Cp Activity Research Articles

Rational Assembly of Three-component Coordination Polymers as Heterogeneous Catalysts for CO2 Cycloaddition and Cyanosilylation Reactions.

Four new coordination polymers based on 5-(((1H-imidazol-2-yl)methyl)amino) isophthalic acid (H3L) and auxiliary ligands (1,10-phenanthroline, 2,2'-bipyridine, and 4,4'-bipyridine), namely, {[Zn(HL)(phen)(H2O)]·2H2O}n (CP 1), {[Ni(HL)(phen)(H2O)]}n (CP 2), {[Ni(HL)(2,2'-bpy)(H2O)]·2H2O}n (CP 3) and {[Cd(HL)(4,4'-bpy)0.5(H2O)]·2H2O}n (CP 4) were rationally assembled. Furthermore, these four CPs were screened as heterogeneous catalysts for CO2 cycloaddition and cyanosilylation reactions under mild conditions. The catalytic experiments showed that CP 1 had the better catalytic performance, excellent substrate tolerance and recyclability for the above two reactions. It is speculated that the excellent activity of CP 1 may be due to the open Lewis base site and the Lewis acidic characteristics of the zinc (II) center. After five cycles, the catalytic activities of CP 1 did not significantly decrease, and the structures remained unchanged. Therefore, the CP 1 was considered efficient and stable heterogeneous catalysts for above the two reactions.

A novel RAV transcription factor from pear interacts with viral RNA-silencing suppressors to inhibit viral infection.

In plants, RNA silencing constitutes a strong defense against viral infection, which viruses counteract with RNA-silencing suppressors (RSSs). Understanding the interactions between viral RSSs and host factors is crucial for elucidating the molecular arms race between viruses and host plants. We report that the helicase motif (Hel) of the replicase encoded by apple stem grooving virus (ASGV)-the main virus affecting pear trees in China-is an RSS that can inhibit both local and systemic RNA silencing, possibly by binding double-stranded (ds) siRNA. The transcription factor related to ABSCISIC ACID INSENSITIVE3/VIVIPAROUS1 from pear (PbRAV1) enters the cytoplasm and binds Hel through its C terminus, thereby attenuating its RSS activity by reducing its binding affinity to 21- and 24-nt ds siRNA, and suppressing ASGV infection. PbRAV1 can also target p24, an RSS encoded by grapevine leafroll-associated virus 2 (GLRaV-2), with similar negative effects on p24's suppressive function and inhibition of GLRaV-2 infection. Moreover, like the positive role of the PbRAV1 homolog from grapevine (VvRAV1) in p24's previously reported RSS activity, ASGV Hel can also hijack VvRAV1 and employ the protein to sequester 21-nt ds siRNA, thereby enhancing its own RSS activity and promoting ASGV infection. Furthermore, PbRAV1 neither interacts with CP, an RSS encoded by grapevine inner necrosis virus, nor has any obvious effect on CP's RSS activity. Our results identify an RSS encoded by ASGV and demonstrate that PbRAV1, representing a novel type of RAV transcription factor, plays a defensive role against viral infection by targeting viral RSSs.

Copper excess in psychiatric disorders: a focus on mood spectrum disorders and sex

BackgroundMeta-analyses show increased copper (Cu) levels in major depression disorder. However, the association of Cu biomarkers with clinical classification in other mental health disorders has not been fully explored. MethodsTo this aim, we compared an extensive panel of Cu biomarkers, composed of Cu, ceruloplasmin (Cp) Cp activity, Cp specific activity, Cu not bound to ceruloplasmin (non-Cp Cu, also known as ‘free’ copper) in 171 consecutive patients affected by psychiatric disorders and in 61 healthy controls (HC) using MANOVA adjusting for the effect of sex and age, and studied their association with the clinical scale outcomes at psychiatric examination, namely Global Assessment of Functioning, Clinical Global Impression, and Brief Psychiatric Rating Scale. Resultsindividuals with psychiatric disorders were classified as 109 patients affected by mood spectrum disorders (MSD), 20 patients with schizophrenia spectrum disorders (SSD), and 42 with personality disorders (PD). Cu and non-Cp Cu were increased in psychiatric individuals than in HC, which also differed among the patients stratified per the clinical classification, being higher in the MSD individuals. The analysis stratified for sex revealed that women from the patient group, and specifically from the MSD group, had increased levels of Cu and non-Cp Cu than healthy women, while no difference was revealed in men. A logistic regression model considering the effect of sex and age revealed that non-Cp Cu could explain 26 % increased odds of having MSD per µmol/L unit increase (OR = 1.26; p = 0.0008; 95 % CI 1.099–1.436), that reached 40 % when considering only women. This result was driven by non-Cp Cu that correctly classified 64.1 % MSD (70 % in women) individuals vs. HC in a decision tree model, with values higher than 2.1 µmol/L which could distinguish the majority of MSD patients (86.3 % MSD vs. 13.7 % HC in women). None of the biological variables under study correlated with outcomes of the clinical scales, substances, or alcohol abuse. ConclusionCurrent results suggest mild Cu toxicity in women with MSD, as revealed by a value of non-Cp Cu higher than 2.1 µmol/L, which can be further investigated to assess its potential diagnostic accuracy in bigger and longitudinal cohorts.

Evaluation of the Effective Cowpea [Vigna unguiculata (L.) Walp] Sprouting or Roasting for Pig Feeding

Background: The study investigated the effective roasting or sprouting of cowpeas (Vigna unguiculata) based on effects on in vitro digestibility (IVDMD), supported by measurement of key chemical components and trypsin inhibitor activity (TIA). Methods: The in vitro dry matter digestibility (IVDMD) of raw and all processed cowpeas were evaluated using standard, 3-step (gastric-ileal-colon) simulation of porcine digestion, modified for micro (0.5 g) sample digestion. Standard methods were employed to track processing effects on Ash, CP, Fat, ADF, NDF and trypsin inhibitor activity (TIA) at key processing points. Result: Sprouting for 2 and 3 days significantly decreased (p less than 0.05) gastric-ileal IVDMD while increasing (p less than 0.05) colon IVDMD. Total (steps 1-3) IVDMD increased (p less than 0.05) in 2-day (0.911) and 4-day (0.902) sprouts. The 20-minute cowpea roasting to 105°C terminal grain temperature resulted in high (p less than 0.05) step 3 and total IVDMD coefficients. The lowest (p greater than 0.05) total IVDMD was recorded in 15-minute (0.883) (95°C terminal grain temperature) roasts. In both experiments 1 and 2, quantitative changes in IVDMD were consistent with the changes in the chemical components (ADF, NDF, fat, CP, minerals) and trypsin inhibitor activity. In conclusion, the compartmental and total IVDMD and quantitative change in chemical components and TIA indicated 4 days sprouting and 20-minute (105°C) roasting were respectively most effective for cowpea processing.

Iridium complex immobilized on covalent triazine framework derived from biomass as a recyclable catalyst for the dehydrogenation of formic acid

The first example of covalent triazine frameworks derived from biomass was designed and synthesized. Furthermore, an iridium complex Cp*Ir@CTF-biomass was prepared by the coordinative immobilization of [Cp*IrCl2]2 on the synthesized covalent triazine framework. In the presence of Cp*Ir@CTF-biomass (0.03 mol % Ir), the reaction was carried out for 24 min at 80 °C and an almost complete dehydrogenation of formic acid with an initial TOF of 7627 h−1 was observed. Further experiments confirmed that heterogeneous catalyst Cp*Ir@CTF-biomass and its homogeneous analog [Cp*Ir(pyridine)Cl2] have approximate catalytic activity. Moreover, catalytic activity of Cp*Ir@CTF-biomass is well maintained during six runs.©2024 Elsevier Inc. All rights reserved.

Analytical Validation of Two Assays for Equine Ceruloplasmin Ferroxidase Activity Assessment.

Ceruloplasmin (Cp) assessment in biological samples exploits the oxidase activity of this enzyme against several substrates, such as p-phenylenediamine (p-P), o-dianisidine (o-D) and, most recently, ammonium iron(II) sulfate (AIS). Once developed in humans, these assays are often used in veterinary medicine without appropriately optimizing in the animal species of interest. In this study, two assays using AIS and o-D as substrates have been compared and validated for Cp oxidase activity assessment in horse's plasma. The optimization of the assays was performed mainly by varying the buffer pH as well as the buffer and the substrate molar concentration. Under the best analytical conditions obtained, the horse blood serum samples were treated with sodium azide, a potent Cp inhibitor. In the o-D assay, 500 µM sodium azide treatment completely inhibits the enzymatic activity of Cp, whereas, using the AIS assay, a residual analytical signal was still present even at the highest (2000 µM) sodium azide concentration. Even though the analytical values obtained from these methods are well correlated, the enzymatic activity values significantly differ when expressed in Units L-1. A disagreement between these assays has also been detected with the Bland-Altman plot, showing a progressive discrepancy between methods with increasing analytical values.

Cold plasma-222 nm UV: A new cold sterilizing method for food contact surfaces

This study was designed to develop a cold plasma +222 nm ultraviolet (CP + UV) sterilization device in the food industry. Response surface methodology was applied to evaluate the effects of three treatment conditions on the antibacterial activity of CP + UV. The optimum treatment conditions (plasma gas flow: 4 m3/min, irradiation distance: 4 cm, treatment time: 60 s) were selected to optimize the reactor parameters of CP and 222 nm UV sterilization equipment, and its effects against the growth of S. aureus on different food contact materials were investigated. Results showed that the antibacterial activity against S. aureus was strongest when the plasma was operated at 8.5 kHz, 2.5 W/cm2 with two net layers of electrodes arranged transversely at a distance of 5 cm between the plasma outlet plane and UV centerline plane. After 60 s of CP + UV treatment, the number of S. aureus on the glass sheet, polypropylene film, corrugated paper, and kraft paper decreased by 4.5, 4.1, 1.5, and 2.4, respectively (p < 0.05). In summary, a novel CP + UV device was developed, which can be used for sterilization on different food surfaces, which potentially contributes to the development of the food industries.

Camellia oleifera seeds cake: Polyphenol profile and in vitro antioxidant activities as determined by different harvest periods

Camellia oleifera seed oil is widely recognized for its high nutritional value. And a large amount of seed cake is produced as a by-product of oil extraction. Studies have shown that the polyphenol content of oil obtained from materials at different harvesting stages varies, but no study has examined changes in the polyphenols of seed cake (CP). In our study, the composition profiles of 44 polyphenols contained in CP were identified and 8 of them were quantified by UPLC-QTOF-MS/MS and HPLC-QQQ-MS/MS, respectively. The antioxidant activity of CP was evaluated by ABTS and FRAP methods in combination with the H2O2-induced oxidative damage model of RAW264.7 cells. The results showed that although the content of CPs in the four stages showed different trends, they all had good ABTS+ scavenging and FRAP-reducing abilities. Moreover, CP attenuated oxidative damage in cells by enhancing cell viability, increasing SOD activity, decreasing the contents of MDA and ROS, decreasing apoptosis, and inhibiting the activation of the NF-κB signaling pathway. Correlation results from Grey relational degree analysis and Pearson analysis showed that chlorogenic acid, 5, 7-dimethoxy-4'-hydroxyflavanone, and kaempferol-3-O-rutinoside contributed significantly to antioxidant activity. The results would provide a theoretical basis for the development and utilization of the added value of Camellia oleifera seed cake.

A new insight on copper: Promotion of collagen synthesis and myofiber growth and development in juvenile grass carp (Ctenopharyngodon idella)

Copper (Cu) is a trace element, essential for fish growth. In the current study, in addition to growth performance, we first explored the effects of Cu on collagen synthesis and myofiber growth and development in juvenile grass carp (Ctenopharyngodon idella). A total of 1080 fish (11.16 ± 0.01 g) were randomly divided into 6 treatments (3 replicates per treatment) to receive five doses of organic Cu, which were Cu citrate (CuCit) at 0.99 (basal diet), 2.19, 4.06, 6.15, and 8.07 mg/kg, and one dose of inorganic Cu (CuSO4·5H2O at 3.15 mg/kg), for 9 weeks. The results showed appropriate Cu level (4.06 mg/kg) enhanced growth performance, improved nutritional Cu status, and downregulated Cu-transporting ATPase 1 mRNA levels in the hepatopancreas, intestine, and muscle of juvenile grass carp. Meanwhile, collagen content in fish muscle was increased after Cu intake, which was probably due to the following pathways: (1) activating CTGF/TGF-β1/Smads signaling pathway to regulate collagen transcription; (2) upregulating of La ribonucleoprotein domain family 6 (LARP6) mRNA levels to regulate translation initiation; (3) increasing proline hydroxylase, lysine hydroxylase, and lysine oxidase activities to regulate posttranslational modifications. In addition, optimal Cu group increased myofiber diameters and the frequency of myofibers with diameter >50 μm, which might be associated with upregulation of cyclin B, cyclin D, cyclin E, proliferating cell nuclear antigen, myogenic determining factor (MyoD), myogenic factor 5, myogenin (MyoG), myogenic regulatory factor 4 and myosin heavy chain (MyHC) and downregulation of myostatin mRNA levels, increasing protein levels of MyoD, MyoG and MyHC in fish muscle. Finally, based on percentage weight gain (PWG), serum ceruloplasmin (Cp) activity and collagen content in fish muscle, Cu requirements were determined as 4.74, 4.37 and 4.62 mg/kg diet (CuCit as Cu source) of juvenile grass carp, respectively. Based on PWG and Cp activity, compared to CuSO4·5H2O, the efficacy of CuCit were 131.80% and 115.38%, respectively. Our findings provide new insights into Cu supplementation to promote muscle growth in fish, and help improve the overall productivity of aquaculture.

Determination of Ceruloplasmin Ferroxidase Activity, Iron &amp; Transferrin in Patients with Brain Tumor

Serum from healthy volunteers (n=30) was found to contain little ceruloplasmin (Cp) ferroxidase activity. Higher level of activity was found in the sera that obtained from patients (n=64) with benign and malignant brain tumors. The highest activity was measured in sera of malignant tumors patients. The differences were significant between Cp activity in sera of both type of patients in comparison to that of the control healthy group (p&lt;0.05), and between benign patients with that with malignant brain tumors (p&lt;0.01). Also the results of the current work illustrated the presence of a significant increase in [iron] (p&lt;0.01), as well as total iron binding capacity, in sera of the patients groups in comparison to that of healthy group. The increase in iron concentration was found to be accompanied with a significant decrease in transferrin concentration. This lead to an increase in the concentration of free iron, which is one of the pro oxidants that cause production of more free radicals.

Hexaazatrinaphthalene-Based Covalent Triazine Framework-Supported Rhodium(III) Complex: A Recyclable Heterogeneous Catalyst for the Reductive Amination of Ketones to Primary Amines.

The development of efficient and recyclable heterogeneous catalysts is an important topic. Herein, a rhodium(III) complex Cp*Rh@HATN-CTF was synthesized by the coordinative immobilization of [Cp*RhCl2]2 on a hexaazatrinaphthalene-based covalent triazine framework. In the presence of Cp*Rh@HATN-CTF (1 mo l% Rh), a series of primary amines could be obtained via the reductive amination of ketones in high yields. Moreover, catalytic activity of Cp*Rh@HATN-CTF is well maintained during six runs. The present catalytic system was also applied for the large scale preparation of a biologically active compound. It would facilitate the development of CTF-supported transition metal catalysts for sustainable chemistry.

The expression of ceruloplasmin in astrocytes is essential for postnatal myelination and myelin maintenance in the adult brain.

Ceruloplasmin (Cp) is a ferroxidase enzyme that is essential for cell iron efflux. The absence of this protein in humans and rodents produces progressive neurodegeneration with brain iron accumulation. Astrocytes express high levels of Cp and iron efflux from these cells has been shown to be central for oligodendrocyte maturation and myelination. To explore the role of astrocytic Cp in brain development and aging we generated a specific conditional KO mouse for Cp in astrocytes (Cp cKO). Deletion of Cp in astrocytes during the first postnatal week induced hypomyelination and a significant delay in oligodendrocyte maturation. This abnormal myelin synthesis was exacerbated throughout the first two postnatal months and accompanied by a reduction in oligodendrocyte iron content, as well as an increase in brain oxidative stress. In contrast to young animals, deletion of astrocytic Cp at 8 months of age engendered iron accumulation in several brain areas and neurodegeneration in cortical regions. Aged Cp cKO mice also showed myelin loss and oxidative stress in oligodendrocytes and neurons, and at 18 months of age, developed abnormal behavioral profiles, including deficits in locomotion and short-term memory. In summary, our results demonstrate that iron efflux-mediated by astrocytic Cp-is essential for both early oligodendrocyte maturation and myelin integrity in the mature brain. Additionally, our data suggest that astrocytic Cp activity is central to prevent iron accumulation and iron-induced oxidative stress in the aging CNS.

The Impact of Chitosan on Oxidative Stress in Liver of Rats Loaded With Lead Acetate

This study was conducted to determine the impact of chitosan on lead (Pb)-induced hepatotoxicity. Thus, lead acetate was administered intraperitoneally (50 mg/kg for 5 days) and chitosan was given as 200 mg/kg via oral gavage for 28 days. When the trial was terminated, it was determined that aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities in serum as well as Pb, 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels and catalase (CAT) activity in liver tissue significantly increased, however reduced glutathione (GSH) and ceruloplasmin (Cp) levels in liver and high density lipoproteins (HDL) in serum had a significant decrease in the Pb group when compared to the control group. The administration of chitosan significantly prevented Pb-induced changes in serum liver enzyme activities, 8-OHdG and MDA levels. In addition, chitosan showed a statistically insignificant effect on reduced GSH, Cp, HDL levels and CAT activity. Accordingly, administration of chitosan can strengthen the antioxidant defence system of liver tissue and may decrease oxidative stress.

Distinction of early complement classical and lectin pathway activation via quantification of C1s/C1-INH and MASP-1/C1-INH complexes using novel ELISAs.

The most commonly used markers to assess complement activation are split products that are produced through activation of all three pathways and are located downstream of C3. In contrast, C4d derives from the cleavage of C4 and indicates either classical (CP) or lectin pathway (LP) activation. Although C4d is perfectly able to distinguish between CP/LP and alternative pathway (AP) activation, no well-established markers are available to differentiate between early CP and LP activation. Active enzymes of both pathways (C1s/C1r for the CP, MASP-1/MASP-2 for the LP) are regulated by C1 esterase inhibitor (C1-INH) through the formation of covalent complexes. Aim of this study was to develop validated immunoassays detecting C1s/C1-INH and MASP-1/C1-INH complex levels. Measurement of the complexes reveals information about the involvement of the respective pathways in complement-mediated diseases. Two sandwich ELISAs detecting C1s/C1-INH and MASP-1/C1-INH complex were developed and tested thoroughly, and it was investigated whether C1s/C1-INH and MASP-1/C1-INH complexes could serve as markers for either early CP or LP activation. In addition, a reference range for these complexes in healthy adults was defined, and the assays were clinically validated utilizing samples of 414 COVID-19 patients and 96 healthy controls. The immunoassays can reliably measure C1s/C1-INH and MASP-1/C1-INH complex concentrations in EDTA plasma from healthy and diseased individuals. Both complex levels are increased in serum when activated with zymosan, making them suitable markers for early classical and early lectin pathway activation. Furthermore, measurements of C1-INH complexes in 96 healthy adults showed normally distributed C1s/C1-INH complex levels with a physiological concentration of 1846 ± 1060 ng/mL (mean ± 2SD) and right-skewed distribution of MASP-1/C1-INH complex levels with a median concentration of 36.9 (13.18 - 87.89) ng/mL (2.5-97.5 percentile range), while levels of both complexes were increased in COVID-19 patients (p<0.0001). The newly developed assays measure C1-INH complex levels in an accurate way. C1s/C1-INH and MASP-1/C1-INH complexes are suitable markers to assess early classical and lectin pathway activation. An initial reference range was set and first studies showed that these markers have added value for investigating and unraveling complement activation in human disease.

Molybdenum fertilizer improved antioxidant capacity of Chinese Merino sheep under compound contamination.

To investigate the response of different levels of molybdenum (Mo) fertilizer to Chinese Merino sheep (Junken Type) grazing on natural heavy metal-contaminated meadows, this study was carried out in the Bayanbulak Grassland lying in the northwest of Xinjiang Uygur Autonomous Region, China. A total of 24-hm2 polluted meadows were fenced and were randomly divided into four groups (3 replication/group and 2 hm2/replication) applied 0-kg Mo, 1-kg Mo, 2-kg Mo, and 3-kg Mo (ammonium molybdate tetrahydrate) per hectare for the CON group, group I, group II, and group III, respectively. Seventy-two healthy 1-year-old Chinese Merino sheep (45.56 ± 2.35 kg) were randomly assigned to the tested pastures for 90 days. Compared with the CON group, the Mo content from fertilized groups and the Se content from group II and group III in serums and livers were significantly increased (P < 0.05), and the Cu content from fertilized groups in serums and livers was significantly decreased (P < 0.05). The levels of blood Hb and RBC, and the activities of serum SOD, CAT, GSH-Px, and Cp in group III, were significantly higher (P < 0.05) than those in the CON group, group I, and group II. Serum MDA content in group III was significantly lower (P < 0.05) than that in the other three groups. In summary, Mo fertilization improved the antioxidant capacity of grazing sheep and also reduced the toxic damage to Chinese Merino sheep grazing on natural grasslands contaminated by heavy metals, but Mo poisoning caused by excessive fertilization should be prevented.

Combining VA-ECMO and Impella (EC-Pella) Before Reperfusion Mitigates Left Ventricular Injury Due to VA-ECMO in Acute Myocardial Infarction

<h3>Purpose</h3> Combining veno-arterial extracorporeal membrane oxygenation (ECMO) with an Impella CP (EC-Pella) is increasingly used in acute myocardial infarction (AMI). We recently reported that compared to reperfusion alone, ECMO increases, but Impella decreases infarct size in preclinical models. Whether EC-Pella limits cardiac damage remains unknown. We hypothesized that compared to ECMO alone, EC-Pella mitigates left ventricular (LV) injury when activated before reperfusion in AMI. <h3>Methods</h3> Ischemia-reperfusion injury (IRI) was induced in adult swine via percutaneous occlusion of the left anterior descending artery (LAD) for 120 minutes. We then activated either ECMO alone for 30 minutes or EC-Pella for 45 minutes with persistent LAD occlusion. All groups underwent 180 minutes of reperfusion (n=4-6/group). To study whether the sequence of device activation impacts infarct size, we compared activation of ECMO alone for 30 minutes followed by simultaneous Impella CP for 15 minutes (EC-Pella A) versus Impella CP activation for 30 minutes followed by simultaneous ECMO for 15 minutes (EC-Pella B) before reperfusion. LV hemodynamics, infarct size relative to the area at risk (IS) and cardioprotective signaling were assessed. <h3>Results</h3> Compared to IRI, ECMO increased IS. Compared to ECMO, IS was reduced in both EC-Pella groups (Fig. 1A). No difference in IS was observed between EC-Pella A versus EC-Pella B. Pressure-volume area (PVA) was lowest in EC-Pella B (Fig. 1B). Compared to IRI and ECMO, both EC-Pella configurations increased levels of phosphorylated Akt, Erk, and GSK3b within the infarct zone (Fig. 1C) and reduced pro-apoptotic signaling. <h3>Conclusion</h3> We report for the first time that compared to ECMO alone, initiation of EC-Pella before reperfusion reduces LV PVA, activates cardioprotective signaling, and reduces infarct size. These findings suggest that LV unloading may mitigate LV injury due to ECMO when applied before reperfusion in AMI.

Chemical Variation of Chenpi (Citrus Peels) and Corresponding Correlated Bioactive Compounds by LC-MS Metabolomics and Multibioassay Analysis.

The peel of Citrus reticulata “Chachi” (CP) possesses various health-promoting benefits and is not only one of the most famous Chinese herbal medicine, but also an ingredient in fermented foods. In the present study, the effects of storage years (1-, 3-, 4-, 5-, 6-, and 11-years) on the chemical profiling and potential bioactive compounds of CP were compared by metabolomics and in vitro bioactivity analysis. With the increase of storage time, the content of hesperidin significantly decreased, but nobiletin, 3,5,6,7,8,3′,4′-heptamethoxyflavone, and tangeretin were increased. Meanwhile, the antioxidant activity of CP was enhanced. Phenolic acids, flavonol glycosides, fatty acids, and alkyl glycosides were marker compounds that were responsible for distinguishing the storage time of CP. Correlation analysis suggested that some polyphenols including quercetin-glucoside, quinic acid, trihydroxydimethoxyflavone, and rutin were potential antioxidant compounds in CP. The dichloromethane and n-butanol fractions showed the better antioxidant capacity and inhibitory effects on glucose-hydrolysis enzymes. They mainly contained ferulic acid, nobiletin, 3,5,6,7,8,3′,4′-heptamethoxyflavone, kaempferol, and hesperidin.

Oleic amide derivatives as small molecule stimulators of the human proteasome's core particle.

A series of oleic acid amide derivatives were synthesized based on our previous and continuing endeavors towards stimulation of the 20S core particle of the proteasome (20S CP) with the goal of increasing the protein degradation rate via the ubiquitin-independent pathway. The designed compounds were tested in a variety of biochemical and cell-based assays to assess their ability to increase the rate of hydrolysis of the 20S CP, and compared to a known fatty acid amide stimulator of the 20S CP, AM-404. AM-404 was previously described to stimulate the activity of the 20S CP, however, it does negatively affect viability of cells after prolonged dosing. Here we report the development of several small molecules with a similar ability to enhance the activity of the 20S CP as AM-404. While one molecule (17) was just as potent as AM-404, it still caused significant unwanted cytotoxicity. Molecules such as these are compatible with biochemical assays and short-term cell-based proteasome activity assays, but their unwanted toxicity limits their use in prolonged cell assays or in vivo studies.

A Unified Genomic Mechanism of Cell-Fate Change.

The purpose of our studies is to elucidate the nature of massive control of the whole genome expression with a particular emphasis on cell-fate change. The whole genome expression is coordinated by the emergence of a critical point (CP: a peculiar set of biphasic genes) with the genome acting as an integrated dynamical system. In response to stimuli, the genome expression self-organizes into localsub-, near-, and super-critical states, each exhibiting distinct collective behaviors with its center of mass acting as a local attractor, coexisting with the whole genome attractor (GA). The CP serves as the organizing center of cell-fate change, and its activation makes local perturbation to spread over the genome affecting GA. The activation of CP is in turn elicited by genes with elevated temporal variance (oscillating-mode genes), normally in charge to keep genome expression at pace with microenvironment fluctuations. When oscillation exceeds a given threshold, the CP synchronizes with the GA driving genome expression state transition. The expression synchronization wave invading the entire genome is fostered by the fusion-splitting dynamics of silencing pericentromere-associated heterochromatin domains and the consequent folding-unfolding transitions of transcribing euchromatin domains. The proposed mechanism is a unified step toward a time-evolutional transition theory of biological regulation.

Stimulation Of Neutrophil Oxidative Burst By Calcium Phosphate Particles With Adsorbed Mucin

Objective — Mucin can promote formation of gallstones via precipitation with calcium phosphate. The proinflammatory effect of mucin-coated particles is still unclear, and our aim was to study the role of mucin sorption in activation of neutrophil respiratory burst. Material and Methods — Polydisperse calcium phosphate nanowires (CP) were prepared from hot gelatin solution and according to scanning electron microscopy (SEM) had the length 1-10 μm and thickness 50-450 nm. CP were incubated in mucin or human serum albumin (HSA) giving CP-Muc and CP-HSA. Their hemolytic activity towards human erythrocytes was assayed, and neutrophil lucigenin- and luminol- chemiluminescence (Luc-CL and Lum-CL) response to CP, CP-HSA and CP-Muc was measured. Cytokine RNA was detected in neutrophils by means of reverse transcription with subsequent real-time PCR. Cytokines (IL-1β, IL-6, IL-8, IL-10) were assessed in cell medium by ELISA. Results and Conclusion — Hemolytic activity of CP was 3.0±0.5%, mucin sorption (0.019 mg/mg) reduced it to 0.24±0.04% (p&lt;0.05) as well as HSA. CP and CP-HSA stimulated neutrophil Lum-CL and Luc-Cl by 2-3 times vs. spontaneous values while for CP-Muc the effect was 10-fold and higher. No increased cytokine gene expression or cytokine secretion was detected after 1h incubation of neutrophils with samples. Obviously, sorption of mucin but not that of HSA stimulated generation of reactive oxygen and halogen species with no increase in cytokine production. Thus, the mucin-coated CP has the potential to contribute to gallstone-associated cholecystitis via oxidative damage of mucosa and epithelium.