Input: Oral intubation with CA or RA alone for five days was conducted prior to treatment with a single dose of tert-butyl hydroperoxide (0. 5mmol/kg b. w., i. p.), which led to a significant reduction of indicators of hepatic toxicity, such as aspartate aminotransferase, alanine aminotransferase, oxidized glutathione, lipid peroxidation and enzyme activities related to antioxidant such as catalase, glutathione peroxidase and superoxide dismutase.

tert-butyl hydroperoxide

aspartate

alanine

oxidized glutathione

glutathione

superoxide


Input: Interestingly, compared to treatment with CA or RA alone, a combination of both compounds more increased the endogenous antioxidant enzymes and glutathione (GSH) and decreased lipid peroxidation in livers.

glutathione


Input: These results suggest that CA from perilla leaves plays a role in the increased hepatic GSH concentration, and shows an additive hepatic protection with RA against oxidative hepatic damage.

GSH


Input: Effects of silicon on osteoblast activity and bone mineralization of MC3T3-E1 cells.

silicon


Input: Previous studies have reported that dietary silicon (Si) intake is positively associated with bone health including bone mineral density.

silicon

Si


Input: Although the amount of Si intake is high among trace elements in humans, how dietary Si affects bone formation at the cellular level is not well addressed.

Si

Si


Input: The purpose of this study was to investigate the role of Si in osteoblast activity and bone mineralization.

Si


Input: MC3T3-E1 was cultured as mature osteoblasts and treated with sodium metasilicate (0, 1, 5, 10, 25, 50, and 100 mu M) as a source of Si.

sodium metasilicate

Si


Input: After 7 days of treatment, 5 and 10 mu M of sodium metasilicate significantly increased intracellular alkaline phosphatase activity (p < 0. 05) when compared to the control.

sodium metasilicate


Input: Additionally, all doses of sodium metasilicate (1, 5, 10, 25, 50, and 100 mu M) increased mineralized nodule formation at 14 days of differentiation as evidenced by increased Alizarin Red S staining.

sodium metasilicate

Alizarin Red S


Input: In the analysis of gene expression, 50 mu M of sodium metasilicate upregulated type I collagen (COL-I) compared to the control group.

sodium metasilicate


Input: However, the increase of COL-I gene expression as a result of treatment with 1, 10, 25, and 100 mu M of sodium metasilicate did not reach statistical significance.

sodium metasilicate


Input: mRNA expression of insulin-like growth factor-I and receptor activator of NF-kappa B ligand was not significantly changed at any dose of sodium metasilicate (0, 1, 5, 10, 25, 50, and 100 mu M).

sodium metasilicate


Input: In light of the results, we conclude that Si has a positive effect on bone metabolism by enhancing osteoblast mineralization activity.

Si


Input: Ruxolitinib: a new treatment option for myelofibrosis.

Ruxolitinib


Input: Myelofibrosis is a myeloproliferative neoplasm characterized by bone marrow fibrosis and extramedullary hematopoiesis.


Input: Evolution of myelofibrosis can lead to life-threatening complications, including transformation to leukemia, thrombotic events, and hemorrhagic episodes.


Input: The only curative therapy for myelofibrosis is allogeneic hematopoietic stem cell transplantation.


Input: Because this disease manifests primarily in the older population, many patients diagnosed with myelofibrosis are not considered medically fit for such aggressive therapy.


Input: Other available medical therapies do not halt disease progression; instead, current treatment strategies have focused on targeting specific symptomology, although with limited efficacy.


Input: The lack of effective treatment options for patients with myelofibrosis has rendered this orphan disease state an unmet medical need, and novel approaches to improve outcomes are necessary.


Input: Emerging research has identified numerous molecular mutations in patients with myelofibrosis, making this disease a potential candidate for molecularly targeted therapy.


Input: The most prevalent mutation identified is a gain-of-function mutation in the Janus kinase (JAK) family, JAK2 V617F, which has been identified in more than half of patients with myelofibrosis.


Input: This mutation results in a constitutively active JAK-signal transducer and activator of transcription pathway resulting in dysregulated cellular proliferation and hematopoiesis.


Input: Ruxolitinib is a small-molecule inhibitor of JAK1 and JAK2 and recently became the first drug approved by the United States Food and Drug Administration for the treatment of symptomatic intermediate-or high-risk myelofibrosis.

Ruxolitinib


Input: In clinical trials, ruxolitinib demonstrated promising efficacy in reducing splenomegaly and myelofibrosis-related symptoms.

ruxolitinib


Input: However, ruxolitinib did not demonstrate disease-modifying potential and is not considered a curative therapeutic option.

ruxolitinib


Input: Adverse events associated with ruxolitinib are primarily hematologic, with thrombocytopenia and anemia being the most common toxicologic events identified.

ruxolitinib


Input: Future research will shed light on whether ruxolitinib in combination with other treatments will further enhance outcomes in myelofibrosis.

ruxolitinib


Input: Prevalence of and factors that influence board certification among pharmacy practice faculty at United States colleges and schools of pharmacy.


Input: Board certification is a means of demonstrating expertise above the minimum licensing standards.


Input: For many health care professionals, this credential is a necessity.


Input: As pharmacists become involved in more advanced patient care services, board certification becomes an essential component to ensuring quality care.


Input: The prevalence of United States pharmacy practice faculty members who are board certified, however, is unknown.


Input: In addition, to our knowledge, factors that serve to motivate or discourage faculty from obtaining board certification have not been previously described; thus, 900 pharmacy practice faculty members listed in the American Association of Colleges of Pharmacy (AACP) online directory were invited to complete an online survey regarding motivators and barriers for board certification.


Input: In addition, a list of board-certified pharmacists, obtained from the Board of Pharmacy Specialties, was used to check the board certification status of all pharmacy practice faculty members listed in the AACP directory.


Input: In 2011, the prevalence of board certification among the 2867 pharmacy practice faculty members was 37% (1063 pharmacists), with the highest prevalence found among assistant professors (39. 4%). A total of 322 faculty members (36% response rate) completed the survey; of these, 308 self-identified as pharmacy practice faculty, and their responses were included in the analysis.


Input: Current board certification in pharmacy specialties was reported by 163 respondents (52. 9%); 14 (4. 5%) were previously certified.


Input: Among the 308 respondents, the most common perceived reason why pharmacy practice faculty become board certified was the desire to be recognized as an expert in the field (71. 5%).


Input: Those who were currently board certified indicated personal growth as the most important reason (60. 1%).


Input: Those previously certified indicated no perceived benefit as the most common reason for not recertifying (71. 4%).


Input: Among those never certified, no perceived need (52. 0%) or benefit (44. 8%) were the most common reasons for not becoming certified; however, a majority of those never certified (68%) stated that they would become board certified if there was no associated cost and they were confident they would pass.


Input: To increase the prevalence of board certification in pharmacy practice faculty at U. S. schools and colleges of pharmacy, the benefits of this credential must be addressed at each institution.


Input: Steps should be taken to assist and encourage board certification.


Input: Tuning optical properties of Si quantum dots by pi-conjugated capping molecules.

Si


Input: The absorption and photoluminescence (PL) properties of silicon quantum dots (QDs) are greatly influenced by their size and surface chemistry.

silicon


Input: Herein, we examined the optical properties of three Si QDs with increasing sigma-pi conjugation length: octyl-, (trimethylsilyl) vinyl-, and 2-phenylvinyl-capped Si QDs.

Si

octyl

(trimethylsilyl) vinyl

Si


Input: The PL photon energy obtained from as-prepared samples decreased by 0. 1-0. 3 eV, while the PL excitation (PLE) extended from 360 nm (octyl-capped Si QDs) to 400 nm (2-phenylvinyl-capped Si QDs).

octyl

Si

Si


Input: A vibrational PL feature was observed in all samples with an energy separation of about 0. 192 +/- 0. 013 eV, which was explained based on electron-phonon coupling.


Input: After soft oxidization through drying, all samples showed blue PL with maxima at approximately 410 nm.


Input: A similar high-energy peak was observed with the bare Si QD sample.

Si


Input: The changes in the optical properties of Si QDs were mainly explained by the formation of additional states arising from the strong sigma-pi conjugation and QD oxidation.

Si


Input: Hypoxia-selective O6-alkylguanine-DNA alkyltransferase inhibitors: design, synthesis, and evaluation of 6-(benzyloxy)-2-(aryldiazenyl)-9H-purines as prodrugs of O6-benzylguanine.

6-(benzyloxy)-2-(aryldiazenyl)-9H-purines


Input: O (6)-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein which removes alkyl groups from the O-6 position of guanine, thereby providing strong resistance to anticancer agents which alkylate this position.

O (6)-Alkylguanine

guanine


Input: The clinical usefulness of these anticancer agents would be substantially augmented if AGT could be selectively inhibited in tumor tissue, without a corresponding depletion in normal tissue.


Input: We report the synthesis of a new AGT inhibitor (5c) which selectively depletes AGT in hypoxic tumor cells.


Input: Morphological control via chemical and shear forces in block copolymer self-assembly in the lab-on-chip.


Input: We investigate the effects of variation in chemical conditions (solvent composition, water content, polymer concentration, and added salt) on the morphologies formed by PS-b-PAA in DMF/dioxane/water mixtures in a two-phase gas-liquid segmented microfluidic reactor.

PS-b-PAA

DMF

dioxane


Input: The differences in morphologies between off-chip and on-chip self-assembly and on-chip morphological trends for different chemical conditions are explained by the interplay of top-down shear effects (coalescence and breakup) and bottom-up chemical forces.


Input: Using off-chip morphology results, we construct a water content-solvent composition phase diagram showing disordered, sphere, cylinder, and vesicle regions.


Input: On-chip morphologies are found to deviate from off-chip morphologies by three identified shear-induced paths: 1) sphere-to-cylinder, and 2) sphere-to-vesicle transitions, both via shear-induced coalescence when initial micelle sizes are small, and 3) cylinder-to-sphere transitions via shear-induced breakup when initial micelle sizes are large (high capillary number conditions).


Input: These pathways contribute to the generation of large extended bilayer aggregates uniquely on-chip, at either increased polymer or salt concentrations.


Input: Collectively these results demonstrate the broad utility of top-down directed molecular self-assembly in conjunction with chemical forces to control morphology and size of polymer colloids at the nanoscale.


Input: Versatile biofunctionalization of polypeptide-based thermosensitive hydrogels via click chemistry.


Input: In this study, we report thermosensitive hydrogels based on poly (ethylene glycol)-block-poly (gamma-propargyl-l-glutamate) (PEG-PPLG).

poly (ethylene glycol)-block-poly (gamma-propargyl-l-glutamate)

PEG-PPLG


Input: (13) C NMR spectra, DLS, and circular dichroism spectra were employed to study the mechanism of the sol-gel phase transition.

(13) C


Input: Mouse fibroblast L929 cells were encapsulated and cultured within the hydrogel matrices, and the encapsulated cells were shown to be highly viable in the gel matrices, suggesting that the hydrogels have excellent cytocompatibilities.


Input: The mass loss of the hydrogels in vitro was accelerated by the presence of proteinase K compared to the control group.


Input: In vivo biocompatibility studies revealed that the in situ formed gels in the subcutaneous layer last for ~ 21 days, and H & E staining study suggested acceptable biocompatibility of our materials in vivo.


Input: The presence of alkynyl side groups in the PEG-PPLG copolymers allowed convenient further functionalization with azide-modified bioactive molecules, such as biotin and galactose.

alkynyl

PEG-PPLG

azide

biotin

galactose


Input: The biofunctionalized PEG-polypeptide block copolymers showed sol-gel phase transitions similar to the parent copolymers.

PEG


Input: Interestingly, the incorporation of galactose groups into the hydrogels was found to improve cell adhesion, likely due to the adsorption of fibronectin (FN) in cell-extracellular matrix (ECM).

galactose


Input: Because bioactive materials have shown unique advantages in biomedical applications, especially tissue engineering and regenerative medicine applications, we believe our novel functionalizable thermosensitive hydrogels have potential to serve as a versatile platform for the development of new biofunctional materials, for example, bioadhesive and bioresponsive hydrogels.


Input: Surface and tribological behaviors of the bioinspired polydopamine thin films under dry and wet conditions.

polydopamine


Input: Dopamine is a " sticky " biomolecule containing the typical functional groups of mussel adhesive proteins.

Dopamine


Input: It can self-polymerize into a nanoscale thin film on various surfaces.


Input: We investigated the surface, adhesion, friction, and cracking properties of polydopamine (PDA) thin films for their effective transfer to functional devices and biocompatible coatings.

polydopamine

PDA


Input: A series of surface characterizations and mechanical tests were performed to reveal the static and dynamic properties of PDA films coated on glass, polydimethylsiloxane (PDMS), and epoxy.

PDA

polydimethylsiloxane

PDMS

epoxy


Input: We found that PDA films are highly hydrated under wet conditions because of their porous membrane-like nanostructures and hydrophilic functional groups.

PDA


Input: Upon dehydration, the films form cracks when they are coated on soft substrates due to internal stresses and the large mismatch in elastic modulus.


Input: The adhesive pull-off force or the effective work of adhesion increased with the contact time, suggesting dynamic interactions at the interface.


Input: A significant decrease in friction forces in water was observed on all three material surfaces coated with PDA; thus, the film might serve as a water-based lubrication coating.

PDA


Input: We attributed the different behavior of PDA films in air and in water to its hydration effects.

PDA


Input: These research findings provide insight into the stability, mechanical, and adhesive properties of the PDA films, which are critical for their applications.

PDA


Input: Fine Needle Aspiration of Thyroid Nodules with Macrocalcification.


Input: Background: The presence of microcalcification is highly suggestive of malignancy; however, the association of macrocalcification with cancer remains unclear and controversial.


Input: The purpose of this study was to evaluate the diagnostic yield and accuracy of ultrasound (US)-guided fine needle aspiration (FNA) of thyroid nodules with macrocalcification and to investigate the association between macrocalcification subtype and malignancy risk.


Input: Methods: We retrospectively reviewed sonographic findings and pathologic results of thyroid nodules with macrocalcification in patients who underwent US-guided FNA in our hospital from January 2009 through December 2010.


Input: Inclusion criteria were as follows: (a) malignant or benign nodules confirmed on histologic examination of surgical specimens after US-guided FNA and (b) nodules not histologically confirmed that were subjected to FNA at least twice and follow-up US examinations for 2 years.


Input: Thyroid nodules with macrocalcification were classified into 4 groups: smooth total (eggshell) calcification, smooth partial calcification, irregular calcification, and nodular calcification.


Input: Diagnostic yield of FNA for thyroid nodules with macrocalcification was determined by cytology.


Input: Sensitivity, specificity, and diagnostic accuracy of preoperative FNA cytology were calculated and compared with those of histologic examination of surgical specimens.


Input: Results: There were 188 nodules with macrocalcification in 167 patients; of these, 95 were benign, 80 were malignant, and 13 were nondiagnostic.


Input: Diagnostic yield of FNA for thyroid nodules with macrocalcification was 93. 08%.


Input: Sensitivity, specificity, positive predictive value, and negative predictive value were 98. 51%, 90. 91%, 95. 65%, and 96. 77%, respectively.


Input: The false-positive value and false-negative value were 9. 09% and 1. 49%, respectively.


Input: The diagnostic accuracy was 96%.


Input: There was no statistically significant difference in the association between macrocalcification subtype and malignancy risk (P > 0. 05).


Input: Conclusions: Macrocalcification associated with thyroid nodules is not a reliable criterion for malignancy.


Input: FNA of thyroid nodules with macrocalcification had significantly high diagnostic yield and reliable accuracy.


Input: Consistency between FNA and histology was almost perfect.


Input: Therefore, FNA is a good screening method for malignancy of thyroid nodules with macrocalcification.


Input: Virtual walls based on oil-repellent surfaces for low-surface-tension liquids.


Input: Manipulating and controlling water-based aqueous solutions with the use of virtual walls is relatively simple compared to that of nonaqueous low-surface-tension liquids, which pose greater challenges to microfluidic devices.


Input: This letter reports a novel technique to form a virtual wall for various low-surface-tension liquids.


Input: A microfluidic channel with virtual walls has been made to guide low-surface-tension liquids by using a specially designed oil-repellent surface.


Input: Unlike generic superoleophobic surfaces, our oil-repellent surface exhibited strong repellency to the lateral flow of low-surface-tension liquids such as hexadecane and dodecane.

hexadecane

dodecane


Input: A plasma-assisted surface micromachining process has been utilized to form the oil-repellent surface.


Input: The use of combined features of re-entrant geometries on the surface played an important role in promoting its repellence to the lateral flow of low-surface-tension liquids.


Input: We have successfully demonstrated how low-surface-tension liquids can be well confined by the virtual walls.


Input: Evaluation of Coumarin and Neoflavone Derivatives as HCV NS5B Polymerase Inhibitors.

Coumarin

Neoflavone


Input: Coumarins and coumestans represent an important family of compounds with diverse pharmacological properties.

Coumarins

coumestans


Input: We recently identified coumestans as novel inhibitors of hepatitis C virus NS5B polymerase and predicted their binding in thumb pocket-1 (TP-1) of NS5B.

coumestans


Input: As the coumarins are structurally related to coumestans by virtue of their common A-and B-rings, we postulated them to also exhibit similar binding interaction with NS5B and inhibit its polymerase function.

coumarins

coumestans


Input: We therefore investigated 24 coumarin and neoflavone derivatives as candidate NS5B inhibitors and identified 14 compounds inhibiting NS5B polymerase activity with IC50 values between 17 and 63 mu m.

coumarin

neoflavone


Input: Of these, the newly synthesized 6, 8-diallyl-5, 7-dihydroxycoumarin (8a) was produced in three steps in high chemical yield from floroglucinol and found to be the most potent of this series, exhibiting activity similar to the reference coumestan LQB-34.

6, 8-diallyl-5, 7-dihydroxycoumarin

floroglucinol

coumestan LQB-34


Input: The binding site of 8a was mapped to TP-1 of NS5B by counter screening against P495L NS5B mutant, employed as a screen for TP-1 site binders.


Input: NS5B-TP-1-8a interaction map provided insight into 8a binding and offered clues for future SAR optimization.


Input: Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation.

Trimethylamine-N-oxide


Input: Circulating trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis.

trimethylamine-N-oxide

TMAO


Input: We now examine genetic, dietary, and hormonal factors regulating TMAO levels.

TMAO


Input: We demonstrate that two flavin mono-oxygenase family members, FMO1 and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to TMAO.

flavin

trimethylamine

TMA

choline

TMAO


Input: Further, we show that FMO3 exhibits 10-fold higher specific activity than FMO1.


Input: FMO3 overexpression in mice significantly increases plasma TMAO levels while silencing FMO3 decreases TMAO levels.

TMAO

TMAO


Input: In both humans and mice, hepatic FMO3 expression is reduced in males compared to females.


Input: In mice, this reduction in FMO3 expression is due primarily to downregulation by androgens.

androgens


Input: FMO3 expression is induced by dietary bile acids by a mechanism that involves the farnesoid X receptor (FXR), a bile acid-activated nuclear receptor.

bile acids

bile acid


Input: Analysis of natural genetic variation among inbred strains of mice indicates that FMO3 and TMAO are significantly correlated, and TMAO levels explain 11% of the variation in atherosclerosis.

TMAO

TMAO


Input: Identification of N-acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine derivatives and their orally active prodrug esters as dual-acting alpha4-beta1 and alpha4-beta7 receptor antagonists.

N-acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine

esters


Input: N-Acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine derivatives of type 4 were designed to replace the 2, 6-dichlorobenzoylamine portion of compound 1 in order to identify novel compounds with improved potency against alpha 4-integrins.

N-Acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine

2, 6-dichlorobenzoylamine


Input: Several derivatives were identified as very potent dual-acting alpha 4-integrin, alpha 4 beta 1 and alpha 4 beta 7 antagonists.


Input: Investigation of a limited number of prodrug esters led to the discovery of the ethyl ester prodrug 42, which demonstrated good intestinal fluid stability and good permeability.

ethyl ester


Input: Despite low solubility, 42 gave acceptable blood levels of 30 when dosed orally in non-human primates.


Input: Additionally, 42 had an overall excellent profile and was selected for clinical trials.


Input: Investigation of N-acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine derivatives led to the discovery of several very potent dual-acting alpha 4-integrin antagonists.

N-acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine


Input: Ethyl ester prodrug 42 advanced to human clinical trials based on the excellent intestinal fluid stability, good permeability and superior efficacy in non-human primates.

Ethyl ester


Input: Tricycloalternarenes F-H: three new mixed terpenoids produced by an endolichenic fungus Ulocladium sp. using OSMAC method.

Tricycloalternarenes F-H

terpenoids


Input: Three new mixed terpenoids, tricycloalternarenes (TCAs) F-H (1-3), together with ten known tricycloalternarenes (4-13), were isolated from the Czapek' s culture of an endophytic fungus Ulocladium sp.

terpenoids

tricycloalternarenes

TCAs

tricycloalternarenes


Input: Their structures were identified by extensive spectroscopic experiments (NMR and MS) and comparison with literature data.


Input: TCA 1b (5) showed weak activity against the Bacille Calmette-Guerin strain with the MIC of 125 mu g/mL.

TCA


Input: TCA 9b (10) exhibited strong cytotoxic activity against Hela cell line with IC50 of 8. 58 mu M.

TCA


Input: Aphagrandinoids A-D, cycloartane triterpenoids with antibacterial activities from Aphanamixis grandifolia.

Aphagrandinoids A-D

cycloartane triterpenoids


Input: Three new cycloartane triterpenoids, aphagrandinoids A-C (1-3), and a new natural product, aphagrandinoid D (4), together with a known compound, were isolated from the leaves and twigs of Aphanamixis grandifolia.

cycloartane triterpenoids

aphagrandinoids A-C

aphagrandinoid D


Input: Their structures were elucidated by extensive NMR and MS techniques.


Input: Aphagrandinoid A (1), a 29-nor-cycloart triterpenoid, features with a sprio ring system at the side chain, while aphagrandinoid C (3) is a pentnortriterpenoid.

Aphagrandinoid A

29-nor-cycloart triterpenoid

aphagrandinoid C

pentnortriterpenoid


Input: Antibacterial activities of these five compounds were also evaluated.


Input: Compounds 1 and 5 showed weak antibacterial activities (MIC values: 1. 57-3. 13 mu g/mL) against Staphylococcus aureus, MRSA 92 (#), and MRSA 98 (#).


Input: What are the physiological estrogens?

estrogens


Input: Estradiol (E2) is the principal physiological estrogen in mammals.

Estradiol


Input: E2 and its active metabolites, estrone and estriol have a characteristic phenolic A ring, unlike progesterone, testosterone, cortisol and aldosterone, which have an A ring containing a C3-ketone, a Delta (4) bond and a C19 methyl group.

estrone

estriol

progesterone

testosterone

cortisol

aldosterone

ketone

methyl


Input: Crystal structures of E2 in the estrogen receptor (ER) confirm the importance of the A ring in stabilizing E2 in the ER.

estrogen


Input: However, other steroids, including Delta (5)-androstenediol, 5 alpha-androstanediol and 27-hydroxycholesterol, which have a saturated A ring containing a 3 beta-hydroxyl and a C19 methyl group, also mediate physiological responses through binding to estrogen receptor-alpha (ER alpha) and ER beta.

steroids

Delta (5)-androstenediol

5 alpha-androstanediol

3 beta-hydroxyl

methyl

estrogen


Input: Moreover, selective estrogen response modulators (SERMs) with diverse structures also regulate transcription of ER alpha and ER beta.

estrogen


Input: Our understanding of the physiological responses mediated by these " alternative " estrogens is in its infancy.

estrogens


Input: Further studies of the role of these steroids and SERMs in regulating responses mediated by ER alpha and ER beta a variety of tissues, during different stages of development, are likely to uncover additional estrogenic activities.

steroids


Input: Perturbation of male sexual behavior in mice (Mus musculus) within a discrete range of perinatal bisphenol-A doses in the context of a high-or low-phytoestrogen diet.

bisphenol-A


Input: Differentiation of masculine and feminine behavior in mammals depends on perinatal sex steroids.

steroids


Input: As bisphenol-A (BPA) can be estrogenic and anti-androgenic, we examined impacts of perinatal exposure upon adult sexual behavior and morphology of male mice.

bisphenol-A

BPA


Input: In Experiment 1, dams were fed either a high-or low-phytoestrogen diet and received daily oral doses of 0, 0. 175, 1. 75, or 17. 5 mu g BPA from gestation day 10 through post-partum day 9.

BPA


Input: Male offspring from the high-phytoestrogen plus 17. 5 mu g BPA condition showed reduced mass of vesicular-coagulating but not other male glands, and showed increased latency to insemination when paired with females.

BPA


Input: In Experiment 2, these procedures were replicated but with all animals fed the high-phytoestrogen diet and perinatal BPA doses of 0, 17. 5, 175, or 1750 mu g/day.

BPA


Input: Adult masses of testes and male-accessory glands and levels of urinary steroids were not significantly affected.

steroids


Input: When males each encountered a sexually receptive female, there were fewer intromissions among those given 17. 5 or 175 mu g and fewer ejaculations among those given 17. 5 mu g, but the 1750 mu g dose had no effect.


Input: Perinatal BPA dosages thus influenced male sexual behavior non-monotonically, with impairment evident in a discrete dose range among males on a high-phytoestrogen diet.

BPA


Input: Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury.


Input: Traumatic brain injury (TBI) induces primary and secondary damage in both the endothelium and the brain parenchyma.


Input: While neurons die quickly by necrosis, a vicious cycle of secondary injury in endothelial cells exacerbates the initial injury.


Input: Thyroid hormones are reported to be decreased in patients with brain injury.


Input: Controlled cortical impact injury (CCI) is a widely used, clinically relevant model of TBI.


Input: Here, using CCI in adult male mice, we set to determine whether 3, 5, 3'-triiodothyronine (T3) attenuates posttraumatic neurodegeneration and neuroinflammation in an experimental model of TBI.

3, 5, 3'-triiodothyronine


Input: Treatment with T3 (1. 2 mu g/100g body weight, i. p.) 1h after TBI resulted in a significant improvement in motor and cognitive recovery after CCI, as well as in marked reduction of lesion volumes.


Input: Mouse model for brain injury showed reactive astrocytes with increased glial fibrillary acidic protein, and formation of inducible nitric oxide synthase (iNOS).

nitric oxide


Input: Western blot analysis revealed the ability of T3 to reduce brain trauma through modulation of cytoplasmic-nuclear shuttling of nuclear factor-kappa B (NF-kappa B).


Input: Twenty-four hours after brain trauma, T3-treated mice also showed significantly lower number of TUNEL (+) apoptotic neurons and curtailed induction of Bax, compared to vehicle control.


Input: In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle.


Input: Our data provide an additional mechanism for the anti-inflammatory effects of thyroid hormone with critical implications in immunopathology at the cross-roads of the immune-endocrine circuits.


Input: Lipopolysaccharide-induced acute lung injury in rats: comparative assessment of intratracheal instillation and aerosol inhalation.


Input: Acute lung injury (ALI) has many possible etiopathologies and is characterized by acute diffuse lung damage with poor prognosis.


Input: Lipopolysaccharide (LPS) is widely used as septic model of ALI in pharmacological research.


Input: This study compares intratracheal bolus instillation (IT) with dose-adjusted aerosol inhalation (IH) of LPS in Wistar rats using both non-invasive and terminal endpoints.


Input: The former comprised exhaled nitric oxide (NOE) and' enhanced pause' (Penh) both measured in spontaneous breathing conscious rats.

nitric oxide


Input: Terminal endpoints included lung weights, LDH, protein, total cell counts, and cytodifferentiation in bronchoalveolar lavage (BAL).


Input: Measurements were made 1, 3, 7, and 14 days after IT instillation (5 mg LPS/kg body weight) or 6-hour directed-flow nose-only inhalation exposure to respirable LPS-aerosol at 100 mg/m (3) (thoracic dose: 2. 6 mgLPS/kg body weight).


Input: Controls received saline (IT) or air only (IH).


Input: LDH and protein were significantly different from the control in the LPS-IH group (days 1 and 3) with a somewhat inconclusive outcome in the LPS-IT group due to the effects occurring in the control.


Input: Total cell counts were equally elevated with similar time-course changes in the LPS-IT and-IH groups.


Input: Polymorphonuclear neutrophils (PMNs) were indistinguishable amongst LPS-dosed rats.


Input: Again, IT-dosed control rats displayed markedly higher background levels than those dosed by inhalation.


Input: Similarly NOE was significantly elevated on post-LPS day 1 as was Penh.


Input: In summary, the LPS-aerosol dose delivered by nose-only exposure over 6 h was equally potent as the 2-times higher LPS-IT bolus dose on post-LPS day 1 with somewhat faster recovery thereafter.


Input: The climax and discriminatory power of the non-invasive endpoints matched those determined terminally.


Input: This supports the conclusion that the pharmacological efficacy and side effects of inhalation pharmaceuticals designed to mitigate ALI can better be identified by LPS-aerosol than by LPS-IT.


Input: Non-invasive time-course measurements may deliver apt information both on the efficacious dose as well as the dosing intervals required to maintain the targeted efficacy using a minimum of experimental animals.


Input: The outcome of this comparative study supports the conclusion that the inhalation route produces a more uniform type of injury at lower, more meaningful dosages.


Input: When designing studies for screening of effective drugs this mode of delivery appears to better approximate the human condition with less dosimetric uncertainty, less experimental variability and better characterization of what was actually delivered to the entire respiratory tract.


Input: (-)-Xanthatin up-regulation of the GADD45 gamma tumor suppressor gene in MDA-MB-231 breast cancer cells: role of topoisomerase II alpha inhibition and reactive oxygen species.

(-)-Xanthatin

oxygen


Input: Previously, we reported that (-)-xanthatin, a naturally occurring xanthanolide present in the Cocklebur plant, exhibits potent anti-proliferative effects on human breast cancer cells, accompanied by an induction of the growth arrest and DNA damage-inducible gene 45 gamma (GADD45 gamma), recognized recently as a novel tumor suppressor gene.

(-)-xanthatin

xanthanolide


Input: However, the mechanisms mediating this activation were unknown.


Input: Topoisomerase II alpha (Topo II alpha) inhibition has been reported to produce a cell death response accompanied by an atypical DNA laddering fragmentation profile, similar to that noted previously for (-)-xanthatin.

(-)-xanthatin


Input: Therefore we hypothesized that (-)-xanthatin' s GADD45 gamma activation was mediated through the Topo II alpha pathway.

(-)-xanthatin


Input: Here, we identify that (-)-xanthatin does function as a catalytic inhibitor of Topo II alpha, promoting DNA damage.

(-)-xanthatin


Input: In addition, reactive oxygen species (ROS) were elevated in cells treated with this agent.

oxygen


Input: Mechanistically, it was determined that the induced levels of GADD45 gamma mRNA resulting from (-)-xanthatin exposures were stabilized by coordinately produced ROS, and that the consequent induction of GADD45 gamma mRNA, GADD45 gamma protein and ROS generation were abrogated by co-treatment with N-acetyl-l-cysteine.

(-)-xanthatin

N-acetyl-l-cysteine


Input: Taken together, the data support the concept that Topo II alpha inhibition by (-)-xanthatin is a trigger that stimulates expression of DNA damage-inducible GADD45 gamma mRNA and that concomitantly produced ROS act downstream to further enhance the GADD45 gamma mRNA/GADD45 gamma protein induction process, resulting in breast cancer cell death.

(-)-xanthatin


Input: Antioxidant, antimicrobial and anti-proliferative activities of Solanum tuberosum L. var.


Input: Vitelotte.


Input: Solanum tuberosum L. var.


Input: Vitelotte is a potato variety widely used for human consumption.


Input: The pigments responsible for its attractive color belong to the class of anthocyanins.

anthocyanins


Input: The objectives of this study were to characterize and measure the concentration of anthocyanins in pigmented potatoes and to evaluate their antioxidant and antimicrobial activities and their anti-proliferative effects in solid and hematological cancer cell lines.

anthocyanins


Input: Anthocyanins exert anti-bacterial activity against different bacterial strains and a slight activity against three fungal strains.

Anthocyanins


Input: The Gram-positive bacterium Staphylococcus aureus and the fungus Rhyzoctonia solani were the most affected microorganisms.


Input: Antioxidant activities were evaluated by DPPH and FRAP methods; the extract showed a higher reducing capability than anti-radical activity.

DPPH


Input: Moreover, we found that in different cancer cell models the anthocyanins cause inhibition of proliferation and apoptosis in a dose dependent manner.

anthocyanins


Input: These biological activities are likely due to the high content of malvidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside and petunidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside.

malvidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside

petunidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside


Input: Asymmetric synthesis and anti-protozoal activity of the 8, 4'-oxyneolignans virolin, surinamensin and analogues.

8, 4'-oxyneolignans virolin

surinamensin


Input: The asymmetric synthesis of 8, 4'-oxyneolignans (-)-virolin, (-)-surinamensin and a number of analogues has been achieved.

8, 4'-oxyneolignans (-)-virolin

(-)-surinamensin


Input: A divergent synthesis was used, with all compounds being elaborated from a single chiral aldehyde derived from ethyl lactate.

aldehyde

ethyl lactate


Input: In the 15 compounds that were tested, the level of substitution on the A-ring was found to directly influence the activity against Leishmania donovani whilst the activity against Plasmodium falciparum was influenced by numerous substitution and stereochemical factors.


Input: Predictive modeling of insulin release profile from cross-linked chitosan microspheres.


Input: Insulin-loaded microspheres composed of chitosan 3% (w/v), and loading 120 IU insulin were produced by emulsion cross-linking method.


Input: Cross-linking time was 5 h and glutaraldehyde 3. 5% (v/v) was used as cross-linker.

glutaraldehyde


Input: Swelling ratio studies were evaluated to predict release of insulin from chitosan microspheres.


Input: Bacitracin and sodium taurocholate were incorporated in the formulations as proteolytic enzyme inhibitor and absorption enhancer, respectively.

Bacitracin

sodium taurocholate


Input: In vitro insulin release studies were performed in phosphate buffer pH 7. 4 and also in HCl pH 2 with and without trypsin.

phosphate

HCl


Input: Activity of bacitracin was also evaluated.

bacitracin


Input: In vitro release showed a controlled profile up to 12 h and the formulation containing 0. 15% (w/v) of bacitracin revealed a maximum biological activity of about 49. 1 +/- 4. 1%.

bacitracin


Input: Mathematical modeling using Higuchi and Korsmeyer-Peppas suggested a non-Fickian diffusion as the mechanism of insulin release.


Input: Insulin-loaded chitosan microspheres for oral delivery showed to be an innovative and reliable delivery system to overcome conventional insulin therapy.


Input: A systematic identification of multiple toxin-target interactions based on chemical, genomic and toxicological data.


Input: Although the assessment of toxicity of various agents,-omics (genomic, proteomic, metabolomic, etc.) data has been accumulated largely, the acquirement of toxicity information of variety of molecules through experimental methods still remains a difficult task.


Input: Presently, a systems toxicology approach that integrates massive diverse chemical, genomic and toxicological information was developed for prediction of the toxin targets and their related networks.


Input: The procedures are: (1) by use of two powerful statistical methods, i. e., support vector machine (SVM) and random forest (RF), a systemic model for prediction of multiple toxin-target interactions using the extracted chemical and genomic features has been developed with its reliability and robustness estimated.


Input: And the qualitative classification of targets according to the phenotypic diseases has been taken into account to further uncover the biological meaning of the targets, as well as to validate the robustness of the in silico models.


Input: (2) Based on the predicted toxin-target interactions, a genome-scale toxin-target-disease network exampled by cardiovascular disease is generated.


Input: (3) A topological analysis of the network is carried out to identify those targets that are most susceptible in human to topical agents including the most critical toxins, as well as to uncover both the toxin-specific mechanisms and pathways.


Input: The methodologies presented herein for systems toxicology will make drug development, toxin environmental risk assessment more efficient, acceptable and cost-effective.


Input: In vitro and ex vivo models of human asthma.


Input: Asthma is an inflammatory disorder of the conducting airways which undergo distinct structural and functional changes leading to non-specific bronchial hyperresponsiveness (BHR) and airflow obstruction that fluctuate over time.


Input: It is a complex disease involving multiple genetic and environmental influences whose multifactorial interactions can result in a range of asthma phenotypes.


Input: Since our understanding of these gene-gene and gene-environment interactions is very poor, this poses a major challenge to the logical development of' models of asthma'.


Input: However, use of cells and tissues from asthmatic donors allows genetic and epigenetic influences to be evaluated and can go some way to reflect the complex interplay between genetic and environmental stimuli that occur in vivo.


Input: Current alternative approaches to in vivo animal models involve use of a plethora of systems ranging from very simple models using human cells (e. g. bronchial epithelial cells and fibroblasts) in mono-or co-culture, whole tissue explants (biopsies, muscle strips, bronchial rings) through to in vivo studies in human volunteers.


Input: Asthma research has been greatly facilitated by the introduction of fibreoptic bronchoscopy which is now a commonly used technique in the field of respiratory disease research, allowing collection of biopsy specimens, bronchial brushing samples, and bronchoalveolar lavage fluid enabling use of disease-derived cells and tissues in some of these models.


Input: Here, we will consider the merits and limitations of current models and discuss the potential of tissue engineering approaches through which we aim to advance our understanding of asthma and its treatment.


Input: Effects of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) on histopathology, oxidative stress, and expression of c-fos, c-jun and p16 in rat stomachs.

2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine

PhIP


Input: 2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is one of the most abundant heterocyclic amines (HCAs) generated from overcooking meat at high temperatures.

2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine

PhIP

heterocyclic amines

HCAs


Input: To understand the possible mechanism of PhIP-associated stomach cancer, the effects of PhIP on morphology, oxidative stress, gene expression of c-fos, c-jun and p16 in rat stomachs were investigated.

PhIP

PhIP


Input: The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) PhIP (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control.

PhIP

PhIP

superoxide


Input: With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) PhIP at the doses of 10mg/kg and/or 15mg/kg significantly inhibited p16 mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control.

PhIP

malondialdehyde

MDA

carbonyl

PhIP


Input: The data indicated that PhIP could cause stomach injury, oxidative stress in rat stomachs as well as the activation of c-fos and c-jun and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer.

PhIP

PhIP


Input: Diminutive effect on T and B-cell proliferation of non-cytotoxic alpha-santonin derived 1, 2, 3-triazoles: a report.

alpha-santonin

1, 2, 3-triazoles


Input: alpha-Santonin derived new series of 1, 2, 3-triazoles synthesized through Azide-Alkyne Huisgen 1, 3-dipolar cycloaddition reaction between substituted aryl azide and a propargylated alpha-desmotrosantonin were bio-evaluated for their diminutive effect on ConA induced T-cell and LPS induced B-cell proliferation.

alpha-Santonin

1, 2, 3-triazoles

Azide-Alkyne

aryl azide

propargylated alpha-desmotrosantonin


Input: Interestingly, most of the synthesized compounds showed better immunosuppressant activity than alpha-santonin.

alpha-santonin


Input: Triazole derivatives 9, 10, 17, 18, 29, and 30 displayed significant diminutive effect on cell proliferation.

Triazole


Input: Compounds 12 and 13 were found selective against ConA T-cell proliferation exhibiting > 90% inhibition at 1 x 10 (-6) M concentration.


Input: The present study resulted in identification of several triazole derivatives as effective immunosuppressive agents.

triazole


Input: Tributyltin exposure influences predatory behavior, neurotransmitter content and receptor expression in Sebastiscus marmoratus.

Tributyltin


Input: Tributyltin (TBT) is a ubiquitous marine contaminant due to its extensive use as a biocide, fungicide and antifouling agent.

Tributyltin

TBT


Input: However, the neurotoxic effect of TBT has not been extensively studied, especially in marine fish.

TBT


Input: This study was conducted to investigate the effects of TBT (10, 100 and 1000 ng/L) on the predatory behavior of Sebastiscus marmoratus and to look into the mechanism involved.

TBT


Input: The results showed that TBT exposure depressed predatory activity after 50 days exposure.

TBT


Input: Dopamine levels in the fish brains increased in a dose-dependent manner, while 5-hydroxytryptamine and norepinephrine levels decreased significantly in the TBT exposure group compared to the control.

Dopamine

norepinephrine

TBT


Input: The mRNA levels of dopamine receptors, which have functions such as cognition, motor activity, motivation and reward, mood, attention and learning, were significantly down-regulated by TBT exposure.

dopamine

TBT


Input: Although the levels of amino acid neurotransmitters, including glutamate, did not show marked alteration, the expression of the glutamatergic signaling pathway such as N-methyl-D-aspartate receptors, a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, calmodulin, Ca (2 +)/calmodulin-dependent protein kinases-II and cyclic adenosine monophosphate responsive element binding protein, was significantly reduced by TBT exposure, which indicated that central nerve activities were in a state of depression, thus affecting the predatory activities of the fish.

amino acid

glutamate

N-methyl-D-aspartate

a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid

Ca (2 +)

cyclic adenosine monophosphate

TBT


Input: Electrical field stimulation (EFS)-induced relaxations turn into contractions upon removal of extracellular calcium in rat mesenteric artery.

calcium


Input: In the present study, we aimed to examine the effect of blockade of L-type Ca (2 +) channels (LTCC) and in addition the removal of extracellular Ca (2 +), on EFS-induced relaxations in rings of rat mesenteric artery.

Ca (2 +)

Ca (2 +)


Input: EFS applied to the tissues precontracted with phenylephrine caused relaxations which were markedly inhibited by nifedipine (10 (-7) M) and tetraethylammonium (TEA) (1mM).

phenylephrine

nifedipine

tetraethylammonium

TEA


Input: Addition of LTCC opener BAY K 8644 (10 (-7) M) failed to enhance the relaxations.

BAY K 8644


Input: Upon removal of Ca (2 +), EFS with the same stimulation parameters produced frequency-dependent transient contractions.

Ca (2 +)


Input: Tetrodotoxin (10 (-6) M), capsaicin (10 (-5) M) and removal of endothelium did not alter these contractions suggesting that they were not neural in origin and endothelium-derived contracting factors were unlikely to be involved.

Tetrodotoxin

capsaicin


Input: However, they were increased by nearly 40% in response to BAY K 8644 (10 (-7) M) and were inhibited by nifedipine (10 (-7) M), indicating that activation of the LTCCs was essential.

BAY K 8644

nifedipine


Input: Inositol triphosphate (InsP3) receptor antagonist 2-APB (10 (-4) M) significantly reduced, and high concentration of caffeine (20mM) almost totally suppressed the contractions.

Inositol triphosphate

caffeine


Input: These results suggest that in the absence of extracellular Ca (2 +) EFS through membrane depolarization, evokes the opening of the LTCCs which subsequently leads to the release of Ca (2 +) from internal stores via InsP3 receptors, a phenomenon known as Ca (2 +) channel-induced Ca (2 +) release (CCICR), to trigger vasoconstriction.

Ca (2 +)

Ca (2 +)

Ca (2 +)

Ca (2 +)


Input: That activation of LTCCs causes arterial relaxation or contraction depending on the Ca (2 +) status apparently exemplifies how the same messenger fulfils opposing physiological functions in a given cell.

Ca (2 +)


Input: Occupational exposure to pentachlorophenol causing lymphoma and hematopoietic malignancy for two generations.

pentachlorophenol


Input: OBJECTIVE: Pentachlorophenol (PCP) is characterized as likely carcinogen of lymphoma and hematopoietic neoplasm.

Pentachlorophenol

PCP


Input: But the carcinogenicity to human was uncertain based on population studies.


Input: A systematic review was conducted to explore two kinds of associations, one was between the workers exposed to PCP with lymphoma and hematopoietic neoplasm, the other was between childhood lymphoma and leukemia with their parents exposed to PCP.

PCP

PCP


Input: METHODS: Systematic search for epidemiologic studies was carried out and the data were collected from MEDLINE database and from the reference lists of relevant studies.


Input: Data were extracted from 20 included studies published between 1986 and 2012.


Input: RESULTS: The meta-analysis suggested a significant association between lymphoma and workers' occupational exposing to PCP, for the pooled odds ratio = 2. 57 (95% confidence interval (CI) = 1. 52-4. 35).

PCP


Input: The subgroup analysis indicated significant association for non-Hodgkin' s lymphoma, but not for Hodgkin' s disease.


Input: The cohort studies also showed comparatively higher relative risk (RR) and standardized mortality ratio (SMR).


Input: Two of the cohort studies found increased RR as the cumulative exposure time added.


Input: Another cohort study discovered that the white males had significantly elevated non-Hodgkin' s lymphoma mortality (SMR = 1. 98, 95% CI = 1. 15-3. 17), and males of other races had increased leukemia mortality (SMR = 4. 57, 95% CI = 1. 25-11. 7).


Input: For the relationship of childhood leukemia and parental exposure to PCP, three published studies suggested an increased risk of childhood leukemia because of their parental exposure to PCP at the preconception period.

PCP

PCP


Input: CONCLUSION: Our review provided the evidence that occupational exposure of workers to PCP might increase the risk of lymphoma and hematopoietic neoplasm in themselves and in their children.

PCP


Input: Silica nanoparticles-induced cytotoxicity, oxidative stress and apoptosis in cultured A431 and A549 cells.

Silica


Input: In medicine, the use of silica nanoparticles (SiO (2) NPs) offers new perspectives in biosensor, drug delivery and cancer therapy.

silica

SiO (2)


Input: However, questions about potential toxic and deleterious effects of SiO (2) NPs have also been raised.

SiO (2)


Input: The aim of this study was to investigate the induction of cytotoxicity, oxidative stress and apoptosis by SiO (2) NPs (size 15 nm) in human skin epithelial (A431) and human lung epithelial (A549) cells.

SiO (2)


Input: SiO (2) NPs (concentration range 25-200 micro g/ml) induced dose-dependent cytotoxicity in both types of cells, which was demonstrated by cell viability (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide) and lactate dehydrogenase leakage assays.

SiO (2)

3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide

lactate


Input: SiO (2) NPs were also found to induce oxidative stress in a dose-dependent manner, indicated by depletion of glutathione and induction of reactive oxygen species (ROS) generation and lipid peroxidation.

SiO (2)

glutathione

oxygen


Input: Quantitative real-time polymerase chain reaction analysis showed that following the exposure of cells to SiO (2) NPs, the messenger RNA level of apoptotic genes (caspase-3 and caspase-9) were upregulated in a dose-dependent manner.

SiO (2)


Input: Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in both kinds of cells exposed to SiO (2) NPs.

SiO (2)


Input: This study suggested that SiO (2) NPs induce cytotoxicity and apoptosis in A431 and A549 cells, which is likely to be mediated through ROS generation and oxidative stress.

SiO (2)


Input: Decreased RB1 mRNA, Protein, and Activity Reflect Obesity-Induced Altered Adipogenic Capacity in Human Adipose Tissue.


Input: Retinoblastoma (Rb1) has been described as an essential player in white adipocyte differentiation in mice.


Input: No studies have been reported thus far in human adipose tissue or human adipocytes.


Input: We aimed to investigate the possible role and regulation of RB1 in adipose tissue in obesity using human samples and animal and cell models.


Input: Adipose RB1 (mRNA, protein, and activity) was negatively associated with BMI and insulin resistance (HOMA-IR) while positively associated with the expression of adipogenic genes (PPAR gamma and IRS1) in both visceral and subcutaneous human adipose tissue.


Input: BMI increase was the main contributor to adipose RB1 downregulation.


Input: In rats, adipose Rb1 gene expression and activity decreased in parallel to dietary-induced weight gain and returned to baseline with weight loss.


Input: RB1 gene and protein expression and activity increased significantly during human adipocyte differentiation.


Input: In fully differentiated adipocytes, transient knockdown of Rb1 led to loss of the adipogenic phenotype.


Input: In conclusion, Rb1 seems to play a permissive role for human adipose tissue function, being downregulated in obesity and increased during differentiation of human adipocytes.


Input: Rb1 knockdown findings further implicate Rb1 as necessary for maintenance of adipogenic characteristics in fully differentiated adipocytes.


Input: Complex II of the mitochondrial respiratory chain is the key mediator of divalent manganese-induced hydrogen peroxide production in microglia.

divalent manganese

hydrogen peroxide


Input: Exposure to excessive levels of manganese (Mn) is associated with the development of movement disorders, with symptoms overlapping with Parkinson' s disease.

manganese

Mn


Input: Oxidative damage has been implicated as a key contributor to Mn-induced neurotoxicity.

Mn


Input: We have recently reported that divalent Mn (Mn (2 +)) stimulates brain microglia to produce and release hydrogen peroxide (H2O2), and microglial-free radical generation facilitates Mn (2 +)-induced dopaminergic neurotoxicity.

divalent Mn

Mn (2 +)

hydrogen peroxide

Mn (2 +)


Input: The goal of this study was to elucidate the underlying mechanism of the Mn (2 +)-induced H2O2 production in microglia.

Mn (2 +)


Input: Exposure to low micromolar concentrations of Mn (2 +), but not divalent copper, cadmium, nickel, cobalt, zinc, and iron, induced a significant production of H2O2 from rat microglial but not astroglial cells.

Mn (2 +)

divalent copper, cadmium, nickel, cobalt, zinc, and iron


Input: Subcellular fractionation studies revealed that Mn (2 +) was capable of inducing significant H2O2 production in the mitochondrial but not the cytosolic or nuclear fraction prepared from microglia.

Mn (2 +)


Input: Analysis of the relative contribution of mitochondrial respiratory chain complexes indicated that Mn (2 +)-induced mitochondrial H2O2 production required the presence of complex II substrate succinate.

Mn (2 +)

succinate


Input: In contrast, complex I substrates malate and glutamate failed to support H2O2 production in the presence of Mn (2 +).

malate

glutamate

Mn (2 +)


Input: Furthermore, the succinate-supported Mn (2 +)-induced mitochondrial H2O2 production was abolished by pharmacological inhibition of complex II but not that of complexes I and III, suggesting that mitochondrial complex II is a key mediator in Mn (2 +)-induced H2O2 production.

succinate

Mn (2 +)

Mn (2 +)


Input: These findings advance our knowledge on the mechanisms by which Mn induces oxidative stress and the potential contribution to Mn neurotoxicity.

Mn


Input: Phenotypic profiling of structural cardiotoxins in vitro reveals dependency on multiple mechanisms of toxicity.


Input: Morphological damage to cardiomyocytes or loss of viability (structural cardiotoxicity) is a common cause of attrition in preclinical and clinical drug development.


Input: Currently, no predictive in vitro approaches are available to detect this liability early in drug discovery, and knowledge of the mechanisms involved is limited.


Input: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and the rat myoblastic H9c2 cell lines were used to phenotypically profile a panel of structural cardiotoxins by live-cell fluorescent imaging of mitochondrial membrane potential, endoplasmic reticulum integrity, Ca (2 +) mobilization, and membrane permeability combined with an assessment of cell viability (ATP depletion).

Ca (2 +)

ATP


Input: Assay results were normalized to known therapeutically relevant concentrations.


Input: By comparing the outcome of each assay to the known in vivo effects, hESC-CMs offered an improved model over H9c2 cells for the detection of structural cardiotoxicity at therapeutically relevant concentrations.


Input: Inhibition of the spontaneously beating phenotype, a feature of stem cell-derived cardiomyocytes, revealed some degree of cardioprotection following 10 out of 13 structural cardiotoxins, illustrating the intricate relationship between the function and structure of cardiomyocytes.


Input: Classification of structural cardiotoxins into mechanistic themes revealed mitochondria and calcium mobilization to be major distal targets, with only 4 out of 15 compounds affecting contractile function in freshly isolated canine cardiomyocytes at therapeutically relevant concentrations.

calcium


Input: Our data demonstrate the utility of hESC-CMs during drug development to support structural cardiotoxicity hazard identification and to gain insight into the intricate mechanisms implicated in structural cardiotoxicity.


Input: Paternal Metabolic and Cardiovascular Risk Factors for Fetal Growth Restriction: A case-control study.


Input: OBJECTIVEFathers of low-birth weight offspring are more likely to have type 2 diabetes and cardiovascular disease in later life.


Input: We investigated whether paternal insulin resistance and cardiovascular risk factors were evident at the time that fetal growth-restricted offspring were born. RESEARCH DESIGN AND METHODSWe carried out a case-control study of men who fathered pregnancies affected by fetal growth restriction, in the absence of recognized fetal disease (n = 42), compared with men who fathered normal-birth weight offspring (n = 77).


Input: All mothers were healthy, nonsmoking, and similar in age, BMI, ethnicity, and parity.


Input: Within 4 weeks of offspring birth, all fathers had measures of insulin resistance (HOMA index), blood pressure, waist circumference, endothelial function (flow-mediated dilatation), lipid profile, weight, and smoking habit.


Input: Comparison was made using multivariable logistical regression analysis. RESULTSFathers of fetal growth-restricted offspring [mean (SD) 1. 8th (2. 2) customized birth centile] were more likely to have insulin resistance, hypertension, central adiposity, and endothelial dysfunction and to smoke cigarettes compared with fathers of normal grown offspring.


Input: After multivariable analysis, paternal insulin resistance and smoking remained different between the groups.


Input: Compared with fathers of normal grown offspring, men who fathered pregnancies affected by fetal growth restriction had an OR 7. 68 (95% CI 2. 63-22. 40; P < 0. 0001) of having a 1-unit higher log HOMA-IR value and 3. 39 (1. 26-9. 16; P = 0. 016) of being a smoker. CONCLUSIONSMen who recently fathered growth-restricted offspring have preclinical evidence of the insulin resistance syndrome and are more likely to smoke than fathers of normal grown offspring.


Input: Paternal lifestyle may influence heritable factors important for fetal growth.


Input: Characterization of four new mouse cytochrome P450 enzymes of the CYP2J subfamily.


Input: The cytochrome P450 superfamily encompasses a diverse group of enzymes that catalyze the oxidation of various substrates.


Input: The mouse CYP2J subfamily includes members that have wide tissue distribution and are active in the metabolism of arachidonic acid (AA), linoleic acid (LA), and other lipids and xenobiotics.

arachidonic acid

linoleic acid


Input: The mouse Cyp2j locus contains seven genes and three pseudogenes located in a contiguous 0. 62 megabase cluster on chromosome 4.


Input: We describe four new mouse CYP2J isoforms (designated CYP2J8, CYP2J11, CYP2J12, and CYP2J13).


Input: The four cDNAs contain open reading frames that encode polypeptides with 62-84% identity with the three previously identified mouse CYP2Js.


Input: All four new CYP2J proteins were expressed in Sf21 insect cells.


Input: Each recombinant protein metabolized AA and LA to epoxides and hydroxy derivatives.

epoxides

hydroxy


Input: Specific antibodies, mRNA probes, and polymerase chain reaction primer sets were developed for each mouse CYP2J to examine their tissue distribution.


Input: CYP2J8 transcripts were found in the kidney, liver, and brain, and protein expression was confirmed in the kidney and brain (neuropil).


Input: CYP2J11 transcripts were most abundant in the kidney and heart, with protein detected primarily in the kidney (proximal convoluted tubules), liver, and heart (cardiomyocytes).


Input: CYP2J12 transcripts were prominently present in the brain, and CYP2J13 transcripts were detected in multiple tissues, with the highest expression in the kidney.


Input: CYP2J12 and CYP2J13 protein expression could not be determined because the antibodies developed were not immunospecific.


Input: We conclude that the four new CYP2J isoforms might be involved in the metabolism of AA and LA to bioactive lipids in mouse hepatic and extrahepatic tissues.


Input: An Anti-angiogenic Reverse Thermal Gel as a Drug-Delivery System for Age-Related Wet Macular Degeneration.


Input: Reverse thermal gels have numerous biomedical implications, as they undergo physical gelation upon temperature increases and can incorporate biomolecules to promote tissue repair.


Input: Such a material is developed for the sustained release of bevacizumab (Avastin), a drug used to treat age-related macular degeneration.


Input: The polymer, poly (ethylene glycol)-poly (serinol hexamethylene urethane) (ESHU), forms a physical gel when heated to 37 degrees C and shows good cytocompatibility with ocular cells.

poly (ethylene glycol)-poly (serinol hexamethylene urethane)

ESHU


Input: ESHU is capable of sustaining bevacizumab release over 17 weeks in vitro, and the release kinetics can be altered by changing the drug dose and the ESHU concentration.

ESHU

ESHU


Input: These results suggest that ESHU is biologically safe, and suitable for ocular drug delivery.

ESHU


Input: Innovation and originality in the strategies developed by bacteria to get access to iron.

iron


Input: Pumping iron: Raymond' s group has identified and described the molecular details of an ABC transporter.


Input: Together with a binding protein at the cell surface, it is able to extract an unstable form of ferricitrate.


Input: Structure and dynamic regulation of Abl kinases.


Input: The c-abl proto-oncogene encodes a unique protein-tyrosine kinase (Abl) distinct from c-Src, c-Fes, and other cytoplasmic tyrosine kinases.

tyrosine

tyrosine


Input: In normal cells, Abl plays prominent roles in cellular responses to genotoxic stress as well as in the regulation of the actin cytoskeleton.


Input: Abl is also well known in the context of Bcr-Abl, the oncogenic fusion protein characteristic of chronic myelogenous leukemia.


Input: Selective inhibitors of Bcr-Abl, of which imatinib is the prototype, have had a tremendous impact on clinical outcomes in chronic myelogenous leukemia and revolutionized the field of targeted cancer therapy.

imatinib


Input: In this minireview, we focus on the structural organization and dynamics of Abl kinases and how these features influence inhibitor sensitivity.


Input: Extraction of essential oil from Cupressus sempervirens: comparison of global yields, chemical composition and antioxidant activity obtained by hydrodistillation and supercritical extraction (+).


Input: In this study, supercritical fluid extraction (SFE) with CO (2) and hydrodistillation (HD) were compared as methods to isolate the essential oil from Cupressus sempervirens.

CO (2)


Input: The odour of the oil obtained by SFE at 90 bar and 40 degrees C was very close to the odour of the leaves of C. sempervirens before the extraction.


Input: Compounds extracted by both SFE and HD were identified by GC-FID and GC-MS.


Input: Moreover, the difference in the chemical composition obtained by SFE and HD was quite noticeable qualitatively and quantitatively.


Input: Phenolic composition and antioxidant activity were also determined.


Input: Compared to HD, the SFE method presents some advantages: the extraction was completed after 1 h in SFE, although 4 h is necessary for HD, and the yield was improved by 34%.


Input: Finally, it has also been shown that SFE is very selective towards some specific components such as manoyl oxide, trans-totarol and alpha-acoradiene.

manoyl oxide

trans-totarol

alpha-acoradiene


Input: Targeting adenosine signaling to treatment of diabetic nephropathy.

adenosine


Input: Diabetic nephropathy (DN) continues being the primary cause of chronic hemodialysis and terminal renal disease worldwide.


Input: At tissue levels the DN occurs with glomerulopathy affecting the integrity of the filtration barrier and with an extensive glomerular and tubule-interstitial fibrosis.


Input: Current available therapeutic approaches have only demonstrated a modest effect on progression of kidney injury.


Input: Therefore, more research concerning the pathomechanisms and possible interventions are needed.


Input: Interestingly, in the last years it has been documented that DN progresses with growing levels of the nucleoside adenosine.

adenosine


Input: This finding increased the interest in the events controlling the extracellular levels of the nucleoside.

nucleoside


Input: While the metabolism of extracellular ATP and cyclic AMP are well recognized sources, evidences regarding the role of the equilibrative nucleoside transporters in controlling adenosine availability and promoting diabetic glomerulopathy have recently acquired a pivotal role.

ATP

cyclic AMP

nucleoside

adenosine


Input: The physiological effects of nucleoside are mediated by the P1 family of adenosine receptors.

nucleoside

adenosine


Input: It has been shown in vivo that the use of an antagonist of the A2B receptor subtype can block the most remarkable early alterations seen in diabetic glomerulopathy.


Input: Furthermore, using models of chronic kidney injury it was demonstrated that fibrosis can also be blocked using treatment with the antagonist of A2B receptor subtype.


Input: This review highlights these findings that correlate the activity of a low affinity adenosine receptor with an increase in the ligand availability in the pathological state.

adenosine


Input: In addition, we discuss the possible therapeutic interventions of adenosine signaling with regards to DN treatment.

adenosine


Input: Matrix metalloproteinases as potential targets in the venous dilation associated with varicose veins.


Input: Varicose veins (VVs) are a common venous disease of the lower extremity characterized by incompetent valves, venous reflux, and dilated and tortuous veins.


Input: If untreated, VVs could lead to venous thrombosis, thrombophlebitis and chronic venous leg ulcers.


Input: Various genetic, hormonal and environmental factors may lead to structural changes in the vein valves and make them incompetent, leading to venous reflux, increased venous pressure and vein wall dilation.


Input: Prolonged increases in venous pressure and vein wall tension are thought to increase the expression/activity of matrix metalloproteinases (MMPs).


Input: Members of the MMPs family include collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs and others.


Input: MMPs are known to degrade various components of the extracellular matrix (ECM).


Input: MMPs may also affect the endothelium and vascular smooth muscle, causing changes in the vein relaxation and contraction mechanisms.


Input: Endothelial cell injury also triggers leukocyte infiltration, activation and inflammation, which lead to further vein wall damage.


Input: The vein wall dilation and valve dysfunction, and the MMP activation and superimposed inflammation and fibrosis would lead to progressive venous dilation and VVs formation.


Input: Surgical ablation is an effective treatment for VVs, but may be associated with high recurrence rate, and other less invasive approaches that target the cause of the disease are needed.


Input: MMP inhibitors including endogenous tissue inhibitors (TIMPs) and pharmacological inhibitors such as zinc chelators, doxycycline, batimastat and marimastat, have been used as diagnostic and therapeutic tools in cancer, autoimmune and cardiovascular disease.

zinc

doxycycline

batimastat

marimastat


Input: However, MMP inhibitors may have side effects especially on the musculoskeletal system.


Input: With the advent of new genetic and pharmacological tools, specific MMP inhibitors with fewer undesirable effects could be useful to retard the progression and prevent the recurrence of VVs.


Input: Solphenazines A-F, glycosylated phenazines from Streptomyces sp. strain DL-93.

Solphenazines A-F

glycosylated phenazines


Input: During a survey of actinobacteria known to suppress the growth of Streptomyces scabies (the causative agent of potato scab disease) in vivo, six new rhamnosylated alkaloids, the solphenazines A-F (1-6), were isolated from a biological control strain of Streptomyces (DL-93).

solphenazines A-F


Input: The known rhamnosyl analogue of paraben (9) was also isolated along with a new rhamnosylated derivative of N-methyl-p-aminobenzoic acid (10).

rhamnosyl

paraben

N-methyl-p-aminobenzoic acid


Input: None of the compounds exhibited any antibacterial or antifungal activity against a standard panel of microorganisms, but compounds 1, 2, and 6 displayed some cytotoxicity against HCT-116 cancer cells.


Input: Additional in vitro testing provided data suggesting that the cytotoxic activity is not due to DNA intercalation or topoisomerase inhibition.


Input: Synthesis and biological evaluation as microtubule-active agents of several tetrahydrofuran and spiroacetal derivatives.

tetrahydrofuran

spiroacetal


Input: The stereoselective preparation of several molecules containing structural fragments of the tetrahydrofuran and spiroacetal type is described.

tetrahydrofuran

spiroacetal


Input: Their degree of cytotoxicity and their interactions with tubulin have been investigated.


Input: It has been confirmed that the tetrahydrofuran derivatives are cytotoxic but, in contrast to previous reports, it has been found that the cytoxicity is not due to interactions with the microtubule network.

tetrahydrofuran


Input: Furthermore, and also in contrast to a previous report on closely related compounds, the spiroacetal derivatives do show interactions with tubulin, even though the precise mechanism and the binding site still remain to be established.

spiroacetal


Input: The oxygen therapy.

oxygen


Input: Oxygen (O (2)) is a vital element.

Oxygen

O (2)


Input: Shortage of O (2) results in deranged metabolism and important changes in vascular tone with opposite effects on the systemic and pulmonary circulation.

O (2)


Input: During hypoxemia, oxidative stress exposes the organism to a sort of accelerated senescence as well as to several acute untoward effects.


Input: Thus, hypoxemia should be promptly recognized and treated, hopefully by measures tailored to the pathophysiological mechanisms underlying hypoxemia.


Input: However, O (2) therapy remains the most common therapy of hypoxemia, but it must be carefully tailored to relieve hypoxemia without provoking hyperoxia or hypercarbia.

O (2)


Input: Then, the individual response to O (2) as well as changing needs of O (2) during sleep or exercise must be evaluated to provide the best O (2) therapy.

O (2)

O (2)

O (2)


Input: Hyperoxia, the effect of overcorrection of hypoxia, can dramatically impact the health status and threaten the survival of the newborn and, through different mechanisms and effects, the adult.


Input: A thorough knowledge of the pathophysiological bases of hypoxemia and O (2) storage and delivery devices is then mandatory to administer O (2) therapy guaranteeing for optimal correction of hypoxemia and minimizing the risk of hyperoxia.

O (2)

O (2)


Input: Consistent with this aim also is a careful scrutiny of instruments and procedures for monitoring the individual response to O (2) over time.

O (2)


Input: Thus, at variance from classical pharmacological therapy, performing O (2) therapy requires a vast array of clinical and technical competences.

O (2)


Input: The optimal integration of these competences is needed to optimize O (2) therapy on individual bases.

O (2)


Input: Recent Developments of p38 alpha MAP Kinase Inhibitors as Antiinflammatory Agents Based on the Imidazole Scaffolds.

Imidazole


Input: Rheumatoid arthritis (RA) and other chronic inflammatory diseases are always the major therapeutic challenges.


Input: Recent research efforts provided new insights into the molecular basis of these diseases and new opportunities for developing improved anti-inflammatory drugs.


Input: The p38 mitogen-activated protein (MAP) kinase plays a central role in the regulation of the biosynthesis and release of several proinflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta).


Input: Hence, inhibition of the p38 MAP kinase is regarded as a promising therapeutic strategy for controlling inflammatory diseases.


Input: A diverse range of p38 alpha MAP kinase inhibitors have been developed as potential anti-inflammatory agents, and some of them have entered the phase II clinical trials.


Input: The imidazole derivatives are known as competitive inhibitors at the ATP binding site of the p38 alpha MAP kinase.

imidazole

ATP


Input: Modifications on the imidazole scaffold have led to a large amount of potent p38 alpha MAP kinase inhibitors.

imidazole


Input: This review will summarize the developments of small molecule p38 alpha MAP kinase inhibitors based on the imidazole core scaffolds in recent 10 years.

imidazole


Input: Variations at the N1, C2, C4 and C5 positions of imidazole were introduced, and the structure-activity relationships of these imidazole inhibitors were also discussed.

imidazole

imidazole


Input: What happens to the thiolates created by reductively desorbing SAMs?

thiolates


Input: An in situ study using fluorescence microscopy and electrochemistry.


Input: In situ examination of the reductive desorption process for Au microelectrodes modified with a thiol self-assembled monolayer (SAM) using fluorescence microscopy enabled the study of the fate of the desorbed thiolate species.

Au

thiol

thiolate


Input: The Bodipy labeled alkyl-thiol SAM, when adsorbed, is not fluorescent due to quenching by the Au surface.

thiol

Au


Input: Once reductively desorbed, the thiolate molecules fluoresce and their direction and speed are monitored.

thiolate


Input: At moderately negative reduction potentials, the thiolate species hemispherically diffuse away from the microelectrode.

thiolate


Input: Also observed is the influence of a closely positioned counter electrode on the direction of the desorbed thiolate movement.

thiolate


Input: As the potential becomes more negative, the molecules move in an upward direction, with a speed that depends on the amount of dissolved H (2) produced by water reduction.

H (2)


Input: Shown is that this motion is controlled, in large part, by the change in the electrolyte density near the electrode due to dissolved H (2).

H (2)


Input: These results should help in explaining the extent of readsorption at oxidative potentials observed in cyclic voltammetry (CV) reductive desorption measurements, as well as improving the general understanding of the SAM removal process by reductive desorption.


Input: The electrogenerated H (2) was also shown to be able to reductively remove the thiol SAM from the Pt/Ir particles that decorate the microelectrode glass sheath.

H (2)

Pt

Ir


Input: Lead optimization of a pyridine-carboxamide series as DGAT-1 inhibitors.

pyridine-carboxamide


Input: The structure-activity relationship studies of a novel series of carboxylic acid derivatives of pyridine-carboxamides as DGAT-1 inhibitors is described.

carboxylic acid

pyridine-carboxamides


Input: The optimization of the initial lead compound 6 based on in vitro and in vivo activity led to the discovery of key compounds 10j and 17h.


Input: Atomic pair distribution functions analysis of disordered low-Z materials.


Input: Results of high-energy X-ray diffraction experiments coupled to atomic pair distribution function analysis of disordered low-Z materials are presented.


Input: Several scientifically and technologically important classes of disordered low-Z materials such as small and large organic molecules, graphitic powders, polymers and liquids are intentionally explored to certify the technique' s performance.

graphitic


Input: Results clearly show that disordered low-Z materials can be well characterized in terms of material' s phase identity, relative abundance in mixtures and atomic-scale structure.


Input: The demonstrated efficiency of the technique provides the scientific community with much needed confidence to apply it more often than now.


Input: ErbB2, FoxM1 and 14-3-3 zeta prime breast cancer cells for invasion in response to ionizing radiation.


Input: ErbB2 is frequently highly expressed in premalignant breast cancers, including ductal carcinoma in situ (DCIS); however, little is known about the signals or pathways it contributes to progression into the invasive/malignant state.


Input: Radiotherapy is often used to treat early premalignant lesions regardless of ErbB2 status.


Input: Here, we show that clinically relevant doses of ionizing radiation (IR)-induce cellular invasion of ErbB2-expressing breast cancer cells, as well as MCF10A cells overexpressing ErbB2.


Input: ErbB2-negative breast cancer cells, such as MCF7 and T47D, do not invade following treatment with IR nor do MCF10A cells overexpressing epidermal growth factor receptor.


Input: ErbB2 becomes phosphorylated at tyrosine 877 in a dose-and time-dependent manner following exposure to X-rays, and activates downstream signaling cascades including PI3K/Akt.

tyrosine


Input: Inhibition of these pathways, as well as inhibition of reactive oxygen species (ROS) with antioxidants, prevents IR-induced invasion.

oxygen


Input: Activation of ErbB2-dependent signaling results in upregulation of the forkhead family transcription factor, FoxM1, and its transcriptional targets, including matrix metalloproteinase 2 (MMP2).


Input: Inhibition of FoxM1 by RNA interference prevented induction of invasion by IR, and overexpression of FoxM1 in MCF10A cells was sufficient to promote IR-induced invasion.


Input: Moreover, we found that 14-3-3 zeta is also upregulated by IR in cancer cells in a ROS-dependent manner, is required for IR-induced invasion in ErbB2-positive breast cancer cells and together with FoxM1 is sufficient for invasion in ErbB2-negative breast cancer cells.


Input: Thus, our data show that IR-mediated activation of ErbB2 and induction of 14-3-3 zeta collaborate to regulate FoxM1 and promote invasion of breast cancer cells and furthermore, may serve as therapeutic targets to enhance radiosensitivity of breast cancers. Oncogene advance online publication, 14 January 2013; doi: 10. 1038/onc. 2012. 629.


Input: TRIM3, a tumor suppressor linked to regulation of p21 (Waf1/Cip1).


Input: The TRIM family of genes is largely studied because of their roles in development, differentiation and host cell antiviral defenses; however, roles in cancer biology are emerging.


Input: Loss of heterozygosity of the TRIM3 locus in ~ 20% of human glioblastomas raised the possibility that this NHL-domain containing member of the TRIM gene family might be a mammalian tumor suppressor.


Input: Consistent with this, reducing TRIM3 expression increased the incidence of and accelerated the development of platelet-derived growth factor-induced glioma in mice.


Input: Furthermore, TRIM3 can bind to the cdk inhibitor p21 (WAF1/CIP1).


Input: Thus, we conclude that TRIM3 is a tumor suppressor mapping to chromosome 11p15. 5 and that it might block tumor growth by sequestering p21 and preventing it from facilitating the accumulation of cyclin D1-cdk4. Oncogene advance online publication, 14 January 2013; doi: 10. 1038/onc. 2012. 596.


Input: Effects of celiac superior mesenteric ganglionectomy on glucose homeostasis and hormonal changes during oral glucose tolerance testing in rats.

glucose

glucose


Input: The liver plays an important role in maintaining glucose homeostasis in the body.

glucose


Input: In the prandial state, some of the glucose which is absorbed by the gastrointestinal tract is converted into glycogen and stored in the liver.

glucose


Input: In contrast, the liver produces glucose by glycogenolysis and gluconeogenesis while fasting.

glucose


Input: Thus, the liver contributes to maintaining blood glucose level within normoglycemic range.

glucose


Input: Glycogenesis and glycogenolysis are regulated by various mechanisms including hormones, the sympathetic and parasympathetic nervous systems and the hepatic glucose content.

glucose


Input: In this study, we examined a rat model in which the celiac superior mesenteric ganglion (CSMG) was resected.


Input: We attempted to elucidate how the celiac sympathetic nervous system is involved in regulating glucose homeostasis by assessing the effects of CSMG resection on glucose excursion during an oral glucose tolerance test, and by examining hepatic glycogen content and hepatic glycogen phosphorylase (GP) activity.

glucose

glucose

glucose


Input: On the oral glucose tolerance test, CSMG-resected rats demonstrated improved glucose tolerance and significantly increased GP activity compared with sham-operated rats, whereas there were no significant differences in insulin, glucagon or catecholamine levels between the 2 groups.

glucose

glucose

catecholamine


Input: These results suggest that the celiac sympathetic nervous system is involved in regulating the rate of glycogen consumption through GP activity.


Input: In conclusion, the examined rat model showed that the celiac sympathetic nervous system regulates hepatic glucose metabolism in conjunction with vagal nerve innervations and is a critical component in the maintenance of blood glucose homeostasis.

glucose

glucose


Input: Butein protects human dental pulp cells from hydrogen peroxide-induced oxidative toxicity via Nrf2 pathway-dependent heme oxygenase-1 expressions.

Butein

hydrogen peroxide


Input: Rhus verniciflua Stokes is a plant that is native to East Asian countries, such as Korea, China, and Japan.


Input: Butein, a plant polyphenol, is one of the major active components of R. verniciflua.

Butein

polyphenol


Input: Reactive oxygen species (ROS), produced via dental adhesive bleaching agents and pulpal disease, can cause oxidative stress.

oxygen


Input: Here, we found that butein possesses cytoprotective effects on hydrogen peroxide (H2O2)-induced dental cell death.

butein

hydrogen peroxide


Input: H2O2 is a representative ROS and causes cell death through necrosis in human dental pulp (HDP) cells.


Input: H2O2-induced cytotoxicity and production of ROS were blocked in the presence of butein, and these effects were dose dependent.

butein


Input: Butein also increased heme oxygenase-1 (HO-1) protein expression and HO activity.

Butein

heme


Input: In addition, butein-dependent HO-1 expression was required for the inhibition of H2O2-induced cell death and ROS generation.

butein


Input: Furthermore, butein treatment caused nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements (AREs).

butein


Input: Treatment of HDP cells with a c-Jun NH2-terminal kinase (JNK) inhibitor also reduced butein-induced HO-1 expression, and butein treatment led to increased JNK phosphorylation.

butein

butein


Input: These results indicate that butein may be used to prevent functional dental cell death and thus may be useful as a pulpal disease agent.

butein


Input: Oxidative and nitrosative stress and apoptosis in oral mucosa cells after ex vivo exposure to lead and benzo [a] pyrene.

benzo [a] pyrene


Input: Exposure of human oral mucosa to lead (Pb) and benzo [a] pyrene (BaP) by inhalation and ingestion can lead to pathological conditions via apoptosis and oxidative and nitrosative stress.

Pb

benzo [a] pyrene

BaP


Input: However, few studies have investigated the effects of Pb and BaP on oral mucosa cells.

Pb

BaP


Input: Furthermore, previous studies focused on chronic Pb and BaP exposure.

Pb

BaP


Input: Therefore, we evaluated important markers of apoptosis and oxidative and nitrosative stress in oral mucosa cells by incubating the cells with Pb and BaP for 5-360 min.

Pb

BaP


Input: Ex vivo samples of human oral mucosa were exposed to Pb or BaP, and immunohistochemical staining was performed to evaluate active caspase-3, 8-epi-prostaglandin F2 alpha (8-epi-PGF2a), and 3-nitrotyrosine (3-NT).

Pb

BaP

8-epi-prostaglandin F2 alpha


Input: Pb and BaP treatments significantly increased active caspase-3 levels in a time-dependent manner.

Pb

BaP


Input: Furthermore, the treatments induced an early increase in 3-NT level, which ceased with longer incubation times.


Input: 8-Epi-PGF2a level increased only after prolonged incubation with Pb, and this elevation was irrespective of BaP incubation duration.

Pb

BaP


Input: Smokers' samples had significantly lower levels of markers of oxidative and nitrosative stress than did nonsmokers' samples.


Input: Thus, single, short-term exposure to Pb or BaP increases the levels of apoptosis markers and markers of oxidative and nitrosative stress.

Pb

BaP


Input: GC-MS analysis of Eucalyptus citriodora leaf extract and its role on the dietary supplementation in transgenic Drosophila model of Parkinson' s disease.


Input: The role of Eucalyptus citriodora L. leaf extract was studied on the transgenic Drosophila model of flies expressing normal human alpha synuclein (h-alpha S) in the neurons.


Input: These flies exhibit locomotor dysfunction as the age progresses.


Input: The leaf extract was prepared in acetone and was subjected to GC-MS analysis.


Input: The GC-MS analysis revealed the presence of nine major compounds.


Input: E. citriodora extract at final concentration of 0. 25, 0. 50 and 1. 0 mu l/ml was supplemented with the diet and the flies were allowed to feed for 21days.


Input: The effect of extract was studied on the climbing ability and the oxidative stress on the PD model Drosophila expressing normal human alpha synuclein (h-alpha S) in the neurons.


Input: The supplementation of 0. 25, 0. 50 and 1. 0 mu l/ml of E. citriodora extract showed a dose dependent significant delay in the loss of climbing ability and reduction in the oxidative stress in the brain of PD model flies.


Input: The results also support the utility of this model in studying PD symptoms.


Input: Effect of enzymatically modified isoquercitrin on preneoplastic liver cell lesions induced by thioacetamide promotion in a two-stage hepatocarcinogenesis model using rats.

isoquercitrin

thioacetamide


Input: To investigate the protective effect of enzymatically modified isoquercitrin (EMIQ) on the hepatocarcinogenic process, we used a two-stage hepatocarcinogenesis model in N-diethylnitrosamine-initiated and thioacetamide (TAA)-promoted rats.

isoquercitrin

N-diethylnitrosamine

thioacetamide

TAA


Input: We examined the modifying effect of co-administration with EMIQ on the liver tissue environment including hepatic macrophages and lymphocytes and on the induction mechanism of preneoplastic cell apoptosis during early stages of hepatocellular tumor promotion.


Input: TAA increased the number and area of glutathione S-transferase placental form (GST-P) (+) liver cell foci and the numbers of proliferating and apoptotic cells in randomly selected areas in liver sections.

TAA

glutathione S


Input: Co-administration with EMIQ suppressed these effects.


Input: TAA also increased the numbers of ED2 (+), cyclooxygenase-2 (+), and heme oxygenase-1 (+) liver cells, as well as the number of CD3 (+) lymphocytes.

TAA

heme


Input: These effects were also suppressed by EMIQ.


Input: EMIQ increased liver levels of thiobarbituric acid-reactive substance and 8-hydroxydeoxyguanosine, and TUNEL (+) apoptotic cells, death receptor 5 (DR5) (+) cells and 4-hydroxy-2-nonenal (+) cells within GST-P (+) foci.

thiobarbituric acid


Input: Outside the GST-P (+) foci, EMIQ decreased the numbers of apoptotic cells and DR5 (+) cells.


Input: These results suggest that TAA-induced tumor promotion involves activation of hepatic macrophages producing proinflammatory factors.

TAA


Input: EMIQ may suppress the TAA-induced tumor-promoting activity by an anti-inflammatory mechanism mediated by suppressing the activation of these macrophages.

TAA


Input: Furthermore, EMIQ may suppress tumor-promoting activity differentially between the inside and outside of GST-P (+) foci.


Input: Within GST-P (+) foci, EMIQ facilitates the apoptosis of preneoplastic cells through the upregulation of DR5.


Input: Outside the GST-P (+) foci, EMIQ suppresses apoptosis and the subsequent regeneration of non-transformed liver cells.


Input: Bioavailability and intravenous toxicokinetic parameters for Pacific ciguatoxin P-CTX-1 in rats.

ciguatoxin


Input: Ciguatoxins are sodium channel activator toxins responsible for ciguatera fish poisoning.

Ciguatoxins

sodium


Input: In this study, we determined the toxicokinetic parameters of the Pacific ciguatoxin P-CTX-1 in rats after an intravenous (iv) dose of 0. 13 ng P-CTX-1 per g of body weight.

ciguatoxin


Input: The ciguatoxin activity was assessed over time in blood using the sensitive functional Neuro2a assay.

ciguatoxin


Input: The data were analyzed with a two-compartmental model.


Input: After exposure, the ciguatoxin activity exhibited a rapid (alpha half-life of 6 min) and extensive distribution into tissues (apparent steady state volume of distribution of 7. 8 L).

ciguatoxin


Input: Ciguatoxin elimination from blood was slower with a beta half-life estimated at 35. 5 h.

Ciguatoxin


Input: The toxicokinetic parameters determined from this study were compared to data previously obtained after oral and intraperitoneal exposure of rats to 0. 26 ng P-CTX-1 per g of body weight.


Input: Maximal bioavailability was determined by the area under the concentration curve, and was used to calculate the absolute P-CTX-1 bioavailabilities for oral and intraperitoneal routes of exposures of 39% and 75%, respectively.


Input: Identification of alpha 2 beta 1 integrin inhibitor VP-i with anti-platelet properties in the venom of Vipera palaestinae.


Input: Integrins are receptors of the extracellular matrix (ECM), playing a vital role in pathophysiological processes.


Input: They bind to ECM ligands like collagens and can mediate wound healing as well as tumor metastasis and thrombosis, thus being a part of cell adhesion and migration as well as platelet aggregation.


Input: For this reason, identifying alpha 2 beta 1 integrin-specific antagonists can assist in the development of drugs to treat tumor progression, angiogenesis, and cardiovascular diseases.


Input: Snake venoms have been shown to contain antagonists which target collagen-binding integrins.


Input: EMS16, rhodocetin, and VP12 are three toxins belonging to the C-type lectin-related protein family and have been proven to inhibit the alpha 2 beta 1 integrin, specifically the alpha 2 integrin A domain.


Input: To specifically isolate antagonists targeting the alpha 2 beta 1 integrin A domain, we developed a protocol based on affinity chromatography.


Input: Using this novel approach, the toxin VP-i was isolated from Vipera palaestinae venom.


Input: We show that VP-i binds to the alpha 2 integrin A domain and that it successfully inhibits adhesion of various cells to type I collagen as well as cell migration.


Input: Moreover, our results indicate that VP-i differs structurally from the previously purified VP12, although not functionally, and therefore is a further venom compound which can be utilized for drug development.


Input: Mechanical characteristics of human red blood cell membrane change due to C60 nanoparticle infiltration.


Input: The mechanical characteristics of human red blood cell (RBC) membrane change due to C (60) nanoparticle (NP) infiltration have been investigated in the present work.

C (60)


Input: Using experimental approaches, including optical tweezer (OT) stretching and atomic force microscopy (AFM) indentation, we found that RBCs in the presence of C (60) NPs are softer than normal RBCs.

C (60)


Input: The strain-stress relations of both normal and C (60) infiltrated RBC membranes are extracted from the data of AFM indentation, from which we proved that C (60) NP infiltration can affect the mechanical properties of RBC membrane and tend to weaken the tensile resistance of lipids bilayers.

C (60)

C (60)


Input: In order to explain this experimental phenomenon, a mechanical model has been developed.


Input: Based on this model, the strain-stress relations of both normal and C (60) infiltrated lipid bilayers are calculated with consideration of intermolecular interactions.

C (60)


Input: The theoretical results are in great agreement with the experimental results.


Input: The influence of C (60) NP concentration on the mechanical properties of RBC membrane is successfully predicted.

C (60)


Input: Higher concentrations of C (60) NPs in the lipid bilayers will lead to increased damage to the cell membrane, implying that the dosage of C (60) NPs should be controlled in medical applications.

C (60)

C (60)


Input: Steady and out-of-equilibrium phase diagram of a complex fluid at the nanolitre scale: combining microevaporation, confocal Raman imaging and small angle X-ray scattering.


Input: We engineered specific microfluidic devices based on the pervaporation of water through a PDMS membrane, to formulate continuous and steady concentration gradients of a binary aqueous molecular mixture at the nanolitre scale.

PDMS


Input: In the case of a model complex fluid (a triblock copolymer solution), we demonstrate that such a steady gradient crosses the phase diagram from pure water up to a succession of highly viscous mesophases.


Input: We then performed in situ spatially resolved measurements (confocal spectroscopy and small-angle X-ray scattering) to quantitatively measure the concentration profile and to determine the microstructure of the different textures.


Input: Within a single microfluidic channel, we thus screen quantitatively and continuously the phase diagram of a complex fluid.


Input: Beside, as such a gradient corresponds to an out-of-equilibrium regime, we also extract from the concentration measurement a precise estimate of the collective diffusion coefficient of the mixture as a function of the concentration.


Input: In the present case of the triblock copolymer, this transport coefficient features discontinuities at some phase boundaries, which have never been observed before.


Input: An N-terminal nuclear export signal regulates trafficking and aggregation of Huntingtin (Htt) protein exon 1.

N


Input: Huntington disease is a dominantly inherited neurodegenerative condition caused by polyglutamine expansion in the N terminus of the huntingtin protein (Htt).

polyglutamine

N


Input: The first 17 amino acids (N17) of Htt play a key role in regulating its toxicity and aggregation.

amino acids


Input: Both nuclear export and cytoplasm retention functions have been ascribed to N17.


Input: We have determined that N17 acts as a nuclear export sequence (NES) within Htt exon and when fused to yellow fluorescent protein.


Input: We have defined amino acids within N17 that constitute the nuclear export sequence (NES).

amino acids


Input: Mutation of any of the conserved residues increases nuclear accumulation of Htt exon 1.


Input: Nuclear export of Htt is sensitive to leptomycin B and is reduced by knockdown of exportin 1.

leptomycin B


Input: In HEK293 cells, NES mutations decrease overall Htt aggregation but increase the fraction of cells with nuclear inclusions.


Input: In primary cultured neurons, NES mutations increase nuclear accumulation and increase overall aggregation.


Input: This work defines a bona fide nuclear export sequence within N17 and links it to effects on protein aggregation.


Input: This may help explain the important role of N17 in controlling Htt toxicity.


Input: Single-molecule catalysis mapping quantifies site-specific activity and uncovers radial activity gradient on single 2D nanocrystals.


Input: Shape-controlled metal nanocrystals are a new generation of nanoscale catalysts.