in the two groups (P>0.05).After treatment, both groups of FeNO, TNR-α,CRP,IL-6 and AHI decreased before treatment (P < 0.05).The observation group was lower than the control group, and the difference was statistically significant (FeNO level, AHIP< 0.01,TNR-α, CRP,IL-6 P< 0.05).Conclusion::Montelukast can reduce the FeNO level, the expression of TNR-α, CRP, and IL-6 of patients of bronchial asthma combined with OSAHS. Further improvement of the patient's condition, and provide reference value for the clinical medicine of patients with asthma.

[Effects of ketotifen on fractional exhaled nitric oxide in patients with combined allergic rhinitis and asthma syndrome].

Objective:To study effects of ketotifen on fractional exhaled nitric oxide in patients with combined allergic rhinitis and asthma syndrome.Method:One hundred and twelve patients with asthma were selected from department of respiration, Affiliated Hospital of North China University of science and technology from January 2016 to 2017 in March. Eighty-four patients with allergic rhinitis were selected as the subjects, Randomly divided into two groups,including observed group(n=42) and control group(n=42).The control group was treated with antitussive,expectorant and inhaled corticosteroids, while the observed group in the control group combined with ketotifen 1 mg 2/ day oral treatment,the changes of FeNO and IL-17 in the two groups were compared after one month treament.Result:Before treatment, two groups of patients in general IL-17 and fractional exhaled nitric oxide ware no significant difference(P> 0.05).After treatment, compared to the control group, the observed group was significantly more effective,the difference was statistically significant(P <0.05);fractional exhaled nitric oxide in treatment group were lower than those in control group, the difference was statistically significant(P<0.05,P< 0.01).And the observed group was lower than the control group, and the differences were statistically significant,t(P<0.05).Conclusion:Ketotifen significantly reduce the FeNO of allergic rhinitis and asthma syndrome, reduce airway inflammation.

Combating against methicillin-resistant Staphylococcus aureus - two fatty acids from Purslane (Portulaca oleracea†L.) exhibit synergistic effects with erythromycin.

OBJECTIVES: The aims of this study were to identify the active ingredients from Portulaca oleracea L. (PO) that could provide synergism with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) and their possible mechanisms of resistance inhibition. METHODS: High-speed counter-current chromatography (HSCCC) coupled with gas chromatography-mass spectrometry and a panel of laboratory MRSA strains were used for checkerboard and efflux inhibitory assays. KEY FINDINGS: Linoleic and oleic acids were identified from HSCCC fraction 18 of PO with synergistic antibacterial activity when combined with erythromycin against RN4220/pUL5054. Ethidium bromide efflux inhibitory studies revealed that linoleic and oleic acids may interfere the activity of MsrA pump. By comparing among a panel of linoleic and oleic acids analogues, unsaturated fatty acids in salt form with cis configuration and an increase in number of double bonds were found to further increase the antibacterial activity when used alone or in combination with antibiotics. CONCLUSION: This study reported for the first time that two active ingredients, namely linoleic and oleic acids, were identified from PO with synergistic antibacterial activity when combined with erythromycin against MRSA RN4220/pUL5054 and possibly act by inhibiting the efflux pumps of the bacteria cells.

Spatial analysis for spring bloom and nutrient limitation in Xiangxi bay of three Gorges Reservoir.

The spatial and temporal dynamics of physical variables, inorganic nutrients and phytoplankton chlorophyll a were investigated in Xiangxi Bay from 23 Feb. to 28 Apr. every six days, including one daily sampling site and one bidaily sampling site. The concentrations of nutrient variables showed ranges of 0.02-3.20 mg/L for dissolved silicate (Si); 0.06-2.40 mg/L for DIN (NH(4)N + NO(2)N + NO(3)N); 0.03-0.56 mg/L for PO(4)P and 0.22-193.37 microg/L for chlorophyll a, respectively. The concentration of chlorophyll a and inorganic nutrients were interpolated using GIS techniques. The results indicated that the spring bloom was occurred twice in space during the whole monitoring period (The first one: 26 Feb.-23 Mar.; the second one: 23 Mar.-28 Apr.). The concentration of DIN was always high in the mouth of Xiangxi Bay, and PO(4)P was high in the upstream of Xiangxi Bay during the whole bloom period. Si seems no obvious difference in space in the beginning of the spring bloom, but showed high heterogeneity in space and time with the development of spring bloom. By comparing the interpolated maps of chlorophyll a and inorganic variables, obvious consumptions of Si and DIN were found when the bloom status was serious. However, no obvious depletion of PO(4)P was found. Spatial regression analysis could explained most variation of Chl-a except at the begin of the first and second bloom. The result indicated that Si was the factor limiting Chl-a in space before achieved the max area of hypertrophic in the first and second bloom period. When Si was obviously exhausted, DIN became the factor limiting the Chl-a in space. Daily and bidaily monitoring of Site A and B, representing for high DIN: PO(4)P ratio and low DIN:PO(4)P ratio, indicated that the concentration of Si was decreased with times at both site A and B, and the dramatically drop of DIN was found in the end monitoring at site B. Multiple stepwise regression analysis indicated that Si was the most important factor affect the development of spring bloom both at site A and B in time series.

Chiral separation of glycidyl selenide and glycidyl sulfide racemates on cellulose-based chiral stationary phases.

In recent years, a growing interest has been paid to glycidyl selenide and glycidyl sulfide racemic compounds for their importance in the life science field. In this study, cellulose-based chiral stationary phases are employed for the separation of glycerin selenium and glycerin sulfur racemates. Most analytes obtain satisfactory separation. In order to optimize the resolution of racemates, mixtures of n-hexane with different alcohols are used as mobile phases. The structural features of these racemic compounds affecting chiral discrimination are discussed in detail. The results in this study suggest that the chiral recognition mechanism for these racemic compounds involve two factors: (a) the substitution residue on a nonchiral atom can play a direct or indirect effect during chiral discrimination and (b) the competition between hydrogen-bonding and pi-pi interaction exists for compounds containing both the hydroxyl and aromatic group at the same time. The two interactions play an opposite role in the chiral discrimination process.

[Direct optical resolution of the enantiomers of biphenyl compounds by high performance liquid chromatography on amylose tris-(3,5-dimethylphenylcarbamate) stationary phase].

A chiral stationary phase(CSP) was prepared by coating amylose tris-(3,5-dimethylphenylcarbamate) onto aminopropylated spherical silica gel. The enantioselective chromatographic separation of a series of biphenyl compounds with antihepatitis activity was performed for the first time on CSP. The effect of alcohol modifiers in mobile phase was investigated. The mobile phases used in the study were hexane modified by ethanol, 1-propanol, 1-butanol or 2-propanol. It was found that the retention times and the separation of the enantiomers of biphenyl compounds on the CSP were dramatically influenced by the nature of alcohols in the mobile phase, and the best alcohol modifier for some compounds was ethanol. The interaction between the stationary phase and samples was also discussed.

Stability of protease Q against autolysis and in sodium dodecyl sulfate and urea solutions.

Protease Q, a recently discovered subtilisin-like protease, exhibited unusual stability in 10% sodium dodecyl sulfate (SDS) and 8 M urea solutions. In 2% SDS it exhibited higher activity than the control, and in 10% SDS it retained 50% of its original activity when azocoll was used as substrate. Kinetic studies showed that the decrease in the activity of protease Q in SDS solutions followed a first order kinetics with a half-life of 446, 278, 78, and 24 h in 1%, 2%, 5%, and 10% SDS, respectively, at 25 degrees C. Protease Q was also stable against autolysis. In 20 mM Tris-HCl buffer (pH 8.3) containing 1.0 mM CaCl2, protease Q had a half life of 2822 h and 725 h at room temperature and at 37 degrees C, respectively. The enzyme was able to completely hydrolyze beta-lactoglobulin, beta-casein, and keratin in 8-10 M urea.

Encapsulation of food ingredients.

Microencapsulation is a relatively new technology that is used for protection, stabilization, and slow release of food ingredients. The encapsulating or wall materials used generally consist of starch, starch derivatives, proteins, gums, lipids, or any combination of them. Methods of encapsulation of food ingredients include spray-drying, freeze-drying, fluidized bed-coating, extrusion, cocrystallization, molecular inclusion, and coacervation. This paper reviews techniques for preparation of microencapsulated food ingredients and choices of coating material. Characterization of microcapsules, mechanisms of controlled release, and efficiency of protection/stabilization of encapsulated food ingredients are also presented.

Mechanisms of action of beta-adrenergic agents on the arrhythmogenic transient inward current in rabbit Purkinje fibers.

Catecholamines increase the amplitudes of oscillatory afterpotentials (OAP) and peak magnitude of the transient inward current (Iti) responsible for OAP. The objectives of this study were to determine whether beta-adrenoceptor stimulation can induce Iti, and to determine the mechanism by which beta-adrenoceptor stimulation increases the magnitude of Iti. Experiments were performed using standard two electrode voltage--clamp techniques in isolated rabbit Purkinje fibers. Holding potential was either -50 or -80 mV. The Iti was elicited by repolarizing steps, following 1.5 or 3 s activating steps to potentials near 0 mV. Isoproterenol (ISO) failed to induce the Iti at concentrations from 10(-8) to 10(-6)M. However ISO (10(-7)M) significantly increased peak magnitude of spontaneously occurring Iti (P less than 0.05), or Iti induced by acetylstrophanthidin (AS) (P less than 0.05). ISO also shifted the minimum activation voltage 10 mV more negative (P less than 0.05). The current-voltage relationship demonstrated that ISO significantly increased the range of potentials over which Iti greater than or equal to 5 nA occurred, but did not significantly shift the voltage at which maximum peak current was observed. Effects of ISO on Iti were blocked by 10(-7)M propranolol or atenolol. Mn2+ (2 mM) or verapamil (2 microM) blocked the slow inward current (Isi) more than 80% before substantially decreasing peak Iti. Either agent blocked stimulation of Isi but not Iti by ISO at 10(-7)M. In contrast, quinacrine (20 microM), an inhibitor of Na(+)-Ca2+ exchange, abolished stimulation of Iti by ISO while having no significant effect on Isi. Our results indicate that beta-adrenoceptor stimulation cannot induce Iti in rabbit Purkinje fibers, but can enhance the Iti induced by other means, by stimulating Na(+)-Ca2+ exchange.

A sensitive method for simultaneous determination of histamine and noradrenaline with high-performance liquid chromatography/electrochemistry.

A simple and reliable high-performance liquid chromatographic method is described for the simultaneous determination of histamine (His), which cannot be directly oxidized, and noradrenaline (NA), which can be directly oxidized within the useful working potential range. The isoindole products formed by precolumn derivatization of His and NA with o-phthalaldehyde (OPA) and 2-mercaptoethanol (2-ME) yielded a linear relationship of detection between the electrochemical signal and the compound content to a minimum detectable limit of 50 pg (signal-to-noise ratio = 3:1) for both compounds at 0.5 nA of detector range. Without 2-ME, OPA derivatives of both His and NA were not detectable electrochemically at the oxidation potential range from 0 to + 1 V. Although the peak potential was +0.85 V for both His and NA, we used +0.7 V for both compounds to keep background noise minimal. The capacity factors of some electrochemically interfering compounds were also determined. The significance of OPA/2-ME derivative of NA is discussed relative to the direct oxidation of catecholamines. An example of a practical application of the method to the determination of His and NA in rat cardiac tissue is presented.

Effects of alpha-adrenergic agents on generation of oscillatory afterpotentials and triggered activity in rabbit Purkinje fibers.

Effects of alpha 1- and alpha 2-adrenergic agonists and antagonists on oscillatory afterpotentials (OAP) and triggered activity induced by acetylstrophanthidin (AS) or 8 mM Ca2+ (with 2 mM K+) were studied with standard microelectrode techniques in isolated rabbit heart Purkinje fibers. Experiments were conducted in the presence of 0.5 microM propranolol. Phenylephrine (PE, 0.5 to 10 microM) increased the amplitude of OAP and induced triggered activity when subthreshold OAP were caused by high Ca2+. In contrast, PE decreased the amplitude of OAP and suppressed triggered activity induced by acetylstrophanthidin. Prazosin at 0.5 microM did not affect the amplitudes of OAP by itself, but abolished both the inhibitory effect of PE on AS-induced OAP and the stimulatory effect of PE on high Ca2(+)-induced OAP. At 2 microM, prazosin alone reduced the amplitude of OAP and suppressed triggered activity induced by either acetylstrophanthidin or high Ca2+. While clonidine (0.5 to 10 microM) did not affect OAP or induction of triggered activity, yohimbine (2 microM) decreased the amplitude of OAP and abolished triggered activity induced by either acetylstrophanthidin or high Ca2+. Thus, specific alpha 1-adrenergic actions of phenylephrine may exert either pro-arrhythmic or antiarrhythmic effects on OAP and triggered activity depending on the method of induction of OAP. The alpha 1- and alpha 2-antagonists prazosin and yohimbine both exert direct antiarrhythmic effects in addition to their adrenergic blocking actions.