Input: Epidemiological investigations suggest a link between exposure to indoor air chemicals and adverse health effects.


Input: Consumer products contain reactive chemicals which can form secondary pollutants which may contribute to these effects.


Input: The reaction of limonene and ozone is a well characterized example of this type of indoor air chemistry.

limonene

ozone


Input: The studies described here characterize an in vitro model using an epithelial cell line (A549) or differentiated epithelial tissue (MucilAir (TM)).


Input: The model is used to investigate adverse effects following exposure to combinations of limonene and ozone.

limonene

ozone


Input: In A549 cells, exposure to both the parent compounds and reaction products resulted in alterations in inflammatory cytokine production.


Input: A one hour exposure to limonene + ozone resulted in decreased proliferation when compared to cells exposed to limonene alone.

limonene

ozone

limonene


Input: Repeated dose exposures of limonene or limonene + ozone were conducted on MucilAir (TM) tissue.

limonene

limonene

ozone


Input: No change in proliferation was observed but increases in cytokine production were observed for both the parent compounds and reaction products.


Input: Factors such as exposure duration, chemical concentration, and sampling time point were identified to influence result outcome.


Input: These findings suggest that exposure to reaction products may produce more severe effects compared to the parent compound.


Input: Brain monoamines and antidepressant-like responses in MRL/MpJ versus C57BL/6J mice.

monoamines


Input: The MRL/MpJ mouse demonstrates enhanced wound healing and tissue regeneration and increased neurotrophic mobilization to chronic antidepressant drug treatments.


Input: This study compared brain monoamine systems between MRL/MpJ and C57BL/6J mice as a potential basis for strain differences after chronic antidepressant treatment.

monoamine


Input: MRL/MpJ mice had significantly higher tissue levels of serotonin and dopamine in multiple brain regions.

serotonin

dopamine


Input: Microdialysis studies demonstrated that baseline levels of extracellular serotonin did not differ between strains.

serotonin


Input: However, acute administration of the selective serotonin reuptake inhibitor citalopram produced an increase in extracellular serotonin in the ventral hippocampus of MRL/MpJ mice that was twice as large as achieved in C57BL/6J mice.

serotonin

citalopram

serotonin


Input: The greater effects in MRL/MpJ mice on 5-HT levels were not maintained after local perfusion of citalopram, suggesting that mechanisms outside of the hippocampus were responsible for the greater effect of citalopram after systemic injection.

citalopram

citalopram


Input: The density of serotonin and norepinephrine transporters in the hippocampus was significantly higher in MRL/MpJ mice.

serotonin

norepinephrine


Input: In addition, the expression of 5-HT (1A) mRNA was lower in the hippocampus, 5-HT (1B) mRNA was higher in the hippocampus and brainstem and SERT mRNA was higher in the brain stem of MRL/MpJ mice.


Input: The exaggerated neurotransmitter release in MRL/MpJ mice was accompanied by reduced baseline immobility in the tail suspension test and a greater reduction of immobility produced by citalopram or the tricyclic antidepressant desipramine.

citalopram

desipramine


Input: These data suggest that differences in the response to acute and chronic antidepressant treatments between the two strains could be attributed to differences in serotonin or catecholamine transmission.

serotonin

catecholamine


Input: Effects of adolescent social defeat on adult amphetamine-induced locomotion and corticoaccumbal dopamine release in male rats.

amphetamine

dopamine


Input: Maturation of mesocorticolimbic dopamine systems occurs during adolescence, and exposure to social stress during this period results in behavioral dysfunction including substance abuse disorders.

dopamine


Input: Adult male rats exposed to repeated social defeat in adolescence exhibit reduced basal dopamine tissue content in the medial prefrontal cortex, altered dopamine tissue content in corticoaccumbal dopamine regions following acute amphetamine, and increased amphetamine conditioned place preference following repeated amphetamine treatment.

dopamine

dopamine

dopamine

amphetamine

amphetamine

amphetamine


Input: Such changes may reflect altered amphetamine-induced extracellular dopamine release in the corticoaccumbal regions.

amphetamine

dopamine


Input: Therefore, we used in vivo microdialysis to measure extracellular dopamine simultaneously within the medial prefrontal cortex and nucleus accumbens core of previously defeated rats and controls, in response to either acute or repeated (7 daily injections) of amphetamine (1. 0 mg/kg).

dopamine

amphetamine


Input: Locomotion responses to acute/repeated amphetamine were also assessed the day prior to taking dopamine measurements.

amphetamine

dopamine


Input: Adolescent defeat potentiated adult locomotion responses to acute amphetamine, which was negatively correlated with attenuated amphetamine-induced dopamine release in the medial prefrontal cortex, but there was no difference in amphetamine-induced accumbal dopamine release.

amphetamine

amphetamine

dopamine

amphetamine

dopamine


Input: However, both locomotion and corticoaccumbal dopamine responses to repeated amphetamine were equivalent between previously defeated rats and controls.

dopamine

amphetamine


Input: These data suggest adolescent defeat enhances behavioral responses to initial amphetamine exposure as a function of diminished prefrontal cortex dopamine activity, which may be sufficient to promote subsequently enhanced seeking of drug-associated cues.

amphetamine

dopamine


Input: Interestingly, repeated amphetamine treatment appears to normalize amphetamine-elicited locomotion and cortical dopamine responses observed in adult rats exposed to adolescent social defeat, providing implications for treating stress-induced dopamine dysfunction.

amphetamine

amphetamine

dopamine

dopamine


Input: Comparative responses of two species of marine phytoplankton to metolachlor exposure.

metolachlor


Input: Metolachlor, a chloroacetanilide herbicide, has been frequently detected in coastal waters.

Metolachlor

chloroacetanilide


Input: This study examined the growth, photosynthesis, and detoxification responses of chlorophyte Dunaliella tertiolecta (DT) and brown tide alga Aureococcus anophagefferens (AA) upon 5-day exposure to 0. 5-5 mg L (-1) metolachlor.

metolachlor


Input: Growth was assessed with exponential growth rate, and 5th day in vivo chlorophyll fluorescence, chlorophyll a, b or c, cell density and cell size.

chlorophyll a, b or c


Input: The photosynthesis function was assessed with photochemical parameters of photosystem II (PSII) during the mid-exponential growth phase (i. e. 2-4 day metolachlor exposure).

metolachlor


Input: The biochemical detoxification was analyzed with glutathione production and metolachlor degradation.

glutathione

metolachlor


Input: Results show that metolachlor caused up to ~ 9% inhibition in growth rate in both species and an expected ~ 35% and 25% inhibition in chlorophyll based endpoints in DT and AA respectively.

metolachlor


Input: DT had an up to 70% inhibition in cell density, but AA a 35% hormesis at 1 mg L (-1) metolachlor and no significant inhibition, as compared to the controls.

metolachlor


Input: Both DT and AA' s cell sizes were enlarged by metolachlor exposure, but greater in DT (1. 2% per mg L (-1)) than in AA (0. 68% per mg L (-1)).

metolachlor


Input: On PSII photochemistry, maximum quantum yield was not affected in both species; PSII optical cross section and connectivity factor increased in DT but decreased in AA, suggesting species specific impact on PSII function.


Input: On detoxification responses, glutathione production, when normalized to total chlorophyll a, was not affected by metolachlor in both species; further, despite of heterotrophic capacity of A. anophagefferens metolachlor was not significantly degraded by this alga during the 5-day incubation.

glutathione

chlorophyll a

metolachlor

metolachlor


Input: The species specific effects on algal growth have ecological implications of potential selective inhibition of chlorophytes by metolachlor herbicide.

metolachlor


Input: Exposure of zebrafish embryos/larvae to TDCPP alters concentrations of thyroid hormones and transcriptions of genes involved in the hypothalamic-pituitary-thyroid axis.

TDCPP


Input: Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in the environment and in various biota, including fish, and has been implicated in disruption of the thyroid endocrine system.

Tris (1, 3-dichloro-2-propyl) phosphate

TDCPP


Input: In the present study, zebrafish (Danio rerio) embryos were exposed to different concentrations of TDCPP (10, 50, 100, 300 and 600 mu g/L) from 2 h post-fertilization (hpf) to 144 hpf.

TDCPP


Input: Developmental endpoints, and whole-body concentrations of thyroid hormones and transcriptional profiles of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined.


Input: Exposure to TDCPP caused a dose-dependent developmental toxicity, including decreased body weight, reduced hatching, survival and heartbeat rates, and increased malformation (spinal curvature).

TDCPP


Input: Treatment with the positive control chemical 3, 3', 5-triiodo-l-thyronine (T3) significantly decreased whole-body thyroxin (T4) concentrations, increased whole-body T3 concentrations, and upregulated mRNA expression involved in the HPT axis as a compensatory mechanism.

3, 3', 5-triiodo-l-thyronine

thyroxin (T4)


Input: These results suggested that the HPT axis in 144-hpf zebrafish larvae was responsive to chemical exposure and could be used to evaluate the effects of chemicals on the thyroid endocrine system.


Input: TDCPP exposure significantly decreased whole-body T4 concentrations and increased whole-body T3 concentrations, indicating thyroid endocrine disruption.

TDCPP


Input: The upregulation of genes related to thyroid hormone metabolism (dio1 and ugt1ab) might be responsible for decreased T4 concentrations.


Input: Treatment with TDCPP also significantly increased transcription of genes involved in thyroid hormone synthesis (tsh beta, slc5a5 and tg) and thyroid development (hhex, nkx2. 1 and pax8) as a compensatory mechanism for decreased T4 concentrations.

TDCPP


Input: Taken together, these results suggest that TDCPP alters the transcription of genes involved in the HPT axis and changes whole-body concentrations of thyroid hormones in zebrafish embryos/larvae, thus causing an endocrine disruption of the thyroid system.

TDCPP


Input: Methyleugenol hepatocellular cancer initiating effects in rat liver.

Methyleugenol


Input: Methyleugenol (MEG), a constituent of plants used in the human diet, is hepatocarcinogenic in rodents.

Methyleugenol

MEG


Input: In an experiment to elucidate its mode of action in rat liver, male F344 rats were administered MEG intragastrically at 3 doses per week for up to 16 weeks in an initiation phase, after which half the rats were fed 500 ppm phenobarbital (PB) in the diet to promote liver neoplasia and the other half were maintained on control diet for 24 weeks.

MEG

phenobarbital


Input: At 8 and 16 week interim terminations, (32) P-nucleotide postlabeling assay revealed 3 adducts in livers of all MEG groups.

(32) P

MEG


Input: The hepatocellular replicating fractions, measured by proliferating cell nuclear antigen immunohistochemistry, were doubled or more in all MEG groups.

MEG


Input: Hepatocellular altered foci, detected by glutathione S-transferase-placental type (pi) immunohistochemistry, were present beginning with the high dose group at 8 weeks and extending to all MEG groups at 16 weeks.

glutathione S

MEG


Input: At the end of maintenance/promotion phase, the incidences, multiplicity and size of foci was similar between control and low dose groups, while those of mid and high dose groups were increased.


Input: Hepatocellular adenomas occurred in the mid and high dose groups, attaining higher multiplicity and size with PB.


Input: Thus, MEG had rapid initiating activity, reflecting the formation of DNA adducts and possibly cell proliferation.

MEG


Input: Effect of linalool as a component of Humulus lupulus on doxorubicin-induced antitumor activity.

linalool

doxorubicin


Input: As malignant neoplasm is a major public health problem, there is a need for the development of a novel modulator that enhances antitumor activity and reduces adverse reactions to antitumor agents.


Input: In this study, the effects of some volatile oil components in Humulus lupulus on doxorubicin (DOX) permeability in tumor cells and DOX-induced antitumor activity were examined.

doxorubicin

DOX

DOX


Input: In vitro, DOX levels in tumor cells by combined linalool as its component significantly increased in the DOX influx system, and the increased effect by linalool on DOX cytotoxicity was shown.

DOX

linalool

DOX

linalool

DOX


Input: In vivo, the combination of DOX with linalool significantly decreased tumor weight compared with that of DOX alone treated group.

DOX

linalool

DOX


Input: The promotion of DOX influx level by combined linalool did not depend on energy, whereas it was suppressed by the absence of Na (+).

DOX

linalool

Na (+)


Input: This promoting effect was suppressed by the presence of S-(4-nitrobenzyl)-6-thioinosine and inhibited dependently on phlorizin concentration.

phlorizin


Input: It is considered that linalool promoted DOX influx in tumor cells because of its action on DOX transport through concentrative Na (+)-dependent nucleoside transporter 3, which increased DOX concentration in tumor cells and thus enhanced the antitumor activity of DOX.

linalool

DOX

DOX

Na (+)

nucleoside

DOX

DOX


Input: Therefore, linalool as a food component is anticipated to be an effective DOX modulator.

linalool

DOX


Input: Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex.

methylmercury


Input: We determined the effects of low-level prenatal MeHg exposure on neuronal migration in the developing rat cerebral cortex using in utero electroporation.

MeHg


Input: We used offspring rats born to dams that had been exposed to saline or various doses of MeHg (0. 01 mg/kg/day, 0. 1 mg/kg/day, and 1 mg/kg/day) from gestational day (GD) 11-21.

MeHg


Input: Immunohistochemical examination of the brains of the offspring was conducted on postnatal day (PND) 0, PND3, and PND7.


Input: Our results showed that prenatal exposure to low levels of MeHg (0. 1 mg/kg/day or 1 mg/kg/day) during the critical stage in neuronal migration resulted in migration defects of the cerebrocortical neurons in offspring rats.

MeHg


Input: Importantly, our data revealed that the abnormal neuronal distribution induced by MeHg was not caused by altered proliferation of neural progenitor cells (NPCs), induction of apoptosis of NPCs and/or newborn neurons, abnormal differentiation of NPCs, and the morphological changes of radial glial scaffold, indicating that the defective neuronal positioning triggered by exposure to low-dose of MeHg is due to the impacts of MeHg on the process of neuronal migration itself.

MeHg

MeHg

MeHg


Input: Moreover, we demonstrated that in utero exposure to low-level MeHg suppresses the expression of Rac1, Cdc42, and RhoA, which play key roles in the migration of cerebrocortical neurons during the early stage of brain development, suggesting that the MeHg-induced migratory disturbance of cerebrocortical neurons is likely associated with the Rho GTPases signal pathway.

MeHg

MeHg


Input: In conclusion, our results provide a novel perspective on clarifying the mechanisms underlying the impairment of neuronal migration induced by MeHg.

MeHg


Input: Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation.

clopidogrel


Input: Bleeding complications and delayed healing of gastric ulcer associated with use of clopidogrel is a common clinical concern; however, the underlying mechanisms remain to be determined.

clopidogrel


Input: This study aimed to clarify whether clopidogrel could cause the damage of the human gastric epithelial cells and to further elucidate the mechanisms involved.

clopidogrel


Input: After human gastric epithelial cell line GES-1 had been treated with clopidogrel (0. 5-2. 5 mM), the cell proliferation was examined by MTT assay, apoptosis was measured with DAPI staining and flow cytometry analysis, and the barrier function of the tight junctions (TJ) was evaluated by permeability measurement and transmission electron microscopy.

clopidogrel

MTT

DAPI


Input: Moreover, expression of the TJ proteins occludin and ZO-1 and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38, ERK, and JNK were examined by western blot.


Input: In addition, three MAPK inhibitors specific to p38, ERK and JNK were used, respectively, to verify the signaling pathways responsible for regulating the expression of the TJ proteins being tested.


Input: Results showed that clopidogrel significantly increased dextran permeability, induced apoptosis, suppressed GES-1 cell viability, and reduced the expression of the TJ proteins (occludin and ZO-1), acting through p38 MAPK phosphorylation.

clopidogrel


Input: Furthermore, these observed effects were partially abolished by SB-203580 (a p38 MAPK inhibitor), rather than by either U-0126 (an ERK inhibitor) or SP-600125 (a JNK inhibitor), suggesting that clopidogrel-induced disruption in the gastric epithelial cells is mediated by the p38 MAPK pathway.

clopidogrel


Input: It is concluded that attenuated expression of the TJ proteins occludin and ZO-1 in human gastric epithelial cells could be involved in clopidogrel-induced gastric mucosal injury through activation of the p38 MAPK pathway.

clopidogrel


Input: Effect of polyethylene glycol conjugation on the circulatory stability of plasma-derived human butyrylcholinesterase in mice.

polyethylene glycol


Input: Exogenously administered human serum butyrylcholinesterase (Hu BChE) was demonstrated to function as a bioscavenger of highly toxic organophosphorus (OP) compounds in several animal species.

organophosphorus


Input: Since the enzyme is isolated from human serum, it is currently the most suitable pretreatment for human use.


Input: A dose of 200-300mg/70kg human adult is projected to provide protection from 2 X LD50 of soman.

soman


Input: Due to the limited supply of Hu BChE, strategies aimed at reducing the dose of enzyme are being explored.


Input: In this study, we investigated the effect of modification with polyethylene glycol (PEG) on the in vivo stability of Hu BChE.

polyethylene glycol

PEG


Input: Mice were given two injections of either Hu BChE or Hu BChE modified with PEG-5K or PEG-20K, six weeks apart.

PEG

PEG


Input: Pharmacokinetic parameters, such as mean residence time (MRT), maximal concentration (Cmax), elimination half-life (T1/2), and area under the plasma concentration time curve extrapolated to infinity (AUC), were determined.


Input: For the first injection, values for MRT, T1/2, Cmax, and AUC for PEG-5K-Hu BChE and PEG-20K-Hu BChE were similar to those for Hu BChE.

PEG

PEG


Input: These values for the second injection of Hu BChE as well as PEG-Hu BChEs were lower as compared to those for the first injections, likely due to antibody-mediated clearance.

PEG


Input: Acrolein and chloroacetaldehyde: an examination of the cell and cell-free biomarkers of toxicity.

Acrolein

chloroacetaldehyde


Input: Cyclophosphamide and ifosfamide are two commonly used DNA-alkylating agents in cancer chemotherapy that undergo biotransformation to several toxic and non-toxic metabolites, including acrolein and chloroacetaldehyde (CAA).

Cyclophosphamide

ifosfamide

acrolein

chloroacetaldehyde

CAA


Input: Acrolein and CAA toxicities occur by several different mechanisms, including ROS formation and protein damage (oxidation), however, these pathways of toxicity and protecting agents used to prevent them have yet to be compared and ranked in a single study.

Acrolein

CAA


Input: This research focused on the molecular targets of acrolein and CAA toxicities and strategies to decrease toxicities.

acrolein

CAA


Input: Hepatocyte viability (cytotoxicity) was assessed using Trypan blue uptake; formation of reactive oxygen species (ROS) and endogenous H2O2 were also assessed in the hepatocyte model.

Trypan blue

oxygen


Input: In cell-free models (bovine serum albumin and hepatic microsomes), protein carbonylation was the measurement of toxicity.


Input: The present study demonstrated that acrolein was a more potent toxin than CAA for freshly isolated rat hepatocytes, bovine serum albumin and rat hepatic microsomes.

acrolein

CAA


Input: Acrolein protein carbonylation was dependent on its concentration; as acrolein concentration increased, protein carbonylation increased in a linear trend, whereas, CAA deviated from the trend and did not cause protein carbonylation at lower concentrations (< 400 mu M).

Acrolein

acrolein

CAA


Input: Aldehyde dehydrogenase (ALDH) is a major pathway for detoxifying pathway for CAA in hepatocytes, as a 3-fold increase in cytotoxicity occurred when cells were incubated with cyanamide, an ALDH inhibitor.

Aldehyde

CAA

cyanamide


Input: Inhibiting ALDH or depleting GSH in hepatocytes increased cytotoxicity by about 3-fold in acrolein-treated hepatocytes.

acrolein


Input: The overall effectiveness of protecting agents to prevent or suppress acrolein or CAA toxicities in cell and cell-free models were ranked in order of most effective to least effective: reducing agents (sodium borohydride, sodium bisulfite) > thiol-containing compounds (N-acetylcysteine, cysteine, glutathione, 2-mercaptoethane sulfonate [MESNA], penicillamine) > carbonyl scavengers/amines (aminoguanidine, hydralazine, hydroxylamine) > antioxidants/ROS scavengers (ascorbic acid, Trolox; only utilized in hepatocyte system).

acrolein

CAA

sodium borohydride

sodium bisulfite

thiol

N-acetylcysteine

cysteine

glutathione

2-mercaptoethane sulfonate

MESNA

penicillamine

carbonyl

amines

aminoguanidine

hydralazine

hydroxylamine

ascorbic acid

Trolox


Input: An understanding of acrolein and CAA toxicities and the ability of protecting agents to protect against toxicities may help to establish or improve existing therapeutic interventions against the side effects associated with acrolein or CAA in cyclophosphamide or ifosfamide treatment.

acrolein

CAA

acrolein

CAA

cyclophosphamide

ifosfamide


Input: In vitro investigation of efficacy of new reactivators on OPC inhibited rat brain acetylcholinesterase.


Input: Organophosphorus compounds (OPC) were developed as warfare nerve agents.

Organophosphorus


Input: They are also widely used as pesticides.


Input: The drug therapy of intoxication with OPC includes mainly combination of cholinesterase (ChE) reactivators and cholinolytics.


Input: There is no single ChE reactivator having an ability to reactivate sufficiently the inhibited enzyme due to the high variability of chemical structure of the inhibitors.


Input: The difficulties in reactivation of ChE activity and slight antidote effect regarding intoxication with some OPC are some of the reasons for continuous efforts to obtain new reactivators of ChE.


Input: The aim of the present study was to evaluate the efficacy of some ChE reactivators against OPC intoxication (tabun, paraoxon and dichlorvos) in in vitro experiments and to compare their activity to that known for some currently used oximes (obidoxime, HI-6, 2-PAM).

tabun

paraoxon

dichlorvos

oximes

obidoxime


Input: Experiments were carried out using rat brain acetylcholinesterase (AChE).


Input: Reactivators showed different activity in the reactivation of rat brain AChE after dichlorvos, paraoxon and tabun inhibition.

dichlorvos

paraoxon

tabun


Input: AChE was easier reactivated after paraoxon treatment.

paraoxon


Input: The best effect showed BT-07-4M, obidoxime, TMB-4 and BT-08 from the group of symmetric oximes, and Toxidin, BT-05 and BT-03 from asymmetric compounds.

obidoxime

oximes

Toxidin


Input: The reactivation of brain AChE inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure.

obidoxime

oximes


Input: All compounds showed low activity toward inhibition of AChE caused by dichlorvos.

dichlorvos


Input: Comparison of two main structure types (symmetric/asymmetric) showed that the symmetric compounds reactivated better AChE, inhibited with this OPC, than asymmetric ones.


Input: Profiling of oxidized lipid products of marine fish under acute oxidative stress.


Input: Free radical products including reactive oxygen species are potent to oxidize lipids and reliable measurements have been established mostly in human and rodent.

oxygen


Input: To date, robust biomarkers were not used to assess the peroxidation in marine fish.


Input: The changes of oxidized lipid products from polyunsaturated fatty acids and cholesterol were assessed after exposure of H (2) O (2) to fish (medaka).

polyunsaturated fatty acids

cholesterol

H (2) O (2)


Input: Oxidized lipid products released by free radical reaction (F (2)-isoprostanes and metabolites, F (3)-isoprostanes, neuroprostanes, 7-ketocholesterol, 7 beta-hydroxycholesterol), by lipoxygenase enzymes (5 (S)-, 8 (S)-, 12 (S)-and 15 (S)-HETE, and resolvin D1) and by cytochrome P450 (9 (S)-, 11 (S)-and 20-HETE, and 27-hydroxycholestrol) were measured in fish muscle using LC/MS/MS.

isoprostanes

isoprostanes

neuroprostanes

7 beta-hydroxycholesterol

5 (S)-, 8 (S)-, 12 (S)-and 15 (S)-HETE

resolvin D1

9 (S)-, 11 (S)-and 20-HETE


Input: Arachidonate, docosahexaenoate, eicosapentaenoate and cholesterol levels, and antioxidant enzymes activity (catalase, SOD and gluthathione reductase) measurement were also determined.

Arachidonate

docosahexaenoate

eicosapentaenoate

cholesterol

gluthathione


Input: Activity of antioxidant enzymes especially catalase were elevated in presence of H (2) O (2) however longer exposure time suppressed the antioxidant activities.

H (2) O (2)


Input: Arachidonate, docosahexaenoate, eicosapentaenoate and cholesterol levels were reduced in presence of H (2) O (2) and oxidized lipid products (isoprostanes, neuroprostanes 5 (S)-HETE, 20-HETE, 7-ketocholesterol, 27-hydroxycholesterol and resolvin D1) were rapidly released in the fish muscle.

Arachidonate

docosahexaenoate

eicosapentaenoate

cholesterol

H (2) O (2)

isoprostanes

neuroprostanes 5 (S)-HETE

resolvin D1


Input: This study validates oxidized lipid products, noticeably isoprostanes are measurable in marine fish muscle and should be considered when assessing oxidative stress especially due to exogenous factors.

isoprostanes


Input: Chemotherapy modulates the biological activity of breast cancer patients plasma: the protective properties of black chokeberry extract.


Input: In breast cancer patients (before and during anti-cancer therapy) oxidative/nitrative damage to various molecules is observed.


Input: Furthermore, anti-cancer treatments may also influence the hemostatic properties of blood platelets and plasma.


Input: The aim of our study was to assess the effect of oxidative/nitrative stress (estimated by measurements of the levels of carbonyl groups and 3-nitrotyrosine in proteins--ELISA and C-ELISA methods, respectively; lipid peroxidation and total antioxidant level--TAS) on the selected parameters of hemostatic activity of plasma (the process of fibrin polymerization and lysis) collected from breast cancer patients after surgery and after various phases of chemotherapy (doxorubicin and cyclophosphamide).

carbonyl

doxorubicin

cyclophosphamide


Input: Subsequently, we also evaluated the level of oxidative/nitrative stress and hemostatic activity in plasma from these patients in the presence of the commercial extract of Aronia melanocarpa (Aronox (R)) in vitro.


Input: Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy in Medical University of Lodz, Poland.


Input: We observed increased levels of biomarkers of oxidative/nitrative stress in plasma from patients with breast cancer (before or after surgery and after various phases of chemotherapy) in comparison to healthy group.


Input: Our further experiments demonstrated the hemostatic activity of plasma from the investigated patients differs from hemostatic properties of plasma obtained from healthy volunteers.


Input: We also recognize the existence of a relationship between oxidative stress (measured by the level of carbonyl groups) and changes of hemostasis in breast cancer patients after I and IV phases of chemotherapy.


Input: Moreover, the obtained results showed that the commercial extract from A. melanocarpa berries significantly reduced, in in vitro system, the oxidative/nitrative stress and hemostasis changes in plasma from breast cancer patients, after surgery and different phases of chemotherapy.


Input: Considering the data presented in this study, we suggest that the oxidative/nitrative stress in plasma obtained from breast cancer patients (not only before or after the surgery, but also after various phases of doxorubicin and cyclophosphamide chemotherapy) may induce changes of hemostatic activity, which may contribute to thrombosis in these patients.

doxorubicin

cyclophosphamide


Input: Our results also suggest that the commercial extract of A. melanocarpa may be regarded as a promising new source of bioactive antioxidant natural compounds for breast cancer patients.


Input: The AhR twist: ligand-dependent AhR signaling and pharmaco-toxicological implications.


Input: The aryl hydrocarbon receptor (AhR) is a transcription factor which is activated by diverse compounds and regulates the expression of xenobiotic metabolism genes.

aryl hydrocarbon


Input: Recent studies have unraveled unsuspected physiological roles and novel alternative ligand-specific pathways for this receptor.


Input: In this review, we discuss these novel aspects and focus on the different responses elicited by the diverse endogenous and/or exogenous AhR ligands.


Input: In addition to challenging the relevance of the' agonist/antagonist' classification of ligands, we introduce the concept of AhR plasticity as a primordial factor in the generation of these pathways.


Input: Finally, we suggest several promising perspectives for the pharmacological modulation of these responses.


Input: Optimization of 5-hydroxytryptamines as dual function inhibitors targeting phospholipase A2 and leukotriene A4 hydrolase.


Input: Dual function inhibitors targeting phospholipase A (2) (PLA (2)) and leukotriene A (4) hydrolase (LTA (4) H) may balance the arachidonic acid (AA) metabolic network and be used as new anti-inflammatory drugs.

arachidonic acid


Input: In previous study, we discovered multi-target drugs towards the AA metabolic network, among which a dual-target inhibitor (JMC08-4) for human nonpancreatic secretory phospholipase A (2) (hnps-PLA (2)) and human leukotriene A (4) hydrolase (LTA (4) H-h) was found.


Input: Based on the structure of compound JMC08-4, new dual-target inhibitors were designed assisted by molecular docking.


Input: In this report, a series of 5-hydroxytryptamine compounds were synthesized; and most of these title compounds showed more potent inhibitory activity than compound JMC08-4 in the in vitro bioassay against these two enzymes.


Input: The best one inhibited hnps-PLA (2) and LTA (4) H-h with IC (50) values of 9. 2 +/- 0. 5 mu M and 2. 4 +/- 1. 4 mu M, respectively.


Input: Design and synthesis of novel benzoheterocyclic derivatives as human acrosin inhibitors by scaffold hopping.

benzoheterocyclic


Input: Human acrosin is an attracting target for the development of novel male contraceptives.


Input: Scaffold hopping was used to optimize the isoxazolecarbaldehyde human acrosin inhibitors and extend their structure-activity relationships.

isoxazolecarbaldehyde


Input: Four kinds of scaffolds, namely benzimidazole, benzothiazole, 3H-indazole, and 5-phenyl-1H-pyrazole, were designed and synthesized.

benzimidazole

benzothiazole


Input: Most of the synthesized compounds showed potent human acrosin inhibitory activity and their binding modes were investigated by molecular docking.


Input: The scaffold of the compounds was found to be important for the inhibitory activity.


Input: Several compounds were more active than the positive control TLCK, suggesting that they can serve as good starting points for the discovery of novel male contraceptive agents.

TLCK


Input: Role of organic cation/carnitine transporter 1 in uptake of phenformin and inhibitory effect on complex I respiration in mitochondria.

carnitine

phenformin


Input: Phenformin causes lactic acidosis in clinical situations due to inhibition of mitochondrial respiratory chain complex I.

Phenformin


Input: It is reportedly taken up by hepatocytes and exhibits mitochondrial toxicity in the liver.


Input: In this study, uptake of phenformin and [(14) C] tetraethylammonium (TEA) and complex I inhibition by phenformin were examined in isolated liver and heart mitochondria.

phenformin

[(14) C] tetraethylammonium

TEA

phenformin


Input: Uptake of phenformin into isolated rat liver mitochondria was higher than that into heart mitochondria.

phenformin


Input: It was inhibited by several cat ionic compounds, which suggests the involvement of multispecific transport system (s).


Input: Similar characteristics were also observed for uptake of TEA; however, uptake of phenformin into mitochondria of organic cation/carnitine transporter 1 (OCTN1) knockout mice was lower than that in wild-type mice, whereas uptake of TEA was comparable between the two strains, suggesting the involvement of distinct transport mechanisms for these two cations in mitochondria.

TEA

phenformin

carnitine

TEA


Input: Inhibition by phenformin of oxygen consumption via complex I respiration in isolated rat liver mitochondria was greater than that in heart mitochondria, whereas inhibitory effect of phenformin on complex I respiration was similar in inside-out structured submitochondrial particles prepared from rat livers and hearts.

phenformin

oxygen

phenformin


Input: Lactic acidosis provoked by iv infusion of phenformin was weaker in octn1 (-/-) mice than that in wild-type mice.

phenformin


Input: These observations suggest that uptake of phenformin into liver mitochondria is at least partly mediated by OCTN1 and functionally relevant to its inhibition potential of complex I respiration.

phenformin


Input: This study was, thus, the first to demonstrate OCTN1-mediated mitochondrial transport and toxicity of biguanide in vivo in rodents.


Input: Novel Smad proteins localize to IR-induced double-strand breaks: interplay between TGF beta and ATM pathways.


Input: Cellular damage from ionizing radiation (IR) is in part due to DNA damage and reactive oxygen species, which activate DNA damage response (DDR) and cytokine signaling pathways, including the ataxia telangiectasia mutated (ATM) and transforming growth factor (TGF) beta/Smad pathways.

oxygen


Input: Using classic double-strand breaks (DSBs) markers, we studied the roles of Smad proteins in DDR and the crosstalk between TGF beta and ATM pathways.


Input: We observed co-localization of phospho-Smad2 (pSmad2) and Smad7 with DSB repair proteins following low and high linear energy transfer (LET) radiation in human fibroblasts and epithelial cells.

phospho


Input: The decays of both foci were similar to that of gamma H2AX foci.


Input: Irradiation with high LET particles induced pSmad2 and Smad7 foci tracks indicating the particle trajectory through cells.


Input: pSmad2 foci were absent in S phase cells, while Smad7 foci were present in all phases of cell cycle.


Input: pSmad2 (but not Smad7) foci were completely abolished when ATM was depleted or inactivated.


Input: In contrast, a TGF beta receptor 1 (TGF beta R1) inhibitor abrogated Smad7, but not pSmad2 foci at DSBs sites.


Input: In summary, we suggest that Smad2 and Smad7 contribute to IR-induced DSB signaling in an ATM or TGF beta R1-dependent manner, respectively.


Input: Removal of valproic acid by plasmapheresis in a patient treated for multiple sclerosis.

valproic acid


Input: We present a case of a patient with multiple sclerosis who was treated with plasmapheresis and valproic acid.

valproic acid


Input: We used therapeutic drug monitoring to determine whether plasma concentrations of valproic acid were kept within the therapeutic window and to determine the amount of valproic acid that was removed by plasmapheresis.

valproic acid

valproic acid


Input: Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma.


Input: Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations.


Input: However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition.


Input: These observations raise the intriguing possibility that, while loss of neurofibromin function is necessary for NF1-associated low-grade astrocytoma development, additional genetic changes may be required for full penetrance of the human brain tumor phenotype.


Input: To identify these potential cooperating genetic mutations, we performed whole-genome sequencing (WGS) analysis of three NF1-associated pilocytic astrocytoma (PA) tumors.


Input: We found that the mechanism of somatic NF1 loss was different in each tumor (frameshift mutation, loss of heterozygosity, and methylation).


Input: In addition, tumor purity analysis revealed that these tumors had a high proportion of stromal cells, such that only 50%-60% of cells in the tumor mass exhibited somatic NF1 loss.


Input: Importantly, we identified no additional recurrent pathogenic somatic mutations, supporting a model in which neuroglial progenitor cell NF1 loss is likely sufficient for PA formation in cooperation with a proper stromal environment.


Input: Increase of palmitic acid concentration impairs endothelial progenitor cell and bone marrow-derived progenitor cell bioavailability: role of the STAT5/PPAR gamma transcriptional complex.

palmitic acid


Input: Metabolic profiling of plasma nonesterified fatty acids discovered that palmitic acid (PA), a natural peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, is a reliable type 2 diabetes biomarker.

fatty acids

palmitic acid


Input: We investigated whether and how PA diabetic (d-PA) concentrations affected endothelial progenitor cell (EPC) and bone marrow-derived hematopoietic cell (BM-HC) biology.


Input: PA physiologic (n-PA) and d-PA concentrations were used.


Input: Proliferating cell nuclear antigen content and signal transducer and activator of transcription 5 (STAT5), PPAR gamma, cyclin D1, and p21 (Waf) expression were evaluated.


Input: Small interfering RNA technology, gene reporter luciferase assay, electrophoretic mobility shift assay, chromatin immunoprecipitation assay, and coimmunoprecipitation were exploited.


Input: In vivo studies and migration assays were also performed.


Input: d-PA, unlike n-PA or physiological and diabetic oleic and stearic acid concentrations, impaired EPC migration and EPC/BM-HC proliferation through a PPAR gamma-mediated STAT5 transcription inhibition.

oleic and stearic acid


Input: This event did not prevent the formation of a STAT5/PPAR gamma transcriptional complex but was crucial for gene targeting, as p21 (Waf) gene promoter, unlike cyclin D1, was the STAT5/PPAR gamma transcriptional target.


Input: Similar molecular events could be detected in EPCs isolated from type 2 diabetic patients.


Input: By expressing a constitutively activated STAT5 form, we demonstrated that STAT5 content is crucial for gene targeting and EPC fate.


Input: Finally, we also provide in vivo data that d-PA-mediated EPC dysfunction could be rescued by PPAR gamma blockade.


Input: These data provide first insights on how mechanistically d-PA drives EPC/BM-HC dysfunction in diabetes.


Input: The fidelity of transcription: RPB1 (RPO21) mutations that increase transcriptional slippage in S. cerevisiae.


Input: The fidelity of RNA synthesis depends on both accurate template-mediated nucleotide selection and proper maintenance of register between template and RNA.

nucleotide


Input: Loss of register, or transcriptional slippage, is particularly likely on homopolymeric runs in the template.


Input: Transcriptional slippage can alter the coding capacity of mRNAs and is used as a regulatory mechanism.


Input: Here we describe mutations in the largest subunit of Saccharomyces cerevisiae RNA polymerase II that substantially increase the level of transcriptional slippage.


Input: Alleles of RPB1 (RPO21) with elevated slippage rates were identified among 6-azauracil-sensitive mutants and were also isolated using a slippage-dependent reporter gene.


Input: Biochemical characterization of polymerase II isolated from these mutants confirms elevated levels of transcriptional slippage.


Input: The Effects of Carbohydrate, Unsaturated Fat, and Protein Intake on Measures of Insulin Sensitivity: Results from the OmniHeart Trial.

Carbohydrate


Input: OBJECTIVE Impaired insulin sensitivity increases the risk of cardiovascular disease.


Input: Although calorie restriction and weight loss increase insulin sensitivity, the effects of modifying macronutrient composition on insulin sensitivity are uncertain.


Input: The purpose of this study is to determine the effects on insulin sensitivity of a carbohydrate-rich diet (CARB; similar to the Dietary Approaches to Stop Hypertension [DASH] diet), a protein-rich diet (PROT; protein predominantly from plant sources), and an unsaturated fat-rich diet (UNSAT; predominantly monounsaturated).

carbohydrate

CARB


Input: RESEARCH DESIGN AND METHODS This study was a randomized, controlled, three-period, crossover feeding study.


Input: The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes.


Input: Diets were administered for 6 weeks each, with a washout period between diets of 2-4 weeks.


Input: Weight was held constant throughout the study.


Input: For our primary outcome, we calculated the quantitative insulin sensitivity check index (QUICKI) using the end-of-period fasting serum glucose and insulin.

glucose


Input: QUICKI is a validated measure of insulin sensitivity.


Input: The primary analyses used generalized estimating equations.


Input: RESULTS At baseline, mean (SD) BMI was 30. 2 (6. 1) kg/m (2), and mean (SD) QUICKI was 0. 35 (0. 04).


Input: The UNSAT diet increased QUICKI by 0. 005, more than the CARB diet (P = 0. 04).

CARB


Input: PROT had no significant effect compared with CARB.

CARB


Input: CONCLUSIONS A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease.

carbohydrate


Input: Given the well-recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity.


Input: Four-Year Change in Cardiorespiratory Fitness and Influence on Glycemic Control in Adults With Type 2 Diabetes in a Randomized Trial: The Look AHEAD Trial.


Input: OBJECTIVE To examine an intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) on 4-year change in fitness and physical activity (PA), and to examine the effect of change in fitness and PA, adjusting for potential confounders, on glycemic control in the Look AHEAD Trial.


Input: RESEARCH DESIGN AND METHODS Subjects were overweight/obese adults with type 2 diabetes mellitus (T2DM) with available fitness data at 4 years (n = 3, 942). This clinical trial randomized subjects to DSE or ILI.


Input: DSE subjects received standard care plus information related to diet, PA, and social support three times per year.


Input: ILI subjects received weekly intervention contact for 6 months, which was reduced over the 4-year period, and were prescribed diet and PA.


Input: Measures included weight, fitness, PA, and HbA1c.


Input: RESULTS The difference in percent fitness change between ILI and DSE at 4 years was significant after adjustment for baseline fitness and change in weight (3. 70 vs. 0. 94%; P < 0. 01).


Input: At 4 years, PA increased by 348 (1, 562) kcal/week in ILI vs. 105 (1, 309) kcal/week in DSE (P < 0. 01).


Input: Fitness change at 4 years was inversely related to change in HbA1c after adjustment for clinical site, treatment, baseline HbA1c, prescribed diabetes medication, baseline fitness, and weight change (P < 0. 01).


Input: Change in PA was not related to change in HbA1c.


Input: CONCLUSIONS A 4-year ILI increased fitness and PA in overweight/obese individuals with T2DM.


Input: Change in fitness was associated with improvements in glycemic control, which provides support for interventions to improve fitness in adults with T2DM.


Input: The chemical synthesis of DNA/RNA: our gift to science.


Input: It is a great privilege to contribute to the Reflections essays.


Input: In my particular case, this essay has allowed me to weave some of my major scientific contributions into a tapestry held together by what I have learned from three colleagues (Robert Letsinger, Gobind Khorana, and George Rathmann) who molded my career at every important junction.


Input: To these individuals, I remain eternally grateful, as they always led by example and showed many of us how to break new ground in both science and biotechnology.


Input: Relative to my scientific career, I have focused primarily on two related areas.


Input: The first is methodologies we developed for chemically synthesizing DNA and RNA.


Input: Synthetic DNA and RNA continue to be an essential research tool for biologists, biochemists, and molecular biologists.


Input: The second is developing new approaches for solving important biological problems using synthetic DNA, RNA, and their analogs.


Input: Quantum chemical study of the catalytic activation of methane by copper oxide and copper hydroxide cations.

methane

copper oxide

copper hydroxide


Input: The activation of methane and its subsequent conversion into more valuable feedstocks under ambient conditions are regarded as one of the major challenges in contemporary catalysis, due to its thermodynamically strong and kinetically inert C-H bond.

methane

C-H


Input: Several enzymes and synthetic bioinorganic systems perform the activation of C-H bonds in methane and small hydrocarbons, mediated by transition metal mononuclear centers.

C-H

methane

hydrocarbons

transition metal


Input: Among them, monocopper cores and, in particular, CuO (+) and CuOH (+) have been suggested as efficient catalytic centers; this activity has not been experimentally proven until very recently, mainly due to the difficulty to produce sufficient amounts of active species to demonstrate the bond activation processes.

CuO (+)

CuOH (+)


Input: The theoretical study presented here provides a thorough quantum chemical description of the activity of both species, together with molecular level insight into the elementary steps of the experimentally observed reactions.


Input: Post-HF (CCSD (T), CASPT2) and Density Functional Theory (DFT) methods have been used to unravel detailed electronic and mechanistic aspects of the reaction paths.


Input: Our study reveals the decisive role of the oxygen-centered radical in the reactivity of both species, and the improvement of the reactivity as a result of the protonation of the active species.

oxygen


Input: Patterned polymer nanowire arrays as an effective protein immobilizer for biosensing and HIV detection.


Input: We report an array of polymeric nanowires for effectively immobilizing biomolecules on biochips owing to the large surface area.


Input: The nanowires were fabricated in predesigned patterns using an inductively coupled plasma (ICP) etching process.


Input: Microfluidic biochips integrated using the substrates with arrays of nanowires and polydimethylsiloxane channels have been demonstrated to be effective for detecting antigens, and a detection limit of antigens at 0. 2 mu g mL (-1) has been achieved, which is improved by a factor of 50 compared to that based on flat substrates without the nanowires.

polydimethylsiloxane


Input: In addition, the high sensitivity for clinical detection of human immunodeficiency virus (HIV) antibody has also been demonstrated, showing a 20 times enhancement in fluorescent signal intensity between the samples with positive and negative HIV.


Input: Micro-mesoporous materials obtained by zeolite recrystallization: synthesis, characterization and catalytic applications.

zeolite


Input: The review covers the recent developments in the field of novel micro-mesoporous materials obtained by zeolite recrystallization.

zeolite


Input: The materials are classified into three distinctly different groups depending on the degree of recrystallization: (i) coated mesoporous zeolites (RZEO-1); (ii) micro-mesoporous nanocomposites (RZEO-2); and (iii) mesoporous materials with zeolitic fragments in the walls (RZEO-3).

zeolites


Input: The first part of the review is focused on the analysis of the synthetic strategies leading to different types of recrystallized materials.


Input: In the second part, a comprehensive view on their structure, texture and porosity in connection with acidic and diffusion properties is given.


Input: The last part is devoted to the catalytic applications of recrystallized materials.


Input: The advantages and disadvantages with respect to pure micro-and mesoporous molecular sieves and other hierarchical zeolites are critically analyzed and the future opportunities and perspectives are discussed.

zeolites


Input: Hydrophobic asymmetric ultrafiltration PVDF membranes: an alternative separator for VFB with excellent stability.

PVDF


Input: Polyvinylidene fluoride (PVDF) ultrafiltration membranes were investigated for the first time in vanadium redox flow battery (VFB) applications.

Polyvinylidene fluoride

PVDF

vanadium


Input: Surprisingly, PVDF ultrafiltration membranes with hydrophobic pore walls and relatively large pore sizes of several tens of nanometers proved able to separate vanadium ions and protons efficiently, thus being suitable as a VFB separator.

PVDF

vanadium


Input: The ion selectivity of this new type of VFB membrane could be tuned readily by controlling the membrane morphology via changes in the composition of the membrane casting solution, and the casting thickness.


Input: The results showed that the PVDF membranes offered good performances and excellent stability in VFB applications, where it could, performance-wise, truly substitute Nafion in VFB applications, but at a much lower cost.

PVDF

Nafion


Input: Lanthanide-doped luminescent nano-bioprobes: from fundamentals to biodetection.

Lanthanide


Input: Trivalent lanthanide (Ln (3 +))-doped luminescent inorganic nanoparticles (NPs), characterized by long-lived luminescence, large Stokes and/or anti-Stokes shifts, narrow emission bands and high photochemical stability, are considered to be promising candidates as luminescent bioprobes in biomedicine and biotechnology.

Trivalent lanthanide

Ln (3 +)


Input: In this feature article, we provide a brief overview of the most recent advances in Ln (3 +)-doped luminescent inorganic NPs as sensors, which covers from their chemical and physical fundamentals to biodetection, such as controlled synthesis methodology, surface modification chemistry, optical physics, and their promising applications in diverse bioassays, with an emphasis on heterogeneous and homogeneous in vitro biodetection.

Ln (3 +)


Input: Finally, some of the most important emerging trends and future efforts toward this active research field are also proposed.


Input: Biofunctionalized carbon nanotubes in neural regeneration: a mini-review.

carbon


Input: Carbon nanotubes (CNTs) have become an intriguing and promising biomaterial platform for the regeneration and functional recovery of damaged nerve tissues.

Carbon


Input: The unique electrical, structural and mechanical properties, diversity of available surface chemistry and cell-penetrating ability of CNTs have made them useful implantable matrices or carriers for the delivery of therapeutic molecules.


Input: Although there are still challenges being faced in the clinical applications of CNTs mainly due to their toxicity, many studies to overcome this issue have been published.


Input: Modification of CNTs with chemical groups to ensure their dissolution in aqueous media is one possible solution.


Input: Functionalization of CNTs with biologically relevant and effective molecules (biofunctionalization) is also a promising strategy to provide better biocompatibility and selectivity for neural regeneration.


Input: Here, we review recent advances in the use of CNTs to promote neural regeneration.


Input: Proteomic and metabolomic responses to connexin43 silencing in primary hepatocyte cultures.


Input: Freshly established cultures of primary hepatocytes progressively adopt a foetal-like phenotype and display increased production of connexin43.


Input: The latter is a multifaceted cellular entity with variable subcellular locations, including the mitochondrial compartment.


Input: Cx43 forms hemichannels and gap junctions that are involved in a plethora of physiological and pathological processes, such as apoptosis.


Input: The present study was conducted with the goal of shedding more light onto the role of connexin43 in primary hepatocyte cultures.


Input: Connexin43 expression was suppressed by means of RNA interference technology, and the overall outcome of this treatment on the hepatocellular proteome and metabolome was investigated using tandem mass tag-based differential protein profiling and (1) H NMR spectroscopy, respectively.

(1) H


Input: Global protein profiling revealed a number of targets of the connexin43 knock-down procedure, including mitochondrial proteins (heat shock protein 60, glucose-regulated protein 75, thiosulphate sulphurtransferase and adenosine triphosphate synthase) and detoxifying enzymes (glutathione S-transferase mu 2 and cytochrome P450 2C70).

glucose

thiosulphate

adenosine triphosphate

glutathione S


Input: At the metabolomic level, connexin43 silencing caused no overt changes, though there was some evidence for a subtle increase in intracellular glycine quantities.

glycine


Input: Collectively, these data could further substantiate the established existence of a mitochondrial connexin pool and could be reconciled with the previously reported involvement of connexin43 signalling in spontaneously occurring apoptosis in primary hepatocyte cultures.


Input: DFT and TDDFT study on the electronic structure and photoelectrochemical properties of dyes derived from cochineal and lac insects as photosensitizer for dye-sensitized solar cells.


Input: Essential parameters related to the photoelectrochemical properties, such as ground state geometries, electronic structures, oxidation potential and electron driving force, of cochineal insect dyes were investigated by DFT and TDDFT at the B3LYP/6-31 + G (d, p) level of the theory.


Input: The results show that the major charge flow dynamic for all dyes is the HOMO --> LUMO transition.


Input: The bi-coordinated binding mode, in which the dye uses one carboxyl-and hydroxyl oxygen bound to Ti (IV), is found for all dye-TiO (2) systems.

carboxyl-and hydroxyl oxygen

Ti (IV)

TiO (2)


Input: Additionally, the doubly bi-coordinated binding mode in which the dye used both carboxyl groups bound to two Ti (IV) is also possible due to high energy distribution occupied at anchoring groups.

carboxyl

Ti (IV)


Input: This study highlights that most of these insect dyes can be good photosensitizers in dye-sensitized solar cells based on their strong binding to the TiO (2) surface, good computed excited state oxidation potential and thermodynamically favored electron driving force.

TiO (2)


Input: Molecular vibrational spectroscopy characterization of epoxy graphene oxide from density functional calculations.

epoxy graphene oxide


Input: To further understand the structure of graphene oxide, several structures of graphene oxide were systematically investigated using density functional theory (DFT).

graphene oxide

graphene oxide


Input: Our models consisted of a hexagonal in-plane structure of graphene with epoxy groups, and different oxidation levels.

graphene

epoxy


Input: We found that different arrangements of these units yielded a range of vibrational spectra.


Input: Raman positions of the D and G bands depend sensitively on the local atomic configurations.


Input: Both structure energy and spectra computations indicate that the oxidation functional groups are energetically favorable to aggregate together and to be close to one another on the opposite side of graphene surface.

graphene


Input: Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis.


Input: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons.


Input: The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms.


Input: In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n = 17) of ALS patients diagnosed with quantitative electromyography.


Input: Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry.


Input: Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF.

manganese

aluminium

cadmium

cobalt

copper

zinc

vanadium

uranium


Input: We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e. g. inward directed transport.


Input: A pattern of multiple toxic metals is seen in ALS CSF.


Input: The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS.


Input: Ovariectomy Stimulates Hepatic Fat and Cholesterol Accumulation in High-fat Diet-fed Rats.

Cholesterol


Input: This study was designed to determine how estrogens withdrawal during a high-fat (HF) diet regimen affects liver triacylglycerol (TAG) and cholesterol accumulation.

estrogens

triacylglycerol

TAG

cholesterol


Input: Female Sprague-Dawley rats were submitted to a HF (42% energy as fat) or a standard (SD) diet for 6 weeks before being either ovariectomized (Ovx) or sham operated (Sham).


Input: Thereafter, Ovx and Sham rats were kept on the same diet for another 6 weeks leading to euthanasia.


Input: Liver TAG content was increased (p < 0. 01) in Ovx rats but not by the HF diet alone.

TAG


Input: However, the combination of HF diet and Ovx resulted in a greater liver TAG accumulation (p < 0. 06) than that observed in Ovx-SD/SD.

TAG


Input: Measurement of molecular markers of liver lipid metabolism revealed an increase in transcripts of markers of lipid oxidation (CPT-1 and PGC1; p < 0. 05) in rats fed the HF diet.


Input: This increase was, however, substantially less if HF fed rats were Ovx.


Input: Liver total cholesterol levels were increased (p < 0. 01) only in the Ovx-HF/HF rats while plasma cholesterol levels were increased in Ovx-SD/SD and in SHAM-HF/HF and Ovx-HF/HF rats.

cholesterol

cholesterol


Input: Transcripts of molecular markers of cholesterol metabolism suggest that biliary acids synthesis (CYP7a-1) was reduced in Ovx-SD/SD and Sham-HF/HF rats and even more so in Ovx-HF/HF rats.

cholesterol

biliary acids


Input: It is concluded that the effects of a HF diet on liver TAG accumulation are especially observed in Ovx rats possibly through a reduction in hepatic lipid oxidation.

TAG


Input: The combination of Ovx and HF diet also acts synergistically to favor liver cholesterol accumulation.

cholesterol


Input: In vitro antileishmanial activity of resveratrol originates from its cytotoxic potential against host cells.

resveratrol


Input: In addition to a range of beneficial pharmacological activities, resveratrol is recently reported to have potential antileishmanial activities in vitro.

resveratrol


Input: The present study was conducted to evaluate the effect of resveratrol on promastigotes and amastigotes of transgenic Leishmania major expressing green fluorescent protein in comparison with its direct cytotoxic effects on host cells (bone marrow-derived and J774-G8 macrophages, respectively).

resveratrol


Input: As assessed by FACS analysis, resveratrol showed moderate antipromastigote activity at < 35 micro g/mL (153. 2 micro M) and promising effects at higher sample concentrations.

resveratrol


Input: In contrast, the green fluorescent protein signal as a measure of the intracellular parasites' viability was reduced in a concentration-dependent manner.


Input: Resveratrol strongly inhibited NO production, but did not display direct NO-scavenging activity in sodium nitroprusside solution.

Resveratrol

NO

NO

sodium nitroprusside


Input: Western blotting indicated that resveratrol reduced recombinant interferon-gamma/LPS-induced expression of iNOS protein.

resveratrol


Input: Microscopic studies, MTT evaluation, and FACS analysis showed significant cytotoxic effects on host cells in a concentration-dependent manner.

MTT


Input: This finding suggests that the in vitro antileishmanial activity of resveratrol is due to cytotoxic effects on host cells rather than attributable to a specific antiparasitic potential.

resveratrol


Input: Cytotoxic cycloartane triterpenes of the traditional Chinese medicine " shengma " (Cimicifuga dahurica).

cycloartane triterpenes


Input: Twelve new 9, 19-cycloartane triterpenes (1-12), together with fourteen known compounds (13-26), were isolated from the roots of Cimicifuga dahurica.

9, 19-cycloartane triterpenes


Input: Their structures were determined by application of spectroscopic analyses and chemical methods.


Input: Biological evaluation of the compounds against human HL-60, SMMC-7721, A549, MCF-7, and SW-480 cell lines indicated that cimigenol-type glycosides (1-3, 19, and 20) showed broad-spectrum and moderate cytotoxicities, with IC50 values ranging from 4. 2 to 14. 5 micro M.

cimigenol


Input: Meanwhile, cimigenol-type aglycones (6-8, 15, 16, and 18) exhibited broad-spectrum and week cytotoxicities, having IC50 values around 20 micro M.

cimigenol


Input: In addition, the key points of the structure-activity relationships of aglycones with a cimigenol skeleton were discussed.

cimigenol


Input: Combined toxicity of polycyclic aromatic hydrocarbons and heavy metals to biochemical and antioxidant responses of free and immobilized Selenastrum capricornutum.

polycyclic aromatic hydrocarbons


Input: The aquatic environment often contains different groups of contaminants, but their combined toxicity on microalgae has seldom been reported.


Input: The present study compared the toxic effects of combined mixed polycyclic aromatic hydrocarbons (PAHs) and heavy metals on growth and antioxidant responses of free and immobilized microalga, Selenastrum capricornutum.

polycyclic aromatic hydrocarbons

PAHs


Input: Five PAHs-phenanthrene, fluorene, fluoranthene, pyrene, and benzo [a] pyrene-and four heavy metals at different concentrations-0. 05 to 0. 1 micro g Cd (2 +) ml (-1), 0. 05 to 1 micro g Cu (2 +) ml (-1), 0. 05 to 1 micro g Zn (2 +) ml (-1), and 0. 5 to 2. 5 micro g Ni (2 +) ml (-1)-were examined.

PAHs

phenanthrene

fluorene

fluoranthene

pyrene

benzo [a] pyrene

Cd (2 +)

Cu (2 +)

Zn (2 +)

Ni (2 +)


Input: Results showed that the chlorophyll a content of free and immobilized S. capricornutum was not affected by PAHs but was significantly inhibited by heavy metals.

chlorophyll a

PAHs


Input: Conversely, the antioxidant parameters, including the content of reduced glutathione (GSH) and the activities of superoxide dismutase and peroxidase, were significantly induced by both PAHs and metals.

glutathione

GSH

superoxide

PAHs


Input: For the combined toxic effects of PAHs and heavy metals, cell growth and antioxidant responses varied with exposure time and contaminants and differed between free and immobilized cells.

PAHs


Input: The effects of cocontaminants on the GSH content in free cells were mainly synergistic but changed to antagonistic in immobilized cells.

GSH


Input: The toxic effects of cocontamination on free cells were also more obvious than those on immobilized cells.


Input: These findings suggest that immobilization offers some protection to microalgal cells against toxic contaminants causing differences in the interaction and responses to combined toxicants between free and immobilized cells.


Input: Immobilized cells might be more suitable for treating wastewater containing toxic contaminants than free cells.


Input: Multifunctional uniform core-shell Fe3O4 @mSiO2 mesoporous nanoparticles for bimodal imaging and photothermal therapy.


Input: Multimodal imaging and simultaneous therapy is highly desirable because it can provide complementary information from each imaging modality for accurate diagnosis and, at the same time, afford an imaging-guided focused tumor therapy.


Input: In this study, indocyanine green (ICG), a near-infrared (NIR) imaging agent and perfect NIR light absorber for laser-mediated photothermal therapy, was successfully incorporated into superparamagnetic Fe (3) O (4) @mSiO (2) core-shell nanoparticles to combine the merit of NIR/magnetic resonance (MR) bimodal imaging properties with NIR photothermal therapy.

indocyanine green

ICG

Fe (3) O (4)


Input: The resultant nanoparticles were homogenously coated with poly (allylamine hydrochloride) (PAH) to make the surface of the composite nanoparticles positively charged, which would enhance cellular uptake driven by electrostatic interactions between the positive surface of the nanoparticles and the negative surface of the cancer cell.

poly (allylamine hydrochloride)

PAH


Input: A high biocompatibility of the achieved nanoparticles was demonstrated by using a cell cytotoxicity assay.


Input: Moreover, confocal laser scanning microscopy (CLSM) observations indicated excellent NIR fluorescent imaging properties of the ICG-loaded nanoparticles.

ICG


Input: The relatively high r (2) value (171. 6 mM (-1) s (-1)) of the nanoparticles implies its excellent capability as a contrast agent for MRI.


Input: More importantly, the ICG-loaded nanoparticles showed perfect NIR photothermal therapy properties, thus indicating their potential for simultaneous cancer diagnosis as highly effective NIR/MR bimodal imaging probes and for NIR photothermal therapy of cancerous cells.

ICG


Input: Non-ionic dendronized multiamphiphilic polymers as nanocarriers for biomedical applications.


Input: A new class of non-ionic dendronized multiamphiphilic polymers is prepared from a biodegradable (AB) n-type diblock polymer synthesized from 2-azido-1, 3-propanediol (azido glycerol) and polyethylene glycol (PEG)-600 diethylester using Novozym-435 (Candida antarctica lipase) as a biocatalyst, following a well-established biocatalytic route.

2-azido-1, 3-propanediol

azido glycerol

polyethylene glycol

PEG

diethylester


Input: These polymers are functionalized with dendritic polyglycerols (G1 and G2) and octadecyl chains in different functionalization levels via click chemistry to generate dendronized multiamphiphilic polymers.

polyglycerols

octadecyl


Input: Surface tension measurements and dynamic light scattering studies reveal that all of the multiamphiphilic polymers spontaneously self-assemble in aqueous solution.


Input: Cryogenic transmission electron microscopy further proves the formation of multiamphiphiles towards monodisperse spherical micelles of about 7-9 nm in diameter.


Input: The evidence from UV-vis and fluorescence spectroscopy suggests the effective solubilization of hydrophobic guests like pyrene and 1-anilinonaphthalene-8-sulfonic acid within the hydrophobic core of the micelles.

pyrene

1-anilinonaphthalene-8-sulfonic acid


Input: These results demonstrate the potential of these dendronized multiamphiphilic polymers for the development of prospective drug delivery systems for the solubilization of poorly water soluble drugs.


Input: Enhanced nonenzymatic ligation of homopurine miniduplexes: support for greater base stacking in a pre-RNA world.


Input: The ancestors of RNA?


Input: There is a long-standing proposal that contemporary nucleic acids might have evolved from RNA-like polymers that utilized only purine-purine base pairs.

nucleic acids

purine

purine


Input: Here we demonstrate the great advantage that increased nucleobase stacking area provides for nonenzymatic ligation.


Input: Preparation of functional water-soluble low-cytotoxic poly (methacrylate) s with pendant cationic L-lysines for efficient gene delivery.

poly (methacrylate) s

L-lysines


Input: In this work, we present the preparation of water-soluble poly (methacrylate) s with pendant cationic L-lysines PHMLs (6-30 K).

poly (methacrylate) s

L-lysines


Input: Plasmid DNA binding affinity as well as particle sizes and zeta potentials of the polyplexes were examined for these PHML vectors, and their cytotoxicities were assayed with HeLa cells by CCK-8 and lactate dehydrogenase kits.


Input: Gene transfection efficacy and intracellular uptake of the polyplexes by the PHML vectors were also studied with HeLa cells.


Input: As a result, it was revealed that the low cytotoxic PHMLs tended to exhibit gene transfection efficiencies significantly higher than those of the linear structural PLL (15-30 K) control, in particular the molecular weight of a PHML vector remarkably influenced its pDNA binding affinity, transfection efficacy and intracellular uptake of the polyplexes.


Input: Biocompatible fibrous networks of cellulose nanofibres and collagen crosslinked using genipin: potential as artificial ligament/tendons.

genipin


Input: Bio-based fibrous nanocomposites of cellulose nanofibres and non-crosslinked/crosslinked collagen were prepared by in situ pH-induced fibrillation of collagen phase and sterilized using gamma rays at 25 KGy.


Input: Collagen phase is crosslinked using genipin, a bio-based crosslinker that introduces flexible crosslinks.

genipin


Input: Microscopy studies of the prepared materials showed nanostructured fibrous collagen and cellulose dispersed in collagen matrix.


Input: Mechanical performance of the sterilized nanocomposites was close to that of natural ligament and tendon, in simulated body conditions.


Input: Cytocompatibility studies indicated that these nanocomposites allowed human ligament cell and human endothelial cell adhesion, growth, and differentiation; which is eminently favourable to ligament tissue engineering.


Input: N-cyano sulfoximines: COX inhibition, anticancer activity, cellular toxicity, and mutagenicity.

N-cyano sulfoximines


Input: From insects to cancer: N-Cyano sulfoximines were evaluated for COX inhibition and antiproliferative activity against a panel of cancer cell lines.

N-Cyano sulfoximines


Input: The most active compound exhibited potent COX-2 inhibition, some selectivity for COX-2 over COX-1, only slight cytotoxicity towards healthy cells (HaCaT skin cells), and no mutagenic potential (as determined by an Ames assay).


Input: Central nervous system disposition and metabolism of Fosdevirine (GSK2248761), a non-nucleoside reverse transcriptase inhibitor: an LC-MS and Matrix-assisted laser desorption/ionization imaging MS investigation into central nervous system toxicity.

Fosdevirine

nucleoside


Input: The CNS disposition and metabolism of Fosdevirine (FDV), an HIV non-nucleoside reverse transcriptase inhibitor, was investigated in four patients who unexpectedly experienced seizures after at least 4 weeks of treatment in a Phase IIb, HIV-1 treatment experienced study.

Fosdevirine

FDV

nucleoside


Input: In addition, the CNS disposition and metabolism of FDV was examined in samples from rabbit, minipig, and monkey studies.

FDV


Input: LC-MS was used to characterize and estimate the concentrations of FDV and its metabolites in cerebral spinal fluid (seizure patients, rabbit, and monkey) and brain homogenate (rabbit, minipig, and monkey).

FDV


Input: The application of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) provided the spatial distribution of FDV and its metabolites in brain tissue (rabbit, minipig, and monkey).

FDV


Input: A cysteine conjugate metabolite resulting from an initial glutathione (GSH) Michael addition to the trans-phenyl acrylonitrile moiety of FDV was the predominant drug-related component in the samples from seizure patients, rabbits, and minipigs.

cysteine

glutathione

GSH

trans-phenyl acrylonitrile

FDV


Input: This metabolite persisted in the CNS for an extended period of time after the last dose in both seizure patients and minipigs.


Input: Furthermore, the localization of this metabolite was found to be highly associated with the white matter in rabbit and minipig brain sections by MALDI IMS.


Input: In contrast, the predominant component in monkey CNS was FDV, which was shown to be highly associated with the gray matter.

FDV


Input: On the basis of these data, several hypothesizes are considered, which might provide insights into species differences in CNS toxicity/seizures observed after FDV dosing.

FDV


Input: Epitope-guided engineering of monobody binders for in vivo inhibition of Erk-2 signaling.


Input: Although the affinity optimization of protein binders is straightforward, engineering epitope specificity is more challenging.


Input: Targeting a specific surface patch is important because the biological relevance of protein binders depends on how they interact with the target.


Input: They are particularly useful to test hypotheses motivated by biochemical and structural studies.


Input: We used yeast display to engineer monobodies that bind a defined surface patch on the mitogen activated protein kinase (MAPK) Erk-2.


Input: The targeted area (" CD " domain) is known to control the specificity and catalytic efficiency of phosphorylation by the kinase by binding a linear peptide (" D " peptide) on substrates and regulators.


Input: An inhibitor of the interaction should thus be useful for regulating Erk-2 signaling in vivo.


Input: Although the CD domain constitutes only a small percentage of the surface area of the enzyme (~ 5%), sorting a yeast displayed monobody library with wild type (wt) Erk-2 and a rationally designed mutant led to isolation of high affinity clones with desired epitope specificity.


Input: The engineered binders inhibited the activity of Erk-2 in vitro and in mammalian cells.


Input: Furthermore, they specifically inhibited the activity of Erk-2 orthologs in yeast and suppressed a mutant phenotype in round worms caused by overactive MAPK signaling.


Input: The study therefore shows that positive and negative screening can be used to bias the evolution of epitope specificity and predictably design inhibitors of biologically relevant protein-protein interaction.


Input: Controllable electrical properties of metal-doped In2O3 nanowires for high-performance enhancement-mode transistors.


Input: In recent years, In (2) O (3) nanowires (NWs) have been widely explored in many technological areas due to their excellent electrical and optical properties; however, most of these devices are based on In (2) O (3) NW field-effect transistors (FETs) operating in the depletion mode, which induces relatively higher power consumption and fancier circuit integration design.

In (2) O (3)

In (2) O (3)


Input: Here, n-type enhancement-mode In (2) O (3) NW FETs are successfully fabricated by doping different metal elements (Mg, Al, and Ga) in the NW channels.

In (2) O (3)

Mg

Al

Ga


Input: Importantly, the resulting threshold voltage can be effectively modulated through varying the metal (Mg, Ga, and Al) content in the NWs.

Mg

Ga

Al


Input: A series of scaling effects in the mobility, transconductance, threshold voltage, and source-drain current with respect to the device channel length are also observed.


Input: Specifically, a small gate delay time (0. 01 ns) and high on-current density (0. 9 mA/mu m) are obtained at 300 nm channel length.


Input: Furthermore, Mg-doped In (2) O (3) NWs are then employed to fabricate NW parallel array FETs with a high saturation current (0. 5 mA), on/off ratio (> 10 (9)), and field-effect mobility (110 cm (2)/V. s), while the subthreshold slope and threshold voltage do not show any significant changes.

Mg

In (2) O (3)


Input: All of these results indicate the great potency for metal-doped In (2) O (3) NWs used in the low-power, high-performance thin-film transistors.

In (2) O (3)


Input: Drug safety evaluation of defibrotide.


Input: INTRODUCTION: Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT).


Input: Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD).


Input: None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions.


Input: AREAS COVERED: This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases.


Input: The literature review was conducted using a PubMed search with the fixed term' defibrotide' in combination with >= 1 of' safety',' veno-occlusive disease' (with and without' treatment',' prevention'),' oncology',' myeloma',' microangiopathy',' anti-thrombotic' and' peripheral vascular disorder'.


Input: Related articles from the EBMT and ASH conference websites were also included.


Input: EXPERT OPINION: DF was well tolerated in majority of the studies.


Input: The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.


Input: A new antibacterial phenanthrenequinone from Dendrobium sinense.

phenanthrenequinone


Input: A new phenanthrenequinone, named denbinobin B (1), together with three known phenanthrenes was isolated from the whole plant of Dendrobium sinense T.

phenanthrenequinone

denbinobin B

phenanthrenes


Input: Tang et F. T.


Input: Wang, an endemic and endangered orchid to Hainan Island.


Input: The new compound was elucidated using a combination of 1D, 2D NMR (COSY, HMQC, and HMBC) techniques, and HR-ESI-MS analyses.


Input: Compound 1 exhibited moderate antibacterial activity against Staphylococcus aureus with the diameter of the inhibition zone of 16. 5 mm.


Input: From a cytotoxic agent to the discovery of a novel antimalarial agent.


Input: A novel cytotoxin 3, 5-bis (4-chlorobenzylidene)-1-[4-{2-(4-morpholinyl) ethoxy} phenyl-carbonyl]-4-piperidone hydrochloride 2 demonstrated potent antimalarial properties with IC (50) values of 0. 60 and 1. 97 mu M against the drug sensitive D6 strain and the C235 drug-resistant strain of Plasmodium falciparum.

3, 5-bis (4-chlorobenzylidene)-1-[4-{2-(4-morpholinyl) ethoxy} phenyl-carbonyl]-4-piperidone hydrochloride


Input: This compound concentrates in red blood cells, lowers glutathione concentrations in erythrocytes and permeates across CACO-2 cells.

glutathione


Input: These data reveal 2 to be a promising lead compound in the quest for novel antimalarial agents.


Input: Facile regioselective synthesis of novel bioactive thiazolyl-pyrazoline derivatives via a three-component reaction and their antimicrobial activity.

thiazolyl-pyrazoline


Input: A series of novel 2-(3, 5-diphenyl-4, 5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles have been prepared by a three-component cyclo-condensation of various chalcones, thiosemicarbazide and phenacyl bromide.

2-(3, 5-diphenyl-4, 5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles

chalcones

thiosemicarbazide

phenacyl bromide


Input: The easy work-up of the products, rapid reaction, and mild conditions are notable features of this protocol.


Input: The reaction was efficiently catalyzed in one-pot by a few drops of HCl in EtOH under reflux conditions providing the title compounds in moderate to high yields.

HCl

EtOH


Input: The antibacterial activity of the selected products was examined.


Input: Some products exhibit promising activities.


Input: Cyprodinil as an activator of aryl hydrocarbon receptor.

Cyprodinil

aryl hydrocarbon


Input: Cyprodinil is a pyrimidinamine fungicide, used worldwide by agriculture.

Cyprodinil

pyrimidinamine


Input: It is used to protect fruit plants and vegetables from a wide range of pathogens.


Input: Benzo [a] pyrene (BaP) and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) are toxic environmental pollutants and are prototypes of aryl hydrocarbon receptor (AHR) ligands.

Benzo [a] pyrene

BaP

2, 3, 7, 8-tetrachlorodibenzo-p-dioxin

TCDD

aryl hydrocarbon


Input: Although the structure of cyprodinil distinctly differs from those of BaP and TCDD, our results show that cyprodinil induced nuclear translocation of the AHR, and induced the transcriptional activity of aryl hydrocarbon response element (AHRE).

cyprodinil

BaP

TCDD

cyprodinil

aryl hydrocarbon


Input: Cyprodinil induced the expression of cytochrome P450 (CYP) 1A1, a well-known AHR-targeted gene, in ovarian granulosa cells, HO23, and hepatoma cells, Hepa-1c1c7.

Cyprodinil


Input: Its induction did not appear in AHR signal-deficient cells, and was blocked by the AHR antagonist, CH-223191.


Input: Cyprodinil decreased AHR expression in HO23 cells, resulting in CYP1A1 expression decreasing after it peaked at 9h of treatment in HO23 cells.

Cyprodinil


Input: Dexamethasone is a synthetic agonist of glucocorticoids.

Dexamethasone


Input: Cyprodinil enhanced dexamethasone-induced gene expression, and conversely, its induction of CYP1A1 expression was decreased by dexamethasone in HO23 cells, indicating its induction of crosstalk between the AHR and glucocorticoid receptor and its role as a potential endocrine disrupter.

Cyprodinil

dexamethasone

dexamethasone


Input: In addition to BaP, TCDD, and an AHR agonist, beta-NF, cyprodinil also phosphorylated extracellular signal-regulated kinase (ERK) in HO23 and Hepa-1c1c7 cells, indicating its deregulation of ERK activity.

BaP

TCDD

cyprodinil


Input: In summary, our results demonstrate that cyprodinil, similar to BaP, acts as an AHR activator, a potential endocrine disrupter, and an ERK disrupter.

cyprodinil

BaP


Input: Metformin-mediated downregulation of p38 mitogen-activated protein kinase-dependent excision repair cross-complementing 1 decreases DNA repair capacity and sensitizes human lung cancer cells to paclitaxel.

Metformin

paclitaxel


Input: Metformin, an extensively used and well-tolerated drug for treating individuals with type 2 diabetes, has recently gained significant attention as an anticancer drug.

Metformin


Input: On the other hand, paclitaxel (Taxol) is a new antineoplastic drug that has shown promise in the treatment of non-small cell lung cancer (NSCLC).

paclitaxel

Taxol


Input: High expression levels of excision repair cross-complementary 1 (ERCC1) in cancers have been positively associated with the DNA repair capacity and a poor prognosis in NSCLC patients treated with platinum-containing chemotherapy.

platinum


Input: In this current study, paclitaxel was found to increase phosphorylation of mitogen-activated protein kinase (MAPK) kinase 3/6 (MKK3/6)-p38 MAPK as well as protein and mRNA levels of ERCC1 in H1650 and H1703 cells.

paclitaxel


Input: Moreover, paclitaxel-induced ERCC1 protein and mRNA levels significantly decreased via the downregulation of p38 activity by either a p38 MAPK inhibitor SB202190 or p38 knockdown with specific small interfering RNA (siRNA).

paclitaxel


Input: Specific inhibition of ERCC1 with siRNA was found to enhance the paclitaxel-induced cytotoxic effect and growth inhibition.

paclitaxel


Input: Furthermore, metformin was able to not only decrease the paclitaxel-induced p38 MAPK-mediated ERCC1 expression, but also augment the cytotoxic effect induced by paclitaxel.

metformin

paclitaxel

paclitaxel


Input: Finally, expression of constitutive activate MKK6 or HA-p38 MAPK vectors in lung cancer cells was able to abrogate ERCC1 downregulation by metformin and paclitaxel as well as cell viability and DNA repair capacity.

metformin

paclitaxel


Input: Overall, our results suggest that inhibition of the p38 MAPK signaling by metformin coupled with paclitaxel therapy in human NSCLC cells may be a clinically useful combination, which however will require further validation.

metformin

paclitaxel


Input: Carboxylesterase-2 is a highly sensitive target of the antiobesity agent orlistat with profound implications in the activation of anticancer prodrugs.

orlistat


Input: Orlistat has been the most used anti-obesity drug and the mechanism of its action is to reduce lipid absorption by inhibiting gastrointestinal lipases.

Orlistat


Input: These enzymes, like carboxylesterases (CESs), structurally belong to the alpha/beta hydrolase fold superfamily.


Input: Lipases and CESs are functionally related as well.


Input: Some CESs (e. g., human CES1) have been shown to hydrolyze lipids.


Input: This study was designed to test the hypothesis that orlistat inhibits CESs with higher potency toward CES1 than CES2, a carboxylesterase with little lipase activity.

orlistat


Input: Liver microsomes and recombinant CESs were tested for the inhibition of the hydrolysis of standard substrates and the anticancer prodrugs pentyl carbamate of p-aminobenzyl carbamate of doxazolidine (PPD) and irinotecan.

pentyl carbamate

p-aminobenzyl carbamate

doxazolidine

PPD

irinotecan


Input: Contrary to the hypothesis, orlistat at 1 nM inhibited CES2 activity by 75% but no inhibition on CES1, placing CES2 one of the most sensitive targets of orlistat.

orlistat


Input: The inhibition varied among some CES2 polymorphic variants.


Input: Pretreatment with orlistat reduced the cell killing activity of PPD.

orlistat

PPD


Input: Certain mouse but not rat CESs were also highly sensitive.


Input: CES2 is responsible for the hydrolysis of many common drugs and abundantly expressed in the gastrointestinal track and liver.


Input: Inhibition of this carboxylesterase probably presents a major source for altered therapeutic activity of these medicines if co-administered with orlistat.

orlistat


Input: In addition, orlistat has been linked to various types of organ toxicities, and this study provides an alternative target potentially involved in these toxicological responses.

orlistat


Input: Microwave synthesis, characterization and bio-efficacy evaluation of novel chalcone based 6-carbethoxy-2-cyclohexen-1-one and 2H-indazol-3-ol derivatives.

chalcone


Input: Novel chalcone based 6-carbethoxy-2-cyclohexen-1-one and 2H-indazol-3-ol derivatives were synthesized and characterized by using spectral techniques like IR, (1) H NMR, (13) C NMR, COSY, DEPT, and GC-MS.

chalcone

(1) H

(13) C


Input: All these compounds were screened for anti-fungal, anti-bacterial and anti-oxidant activity.


Input: Cyclohexenone derivatives, in general, showed better anti-fungal and anti-bacterial activity than parent chalcones.

Cyclohexenone

chalcones


Input: Whereas, all the Indazole derivatives showed very good anti-oxidant activity and some were also found to be active as anti-bacterial agent.

Indazole


Input: Among the screened compounds, 15 was found to be most active as anti-fungal agent (against Rhizoctonia solani, LC (50) = 2. 36 mu g mL (-1)), 15b was found to be most active anti-bacterial agent (against Klebsiella pneumonia, MIC = 24. 68 mu g mL (-1)) and 14b emerged as most active anti-oxidant (IC (50) = 19. 81 mu g mL (-1)).


Input: Aryl hydrocarbon receptor is a target of 17-Allylamino-17-demethoxygeldanamycin and enhances its anticancer activity in lung adenocarcinoma cells.

Aryl hydrocarbon


Input: We have demonstrated that aryl hydrocarbon receptor (AhR) is overexpressed in lung adenocarcinoma (AD).

aryl hydrocarbon


Input: AhR is usually associated with heat shock protein 90 (Hsp90) in the cytoplasm.


Input: 17-Allylamino-17-demethoxygeldanamycin (17-AAG), an Hsp90 inhibitor, is currently under evaluation for its anticancer activity in clinical trials.


Input: Here we investigated whether AhR plays a role in 17-AAG-mediated anticancer activity by functioning as a downstream target or by modulating its anticancer efficacy.


Input: AhR expression in lung AD cells was modulated by siRNA interference or overexpression.


Input: Tumor growth was determined with colony formation in vitro or in vivo.


Input: Anticancer activity of 17-AAG was determined by measuring cell viability, cell cycle distribution, and expression of cell cycle regulators.


Input: Proteins and mRNA levels were examined by immunoblotting and the real-time reverse transcription-polymerase chain reaction, respectively.


Input: In this study, AhR overexpression positively modulated growth of lung AD cells, at least partially, via RelA-dependent mechanisms.


Input: Although treatment with 17-AAG reduced AhR levels and AhR-regulated gene expression in lung AD cells, AhR expression increased anticancer activity of 17-AAG.


Input: In addition, 17-AAG treatment reduced cell viability, CDK2, CDK4, cyclin E, cyclin D1, and phosphorylated Rb levels in AhR-expressing lung AD cells.


Input: NAD (P) H: quinone oxidoreductase (NQO1), which is regulated by AhR, was shown to increase anticancer activity of 17-AAG in cells.

NAD (P) H

quinone


Input: Knockdown of NQO1 expression attenuated the reduction of cell cycle regulators by 17-AAG treatment in AhR overexpressed cells.


Input: We demonstrated that AhR protein not only functions as a downstream target of 17-AAG, but also enhances anticancer activity of 17-AAG in lung AD cells.


Input: Surgical trauma induces iron accumulation and oxidative stress in a rodent model of postoperative cognitive dysfunction.


Input: Postoperative cognitive dysfunction (POCD) is recognized as a complication after surgery in the elderly.


Input: The exact pathogenic mechanisms of POCD are still unknown.


Input: In this study, we investigated the role of iron accumulation within the central nervous system in the development of cognitive dysfunction in rats following splenectomy.

iron


Input: Cognitive function was assessed using a Morris water maze on postoperative days 1, 3, and 7.


Input: Impaired cognitive function was observed on days 1 and 3 after splenectomy, while an anesthesia-alone group showed no significant difference from the control.


Input: Serum iron levels decreased and brain iron content increased on days 1 and 3 after surgery, which was in parallel with the impairment of cognitive function.


Input: Furthermore, the levels of proteins involved in the maintenance of brain iron homeostasis, including ferritin, transferrin receptor 1, and iron regulatory protein 2, were significantly different at postoperative days 1 and 3 in the hippocampus of splenectomized animals when compared with those of the control.

iron

iron


Input: The alterations in iron homeostasis were accompanied by intensified oxidative stress as measured by increases in the lipid peroxidation product, malondialdehyde, and a decrease in the levels of superoxide dismutase activity.

iron

malondialdehyde

superoxide


Input: Overall, these findings suggest that the impaired cognitive function was primarily due to surgical trauma rather than anesthesia.


Input: Increased iron accumulation and oxidative stress in the brain, especially in the hippocampus, may be involved in the pathogenesis of POCD.


Input: Pharmacogenomics of gemcitabine metabolism: functional analysis of genetic variants in cytidine deaminase and deoxycytidine kinase.

gemcitabine

cytidine

deoxycytidine


Input: Gemcitabine (dFdC, 2', 2'-difluorodeoxycytidine) is metabolized by cytidine deaminase (CDA) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.

Gemcitabine

dFdC

2', 2'-difluorodeoxycytidine

cytidine

deoxycytidine


Input: Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite 2', 2'-difluorodeoxyuridine (dFdU) as substrates.

cytarabine

Ara-C

dFdC

2', 2'-difluorodeoxyuridine

dFdU


Input: All three CDA proteins showed similar K (m) and V (max) for Ara-C and dFdC deamination, except for CDA70Thr, which had a 2. 5-fold lower K (m) and 6-fold lower V (max) for Ara-C deamination.

Ara-C

dFdC

Ara-C


Input: All four DCK proteins yielded comparable metabolic activity for Ara-C and dFdC monophosphorylation, except for DCK24Val, which demonstrated an approximately 2-fold increase (P < 0. 05) in the intrinsic clearance of dFdC monophosphorylation due to a 40% decrease in K (m) (P < 0. 05).

Ara-C

dFdC

dFdC


Input: DCK did not significantly contribute to dFdU monophosphorylation.

dFdU


Input: In conclusion, the Lys27Gln substitution does not significantly modulate CDA activity toward dFdC, and therefore would not contribute to interindividual variability in response to gemcitabine.

dFdC

gemcitabine


Input: The higher in vitro catalytic efficiency of DCK24Val toward dFdC monophosphorylation may be relevant to dFdC clinical response.

dFdC

dFdC


Input: The substrate-dependent alterations in activities of CDA70Thr and DCK24Val in vitro were observed for the first time, and demonstrate that the in vivo consequences of these genetic variations should not be extrapolated from one substrate of these enzymes to another.


Input: Stress granules inhibit apoptosis by reducing reactive oxygen species production.

oxygen


Input: Cells can undergo two alternative fates following exposure to environmental stress: they either induce apoptosis or inhibit apoptosis and then repair the stress-induced alterations.


Input: These processes minimize cell loss and prevent the survival of cells with aberrant DNA and protein alterations.


Input: These two alternative fates are partly controlled by stress granules (SGs).


Input: While arsenite, hypoxia, and heat shock induce the formation of SGs that inhibit apoptosis, X-ray irradiation and genotoxic drugs do not induce SGs, and they are more prone to trigger apoptosis.

arsenite


Input: However, it is unclear precisely how SGs control apoptosis.


Input: This study found that SGs suppress the elevation of reactive oxygen species (ROS), and this suppression is essential for inhibiting ROS-dependent apoptosis.

oxygen


Input: This antioxidant activity of SGs is controlled by two SG components, GTPase-activating protein SH3 domain binding protein 1 (G3BP1) and ubiquitin-specific protease 10 (USP10).


Input: G3BP1 elevates the steady-state ROS level by inhibiting the antioxidant activity of USP10.


Input: However, following exposure to arsenite, G3BP1 and USP10 induce the formation of SGs, which uncovers the antioxidant activity of USP10.

arsenite


Input: We also found that the antioxidant activity of USP10 requires the protein kinase activity of ataxia telangiectasia mutated (ATM).


Input: This work reveals that SGs are critical redox regulators that control cell fate under stress conditions.


Input: Increased oxidized low-density lipoprotein causes blood-brain barrier disruption in early-onset preeclampsia through LOX-1.


Input: Early-onset preeclampsia (EPE) is a severe form of preeclampsia that involves life-threatening neurological complications.


Input: However, the underlying mechanism by which EPE affects the maternal brain is not known.


Input: We hypothesized that plasma from women with EPE increases blood-brain barrier (BBB) permeability vs. plasma from women with late-onset preeclampsia (LPE) or normal pregnancy (NP) and investigated its underlying mechanism by perfusing cerebral veins from nonpregnant rats (n = 6-7/group) with human plasma from women with EPE, LPE, or NP and measuring permeability.


Input: We show that plasma from women with EPE significantly increased BBB permeability vs. plasma from women with LPE or NP (P < 0. 001).


Input: BBB disruption in response to EPE plasma was due to a 260% increase of circulating oxidized LDL (oxLDL) binding to its receptor, LOX-1, and subsequent generation of peroxynitrite (P < 0. 001).

peroxynitrite


Input: A rat model with pathologically high lipid levels in pregnancy showed symptoms of preeclampsia, including elevated blood pressure, growth-restricted fetuses, and LOX-1-dependent BBB disruption, similar to EPE (P < 0. 05).


Input: Thus, we have identified LOX-1 activation by oxLDL and subsequent peroxynitrite generation as a novel mechanism by which disruption of the BBB occurs in EPE.

peroxynitrite


Input: As increased BBB permeability is a primary means by which seizure and other neurological symptoms ensue, our findings highlight oxLDL, LOX-1, and peroxynitrite as important therapeutic targets in EPE.

peroxynitrite


Input: Embryonic stem cell-based screen for small molecules: cluster analysis reveals four response patterns in developing neural cells.


Input: Neural differentiation of embryonic stem cells (ESC) is considered a promising model to perform in vitro testing for neuroactive and neurotoxic compounds.


Input: We studied the potential of a dual reporter murine ESC line to identify bioactive and/or toxic compounds.