Input: In contrast tasocitinib, a predominantly JAK3 inhibitor, is being evaluated in a number of inflammatory and immunological diseases, including rheumatoid arthritis, psoriasis, ulcerative colitis, dry eye disease and in kidney transplant patients.

tasocitinib


Input: In conclusion the use of JAK inhibitors in MPN and some of the immune-mediated disorders is a promising new strategy for therapy.


Input: However, definitive data from ongoing and future preclinical and clinical trials will aid in better defining the status of these drugs in the treatment of these diseases.


Input: Cellular signaling crosstalk between multiple receptors for investigation of pathophysiology in multifactorial diseases--what is clinically-relevant crosstalk?


Input: Recently, genomics and proteomics have been utilized as advanced tools for investigation of cellular signaling pathways and molecular interactions, and elucidated promiscuous networks composed of numerous interactions among pathways.


Input: However, some of these interactions are considered to be simply contributing to background' noise' and others are as' crosstalk' biologically-relevant to cellular physiology, leading to synergy effects more than additive responses in an entire organism.


Input: Effort is now required to determine which interactions truly contribute to final physiological output.


Input: A receptor is the prime example of connectors among the networks.


Input: It functions, not simply as a signaling gateway, but also as an active trader by forming inter-receptor dimers.


Input: Furthermore, various receptors can modulate the function of the other receptors by input to common intracellular signaling pathways, establishing functional crosstalk among networks.


Input: Our findings by combined analyses of gene polymorphisms of two separate genes present evidences that such is the case with human body in a clinical setting: 1) an integrated effect of epidermal growth factor receptor (EGFR) and protease activated receptor-1 (PAR-1) on susceptibility to airway hyperresponsiveness (AHR), and 2) a crosstalk effect between muscarinic acetylcholine receptor (mAChRs) and beta (2) adrenoceptor (beta (2) AR) on bronchodilatory response to anticholinergic agents in patients with COPD.

acetylcholine


Input: These results indicate that these interactions are unlikely to be' noise' but functionally-relevant' crosstalk' in a human body.


Input: This review attempts to highlight the clinically-relevant' crosstalk' paradigm in a human body which provides us a novel insight necessary to investigate pathophysiology in common multifactorial diseases and to develop new drugs.


Input: Mechanism of copper (I)/TEMPO-catalyzed aerobic alcohol oxidation.

copper (I)

alcohol


Input: Homogeneous Cu/TEMPO catalyst systems (TEMPO = 2, 2, 6, 6-tetramethylpiperidine-N-oxyl) have emerged as some of the most versatile and practical catalysts for aerobic alcohol oxidation.

Cu

TEMPO

TEMPO

2, 2, 6, 6-tetramethylpiperidine-N-oxyl

alcohol


Input: Recently, we disclosed a (bpy) Cu (I)/TEMPO/NMI catalyst system (NMI = N-methylimidazole) that exhibits fast rates and high selectivities, even with unactivated aliphatic alcohols.

Cu (I)

TEMPO

NMI

NMI

N-methylimidazole

alcohols


Input: Here, we present a mechanistic investigation of this catalyst system, in which we compare the reactivity of benzylic and aliphatic alcohols.

benzylic and aliphatic alcohols


Input: This work includes analysis of catalytic rates by gas-uptake and in situ IR kinetic methods and characterization of the catalyst speciation during the reaction by EPR and UV-visible spectroscopic methods.


Input: The data support a two-stage catalytic mechanism consisting of (1) " catalyst oxidation " in which Cu (I) and TEMPO-H are oxidized by O (2) via a binuclear Cu (2) O (2) intermediate and (2) " substrate oxidation " mediated by Cu (II) and the nitroxyl radical of TEMPO via a Cu (II)-alkoxide intermediate.

Cu (I)

TEMPO

H

O (2)

Cu (2) O (2)

Cu (II)

nitroxyl

Cu (II)

alkoxide


Input: Catalytic rate laws, kinetic isotope effects, and spectroscopic data show that reactions of benzylic and aliphatic alcohols have different turnover-limiting steps.

benzylic and aliphatic alcohols


Input: Catalyst oxidation by O (2) is turnover limiting with benzylic alcohols, while numerous steps contribute to the turnover rate in the oxidation of aliphatic alcohols.

O (2)

benzylic alcohols

aliphatic alcohols


Input: Recent progress in biological activities and synthetic methodologies of pyrroloquinoxalines.

pyrroloquinoxalines


Input: Pyrroloquinoxalines have proved to be a very attractive scaffold for medicinal chemist in the recent past.

Pyrroloquinoxalines


Input: These compounds were extensively studied as bioactive compounds and many of them are known to be biologically and medicinally useful molecules, such as anti-HIV agents, antimalarial agents, antagonist agents, anticancer agents, and PARP-1 inhibitors.


Input: Additionally, pyrroloquinoxalines are also important intermediates for the construction of 5-HT3 receptor agonists.

pyrroloquinoxalines


Input: In this review the developments in biological activities and synthetic methodologies of pyrroloquinoxalines are discussed.

pyrroloquinoxalines


Input: Small-molecule inhibitors for the treatment of hepatitis B virus documented in patents.


Input: Hepatitis B virus (HBV) infection is a serious health problem worldwide, and the current treatment methods including vaccines, immunomodulators, interferons and nucleoside analogs are far from satisfactory.

nucleoside


Input: For the search of new anti-HBV agents, much investigation has revealed a large number of small-molecule compounds with various skeletons and promising anti-HBV activities.


Input: Although some reviews on anti-HBV progress have been published, they are mainly concentrated on the results reported in journal articles.


Input: This review provides an overview of the structural features and anti-HBV properties of the small-molecule anti-HBV inhibitors claimed in recent patents (from 2001 to 2010).


Input: These small-molecules can be structurally classified as two main types, nucleoside analogs (cyclic and acyclic nucleosides) and non-nucleosides (natural and synthesized compounds), which are declared with the activity inhibiting the secretion of HBsAg and HBeAg and HBV DNA replication in vitro, as well as anti-DHBV DNA in vivo.

nucleoside

nucleosides

nucleosides


Input: Especially, the non-nucleosides with diverse skeletons and novel mechanism offer prolific candidates for anti-HBV drug discovery, which are preferred to be used as adjuvant therapy for HBV infection.

nucleosides


Input: This paper will provide valuable information for understanding the current anti-HBV investigation and developing new anti-HBV agents.


Input: Radiolytic transformation of rotenone with potential anti-adipogenic activity.

rotenone


Input: Radiolytic transformation of the isoflavonoid rotenone (1) with gamma-irradiation afforded two new degraded products, rotenoisins A (2) and (3).

isoflavonoid rotenone

rotenoisins A


Input: The structures of the two new rotenone derivatives were elucidated on the basis of spectroscopic methods.

rotenone


Input: The new products 2 and 3 exhibited significantly enhanced inhibitory activities against pancreatic lipase and adipocyte differentiation in 3T3-L1 cells when compared to parent rotenone.

rotenone


Input: ATP stimulates PGE (2)/cyclin D1-dependent VSMCs proliferation via STAT3 activation: role of PKCs-dependent NADPH oxidase/ROS generation.

ATP

PGE (2)

NADPH


Input: Vascular smooth muscle cells (VSMCs) that function as synthetic units play important roles in cardiovascular diseases.


Input: Extracellular nucleotides, such as ATP, have been shown to act via activation of P2 purinoceptors implicated in various inflammatory diseases, we hypothesized that extracellular nucleotides contribute to vascular diseases via up-regulation of inflammatory proteins, including cyclooxygenase-2 (COX-2) and cytosolic phospholipase A2 (cPLA2) in VSMCs.

nucleotides

ATP

nucleotides


Input: However, the mechanisms of ATP-induced cPLA2 and COX-2 expression and PGE2 synthesis remain largely unclear.

ATP


Input: We showed that pretreatment with the inhibitors of STAT3 (CBE), NADPH oxidase [diphenyleneiodonium chloride (DPI) or apocynin (APO)], ROS [N-acetyl-l-cysteine (NAC)], and PKC (Ro-318220, G o 6983, or Rottlerin) or transfection with siRNAs of STAT3 and p47 (phox) markedly inhibited ATP gamma S-induced cPLA2 and COX-2 mRNA/protein expression and promoter activity and PGE2 secretion.

NADPH

diphenyleneiodonium chloride

DPI

apocynin

APO

N-acetyl-l-cysteine

NAC

G o 6983

Rottlerin


Input: ATP gamma S further stimulated PKC, p47 (phox), and STAT3 translocation.


Input: Moreover, ATP gamma S-induced STAT3 phosphorylation and translocation was inhibited by pretreatment with the inhibitors of PKC, NADPH oxidase, and ROS.

NADPH


Input: ATP gamma S enhanced NADPH oxidase activity and ROS generation in VSMCs, which were reduced by pretreatment with Ro-318220, G o 6983, or Rottlerin.

NADPH

G o 6983

Rottlerin


Input: Finally, we found that ATP gamma S significantly induced cyclin D1 expression and VSMCs proliferation, which were inhibited by pretreatment with NAC, APO, DPI, Ro-318220, G o 6983, Rottlerin, or CBE or transfection with siRNAs of COX-2 and cyclin D1.

NAC

APO

DPI

G o 6983

Rottlerin


Input: We also demonstrated that ATP gamma S induced cyclin D1 expression via a PGE2-dependent pathway.


Input: These results suggested that ATP gamma S-induced cPLA2/COX-2 expression and PGE2 secretion is mediated through a PKC/NADPH oxidase/ROS/STAT3-dependent pathway in VSMCs.

NADPH


Input: DMAP1 is an essential regulator of ATM activity and function.


Input: The hereditary autosomal recessive disease ataxia telangiectasia (A-T) is caused by mutation in the DNA damage kinase ATM.


Input: ATM' s main function is to orchestrate DNA repair, thereby maintaining genomic stability.


Input: ATM activity is increased in response to several stimuli, including ionising radiation (IR) and hypotonic stress.


Input: DNMT1-associated protein 1 (DMAP1) is a member of the TIP60-p400 histone acetyl transferase (HAT) complex, which acetylates histone H4 at lysine 16 (H4K16) to affect chromatin relaxation and modulate ATM activation.

acetyl

lysine


Input: Here we demonstrate that DMAP1 is required for both modes of ATM activation.


Input: Knockdown of DMAP1 impaired IR-induced ATM activation and consequently resulted in radiosensitivity and impaired the G2/M checkpoint.


Input: Moreover, DMAP1 was also required for efficient ATM signalling in response to hypotonic stress.


Input: Overexpression of DMAP1 increased IR-induced ATM substrate phosphorylation, suggesting that DMAP1 function is rate limiting for ATM signalling.


Input: DMAP1 associated with TIP60-dependent HAT activity, and depletion of DMAP1 reduced H4K16 acetylation in response to DNA damage.


Input: Treatment with histone deacetylase inhibitors rescued IR-induced ATM signalling in Dmap1-depleted cells.


Input: These results suggest that DMAP1 is a critical regulator of ATM activity and function. Oncogene advance online publication, 14 January 2013; doi: 10. 1038/onc. 2012. 597.


Input: Evidence of mitochondrial dysfunction and impaired ROS detoxifying machinery in Fanconi Anemia cells.


Input: Fanconi Anemia (FA) is a rare genetic disorder associated with a bone-marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents.


Input: Majority of the 15 FA genes and encoded proteins characterized so far are integrated into DNA repair pathways, however, other important functions cannot be excluded.


Input: FA cells are sensitive to oxidants, and accumulation of oxidized proteins has been characterized for several FA subgroups.


Input: Clinical phenotypes of both FA and other closely related diseases suggest altered functions of mitochondria, organelles responsible for cellular energetic metabolism, and also serving as an important producer and the most susceptible target from reactive oxidative species (ROS).


Input: In this study, we have shown that elevated level of mitochondrial ROS in FA cells is in parallel with the decrease of mitochondrial membrane potential, the decrease of ATP production, impaired oxygen uptake and pathological changes in the morphology of mitochondria.

oxygen


Input: This is accompanied by inactivation of enzymes that are essential for the energy production (F1F0ATPase and cytochrome C oxidase) and detoxification of ROS (superoxide dismutase, SOD1).

superoxide


Input: In turn, overexpression of SOD1 could rescue oxygen consumption rate in FA-deficient cells.

oxygen


Input: Importantly, the depletion of mitochondria improved survival rate of mitomycin C treated FA cells suggesting that hypersensitivity of FA cells to chemotherapeutic drugs could be in part due to the mitochondria-mediated oxidative stress.


Input: On the basis of our results, we propose that deficiency in FA genes lead to disabling mitochondrial ROS-scavenging machinery further affecting mitochondrial functions and suppressing cell respiration. Oncogene advance online publication, 14 January 2013; doi: 10. 1038/onc. 2012. 583.


Input: Axl/Gas6/NF kappa B signalling in schwannoma pathological proliferation, adhesion and survival.


Input: TAM family receptor tyrosine kinases comprising Tyro3 (Sky), Axl, and Mer are overexpressed in some cancers, correlate with multidrug resistance and contribute to tumourigenesis by regulating invasion, angiogenesis, cell survival and tumour growth.


Input: Mutations in the gene coding for a tumour suppressor merlin cause development of multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas occurring spontaneously or as part of a hereditary disease neurofibromatosis type 2.


Input: The benign character of merlin-deficient tumours makes them less responsive to chemotherapy.


Input: We previously showed that, amongst other growth factor receptors, TAM family receptors (Tyro3, Axl and Mer) are significantly overexpressed in schwannoma tissues.


Input: As Axl is negatively regulated by merlin and positively regulated by E3 ubiquitin ligase CRL4DCAF1, previously shown to be a key regulator in schwannoma growth we hypothesized that Axl is a good target to study in merlin-deficient tumours.


Input: Moreover, Axl positively regulates the oncogene Yes-associated protein, which is known to be under merlin regulation in schwannoma and is involved in increased proliferation of merlin-deficient meningioma and mesothelioma.


Input: Here, we demonstrated strong overexpression and activation of Axl receptor as well as its ligand Gas6 in human schwannoma primary cells compared to normal Schwann cells.


Input: We show that Gas6 is mitogenic and increases schwannoma cell-matrix adhesion and survival acting via Axl in schwannoma cells.


Input: Stimulation of the Gas6/Axl signalling pathway recruits Src, focal adhesion kinase (FAK) and NF kappa B.


Input: We showed that NF kappa B mediates Gas6/Axl-mediated overexpression of survivin, cyclin D1 and FAK, leading to enhanced survival, cell-matrix adhesion and proliferation of schwannoma.


Input: We conclude that Axl/FAK/Src/NF kappa B pathway is relevant in merlin-deficient tumours and is a potential therapeutic target for schwannoma and other merlin-deficient tumours. Oncogene advance online publication, 14 January 2013; doi: 10. 1038/onc. 2012. 587.


Input: The costimulatory molecule B7-H4 promote tumor progression and cell proliferation through translocating into nucleus.


Input: B7-H4, a member of B7 family, is a transmembrane protein and inhibits T-cells immunity.


Input: However, in a variety of tumor cells, B7-H4 was detected predominantly in intracellular compartments with unknown mechanism and functions.


Input: In this study, we analyzed B7-H4 expression and subcellular distribution by immunohistochemistry in renal cell carcinoma (RCC) tissues.


Input: B7-H4 protein was detected on the membrane, in the cytosol and/or in the nucleus in tumor tissues.


Input: The membrane and nuclear expression of B7-H4 was significantly correlated with the tumor stages of RCC.


Input: Moreover, the membrane localization of B7-H4 was inversely correlated with the intensity of tumor infiltrates lymphocyte (TILs), whereas no association was observed between nuclear expression of B7-H4 and the density of TILs status.


Input: We further identified that B7-H4 is a cytoplasmic-nuclear shuttling protein containing a functional nuclear localization sequence (NLS) motif.


Input: A point mutation of B7-H4 NLS motif blocked the leptomycin B-induced nuclear accumulation of B7-H4.


Input: HEK293 cells stably expressing B7-H4 NLS mutant exhibited more potent inhibition in T-cell proliferation and cytokine production through increasing its surface expression compared with wild-type B7-H4 transfected cells owing to their increased surface expression.


Input: Most importantly, overexpression of wild-type B7-H4 in HEK293 cells enhanced tumor cell proliferation in vitro and tumorigenicity in vivo, promoted G1/S phase transition.


Input: The regulation of cell cycle by wild-type B7-H4 was partialy due to upregulation of Cyclin D 1 and Cyclin E.


Input: A mutation of B7-H4 NLS motif abolished the B7-H4-mediated cell proliferation and cell cycle regulation.


Input: Furthermore, B7-H4 wild-type confers chemoresistance activity to RCC cell lines including Caki-1 and ACHN.


Input: Our study provides a new insight into the functional implication of B7-H4 in its subcellular localization. Oncogene advance online publication, 14 January 2013; doi: 10. 1038/onc. 2012. 600.


Input: Papillary thyroid carcinoma arising from a thyroglossal duct cyst: a single institution experience.


Input: Thyroid cancers arising from a thyroglossal duct cyst (TGDC) are rarely reported.


Input: No clear consensus exists regarding optimal management.


Input: In this light, TGDC carcinomas recently treated at Asan Medical Center, as well as previously reported cases in the literature, were reviewed.


Input: There were ten patients who were diagnosed with TGDC carcinoma at our institution.


Input: All patients underwent pre-operative fine-needle aspiration biopsy (FNAB).


Input: Nine patients were suspected of having papillary carcinoma following cytology.


Input: The Sistrunk operation (SO) was performed in four patients, SO with total thyroidectomy (SO/TT) was performed in three patients, and SO/TT with neck dissection was performed in three patients.


Input: Six patients who received total thyroidectomy underwent radioactive iodine (RAI) therapy and T4 suppression.

iodine


Input: With a median follow-up period of 28. 5 months, two patients showed recurrence and one of them died of the disease.


Input: We analyzed 163 cases from 1990 to 2012 with three or more cases TGDC carcinoma, including the present study.


Input: Among 48 patients who underwent FNAB, 75% had papillary thyroid carcinoma (PTC).


Input: SO, SO/TT, or SO/TT with neck dissection was performed in 27%, 41%, and 32% of patients, respectively.


Input: Among 119 patients who received total thyroidectomy, 36% had concomitant PTC in the thyroid.


Input: Among 52 patients who received neck dissection, 69% had cervical nodal involvement.


Input: The results of our review suggest that when TGDC carcinoma is suspected, ultrasonography and, if necessary, FNAB should be performed.


Input: If these tests reveal a suspected lesion in the thyroid or lymph node, SO/TT and lymph node dissection should be performed.


Input: The in vitro and in vivo genotoxicity of isotretinoin assessed by cytokinesis blocked micronucleus assay and comet assay.

isotretinoin


Input: Isotretinoin is a retinoic acid frequently used in monotherapy or combined with narrow-band ultraviolet B (NBUVB) irradiation to treat patients with acne and psoriasis vulgaris.

Isotretinoin

retinoic acid


Input: As both diseases need frequent and/or prolonged therapeutic interventions, the study of the genotoxicity of retinoids becomes important.

retinoids


Input: Our aim was to study the genotoxic effects of isotretinoin alone or combined with NBUVB.

isotretinoin


Input: In vitro studies were performed in the absence of S9 metabolic activation using blood from five healthy volunteers, incubated 72 h with isotretinoin (1. 2-20 mu M) (i. e., at concentrations usually achieved in blood with therapeutic doses as well as at higher concentrations).

isotretinoin


Input: In vivo studies were also performed using blood from two patients with acne and three patients with psoriasis vulgaris treated with isotretinoin in monotherapy (8 or 20mg/day) or combined with NBUVB (20mg isotretinoin/day + NBUVB).

isotretinoin

isotretinoin


Input: The genotoxic effect was evaluated by the cytokinesis-blocked micronucleus and the comet assays.


Input: Our studies showed that isotretinoin alone was not genotoxic when tested in human lymphocytes in vitro and in vivo.

isotretinoin


Input: There was no clear genotoxic effect in psoriatic patients treated with isotretinoin and NBUVB.

isotretinoin


Input: The in vitro studies showed that isotretinoin induced apoptosis and necrosis in human lymphocytes at higher doses.

isotretinoin


Input: Platinum folate nanoparticles toxicity: cancer vs. normal cells.

Platinum folate


Input: Almost for two decades metallic nanoparticles are successfully used for cancer detection, imaging and treatment.


Input: Due to their high electron density they can be easily observed by electron microscopy and used in laser and radiofrequency therapy as energy releasing agents.


Input: However, the limitation for this practice is an inability to generate tumor-specific heating in a minimally invasive manner to the healthy tissue.


Input: To overcome this restraint we proposed to use folic acid coated metallic nanoparticles and determine whether they preferentially penetrate cancer cells.

folic acid


Input: We developed technique for synthesizing platinum nanoparticles using folic acid as stabilizing agent which produced particles of relatively narrow size distribution, having d = 2. 3 +/- 0. 5 nm.

platinum

folic acid


Input: High resolution TEM and zeta potential analysis indicated that the particles produced by this method had a high degree of crystalline order with no amorphous outer shell and a high degree of colloidal stability.


Input: The keratinocytes and mammary breast cells (cancer and normal) were incubated with platinum folate nanoparticles, and the results showed that the IC50 was significantly higher for the normal cells than the cancer cells in both cases, indicating that these nanoparticles preferentially target the cancer cells.

platinum folate


Input: TEM images of thin sections taken from the two types of cells indicated that the number of vacuoles and morphology changes after incubation with nanoparticles was also larger for the cancer cells in both types of tissue studied.


Input: No preferential toxicity was observed when folic acid receptors were saturated with free folic acid prior to exposure to nanoparticles.

folic acid

folic acid


Input: These results confirm our hypothesis regarding the preferential penetration of folic acid coated nanoparticles to cancer cells due to receptor mediated endocytosis.

folic acid


Input: Identification of benzofuran-3-yl (phenyl) methanones as novel SIRT1 inhibitors: binding mode, inhibitory mechanism and biological action.

benzofuran-3-yl (phenyl) methanones


Input: SIRT1 is a NAD (+)-dependent deacetylase.

NAD (+)


Input: Here we described new SIRT1 inhibitors with the scaffold of benzofuran-3-yl (phenyl) methanone.

benzofuran-3-yl (phenyl) methanone


Input: The inhibitors were predicted to bind in C-pocket of SIRT1, forming hydrophobic interactions with Phe273, Phe312 and Ile347.


Input: Introducing hydroxyl to meta position of phenyl may form H-bond with Asn346.

hydroxyl

phenyl

H


Input: Indeed, (2, 5-dihydroxyphenyl) (5-hydroxy-1-benzofuran-3-yl) methanone (16), an analogue with hydroxyls at ortho and meta positions, showed greater inhibition.

(2, 5-dihydroxyphenyl) (5-hydroxy-1-benzofuran-3-yl) methanone

hydroxyls


Input: The binding mode was validated by structural modifications and kinetic studies.


Input: Since C-pocket is the site where the nicotinamide moiety of NAD (+) binds and the hydrolysis takes place, binding of 16 in C-pocket would block the transformation of NAD (+) to productive conformation and hence inhibit the deacetylase activity.

nicotinamide

NAD (+)

NAD (+)


Input: Consistently, 16 inhibited SIRT1 through up-regulating p53 acetylation on cellular level.


Input: Comparison of orientation and rotational motion of skeletal muscle cross-bridges containing phosphorylated and dephosphorylated myosin regulatory light chain.


Input: Calcium binding to thin filaments is a major element controlling active force generation in striated muscles.

Calcium


Input: Recent evidence suggests that processes other than Ca (2 +) binding, such as phosphorylation of myosin regulatory light chain (RLC) also controls contraction of vertebrate striated muscle (Cooke, R. (2011) Biophys. Rev. 3, 33-45).

Ca (2 +)


Input: Electron paramagnetic resonance (EPR) studies using nucleotide analog spin label probes showed that dephosphorylated myosin heads are highly ordered in the relaxed fibers and have very low ATPase activity.

nucleotide


Input: This ordered structure of myosin cross-bridges disappears with the phosphorylation of RLC (Stewart, M. (2010) Proc. Natl. Acad. Sci. U. S. A. 107, 430-435).


Input: The slower ATPase activity in the dephosporylated moiety has been defined as a new super-relaxed state (SRX).


Input: It can be observed in both skeletal and cardiac muscle fibers (Hooijman, P., Stewart, M. A., and Cooke, R. (2011) Biophys. J. 100, 1969-1976).


Input: Given the importance of the finding that suggests a novel pathway of regulation of skeletal muscle, we aim to examine the effects of phosphorylation on cross-bridge orientation and rotational motion.


Input: We find that: (i) relaxed cross-bridges, but not active ones, are statistically better ordered in muscle where the RLC is dephosporylated compared with phosphorylated RLC; (ii) relaxed phosphorylated and dephosphorylated cross-bridges rotate equally slowly; and (iii) active phosphorylated cross-bridges rotate considerably faster than dephosphorylated ones during isometric contraction but the duty cycle remained the same, suggesting that both phosphorylated and dephosphorylated muscles develop the same isometric tension at full Ca (2 +) saturation.

Ca (2 +)


Input: A simple theory was developed to account for this fact.


Input: Methylation of histone H3 on lysine 4 by the lysine methyltransferase SET1 protein is needed for normal clock gene expression.

lysine

lysine


Input: The circadian oscillator controls time-of-day gene expression by a network of interconnected feedback loops and is reset by light.


Input: The requisite for chromatin regulation in eukaryotic transcription necessitates temporal regulation of histone-modifying and chromatin-remodeling enzymes for proper clock function.


Input: CHD1 is known to bind H3K4me3 in mammalian cells, and Neurospora CHD1 is required for proper regulation of the frequency (frq) gene.


Input: Based on this, we examined a strain lacking SET1 to determine the role of H3K4 methylation in clock-and light-mediated frq regulation.


Input: Expression of frq was altered in strains lacking set1 under both circadian-and light-regulated gene expression.


Input: There is a delay in the phasing of H3K4me3 relative to the peak in frq expression.


Input: White Collar 2 (WC-2) association with the frq promoter persists longer in Delta set1, suggesting a more permissible chromatin state.


Input: Surprisingly, SET1 is required for DNA methylation in the frq promoter, indicating a dependence on H3K4me for DNA methylation.


Input: The data support a model where SET1 is needed for proper regulation by modulating chromatin at frq.


Input: Inhibitory effect of anthocyanidins on hepatic glutathione S-transferase, UDP-glucuronosyltransferase and carbonyl reductase activities in rat and human.

anthocyanidins

glutathione S

UDP

carbonyl


Input: Abstract 1.


Input: Anthocyanins and their aglycone anthocyanidins represent the most abundant flavonoids in human diet and popular constituents of various dietary supplements.

Anthocyanins

anthocyanidins

flavonoids


Input: The aim of this study was to evaluate inhibitory effect of four anthocyanidins (delphinidin, cyanidin, malvidin and pelargonidin) on three families of important drug-metabolizing enzymes: carbonyl reductases (CBRs), glutathione S-transferases (GSTs) and UDP-glucuronosyltransferases (UGT).

anthocyanidins

delphinidin

cyanidin

malvidin

pelargonidin

carbonyl

glutathione S

UDP


Input: Human or rat hepatic subcellular fractions were incubated with or without pure anthocyanidins (100 micro M) and the activities of CBR, GST and UGT were assayed using menadione, 1-chloro-2, 4-dinitrobenzene and p-nitrophenol as substrates, respectively.

anthocyanidins

menadione

1-chloro-2, 4-dinitrobenzene

p-nitrophenol


Input: For the most potent inhibitors, half maximal inhibitory concentrations (IC (50)) were determined and the inhibition kinetics study was performed.


Input: Anthocyanidins inhibited weakly the activity of GST and moderately the activities of CBR and UGT.

Anthocyanidins


Input: Cyanidin was the most potent inhibitor of human UGT with IC (50) = 69 micro M (at 200 micro M substrate concentration) and competitive type of action.

Cyanidin


Input: Delphinidin acted as significant non-competitive inhibitor of human CBR with IC (50) = 16 micro M (at substrate concentration 500 micro M).

Delphinidin


Input: The inhibitory potency of anthocyanidins differed in rat and human samples significantly.

anthocyanidins


Input: Anthocyanidins are able to inhibit CBR and UGT in vitro.

Anthocyanidins


Input: Possible interference of anthocyanidins (in high-dose dietary supplements) with simultaneously administered drugs, which are UGT or CBR substrates, should be checked.

anthocyanidins


Input: An adhesive bone marrow scaffold and bone morphogenetic-2 protein carrier for cartilage tissue engineering.


Input: A chondroitin sulfate-bone marrow (CS-BM) adhesive hydrogel was used to localize rhBMP-2 to enhance articular cartilage tissue formation.

sulfate


Input: Chondrocyte pellet culture revealed that 0. 1 and 1 mu g/mL of rhBMP-2 enhanced sulfated-GAG content.


Input: rhBMP-2 localization within the hydrogels was investigated, and it was found that BM, CS-NHS, and rhBMP-2 levels and time affected rhBMP-2 retention.


Input: Retention was modulated from 82 to 99% over a 3-week period for the material formulations investigated.


Input: To evaluate carrier efficacy, rhBMP-2 and bovine articular chondrocytes were encapsulated within CS-BM, and biochemical evaluation revealed significant increases in total collagen production with rhBMP-2.


Input: Histological analysis revealed more robust tissue formation and greater type-II collagen production with encapsulated rhBMP-2.


Input: Subsequently, a subcutaneous culture of hydrogels revealed increased total collagen, type-II to type-I collagen ratio, and sulfated GAG in samples carrying rhBMP-2.


Input: These findings indicate the development of a multifunctional system capable of localizing rhBMP-2 to enhance repair tissue quality.


Input: Novel antiviral activity of l-dideoxy bicyclic nucleoside analogues versus vaccinia and measles viruses in vitro.

l-dideoxy bicyclic nucleoside


Input: Dideoxy bicyclic pyrimidine nucleoside analogues (ddBCNAs) with d-chirality have previously been described by us to inhibit replication of human cytomegalovirus.

Dideoxy bicyclic pyrimidine nucleoside

ddBCNAs


Input: We herein report for the first time that activity against vaccinia virus (VACV) was achieved using novel l-analogues.


Input: A structure-activity relationship was established: Antiviral activity versus VACV was highest with an ether side chain with an optimum of n-C (9) H (18)-O-n-C (5) H (11).

ether

n-C (9) H (18)-O-n-C (5) H (11)


Input: This gave an IC (50) of 190 nM, a 60-fold enhancement over the FDA-approved antiviral cidofovir.

cidofovir


Input: Interestingly, l-ddBCNAs also inhibit wild type measles virus syncytia formation with a TCID (50) of 7. 5 mu M for the lead compound.

ddBCNAs


Input: We propose that l-ddBCNAs represent significant innovative antiviral candidates versus measles and poxviruses, and we suggest a mechanism of action versus one or more cellular targets that are essential for viral replication.

ddBCNAs


Input: Reversible recruitment and emission of DO3A-derived lanthanide complexes at ligating molecular films on gold.

lanthanide


Input: The recruitment of DO3A-derived lanthanide complexes by ligation to isophthalic acid and catechol-modified gold surfaces, and their resulting sensitization, is reported herein.

lanthanide

isophthalic acid

catechol


Input: Predictably pH-dependent surface recruitment is associated with the expected fingerprint europium and terbium emission characteristics.

europium

terbium


Input: The intensity of the lanthanide luminescence scales exponentially with spacer length, indicating a strong quenching interaction between the lanthanide and the gold surface.

lanthanide

lanthanide


Input: The switchable catechol oxidation state provides a means of electrochemically triggering the release of prior ligated complexes.

catechol


Input: Determination of very rapid molecular rotation by using the central electron paramagnetic resonance line.


Input: Picosecond rotational correlation times of perdeuterated tempone (PDT) are found in alkane and aromatic liquids by directly using the spectral width of the central electron paramagnetic resonance line.

perdeuterated tempone

PDT


Input: This is done by mathematically eliminating the nonsecular spectral density from the spectral parameter equations, thereby removing the need to assume a particular form for it.


Input: This is preferable to fitting a constant correction factor to the spectral density, because such a factor does not fit well in the low picosecond range.


Input: The electron-nuclear spin dipolar interaction between the probe and solvent is shown to be negligible for the very rapid rotation of PDT in these liquids at the temperatures of the study.

PDT


Input: The rotational correlation times obtained with the proposed method generally agree to within experimental uncertainty with those determined by using the traditional parameters.


Input: Using the middle line width offers greater precision and smoother trends.


Input: Previous work with the central line width is discussed, and past discrepancies are explained as possibly resulting from residual inhomogeneous broadening.


Input: The rotational correlation time almost forms a common curve across all of the solvents when plotted with respect to isothermal compressibility, which shows the high dependence of rotation on liquid free volume.


Input: Further evidence for the sleep-promoting effects of 5-HT2A receptor antagonists and demonstration of synergistic effects with the hypnotic, zolpidem in rats.

zolpidem


Input: 5-Hydroxytryptamine (5-HT) 2A antagonists are promising therapeutic agents for the treatment of sleep maintenance insomnias, but unlike hypnotics, they have limited effects on sleep initiation.


Input: This study evaluated the effects of several 5-HT2A antagonists (eplivanserin, volinanserin and AVE8488) alone and/or in combination with the short-acting hypnotic, zolpidem, on the rat sleep profile.

eplivanserin

volinanserin

zolpidem


Input: A repeated-measures design was used in which rats were treated with eplivanserin (3 and 10 mg/kg, i. p. or p. o.), volinanserin (0. 3-3 mg/kg, i. p.), AVE8488 (0. 1-3 mg/kg, i. p.) and zolpidem (3 and 10 mg/kg, p. o.).

eplivanserin

volinanserin

zolpidem


Input: In addition, animals received a combination of eplivanserin (3 mg/kg, p. o.) and zolpidem (3 mg/kg, p. o.).

eplivanserin

zolpidem


Input: Electroencephalogram was analyzed for 6 h after administration.


Input: Eplivanserin did not modify wakefulness and non-rapid eye movement sleep (NREMS), while zolpidem (10 mg/kg po) induced a marked increase in NREMS duration.

Eplivanserin

zolpidem


Input: Volinanserin (1 and 3 mg/kg) and AVE8488 (0. 3 mg/kg) similarly increased NREMS, while reducing wakefulness.

Volinanserin


Input: Moreover, the 5-HT2A antagonists and, to a lesser extent, zolpidem, increased duration of NREMS episodes, while decreasing their frequency.

zolpidem


Input: When eplivanserin was co-administered with zolpidem, a synergistic effect was observed as the combination produced an increase in NREMS time and bouts duration.

eplivanserin

zolpidem


Input: These findings confirm further that 5-HT2A antagonists promote the maintenance of sleep, and suggest that combining a 5-HT2A antagonist with a short-acting hypnotic may be a useful strategy for the treatment of insomnia.


Input: Assessment of permethylated transition-metal sandwich complexes as internal reference redox systems in ionic liquids.

permethylated transition-metal


Input: This work reports the voltammetric behaviour of decamethylcobaltocenium, DmCc (+), in different ionic liquids for the first time.

decamethylcobaltocenium

DmCc (+)


Input: Its redox potential was studied relative to that of decamethylferrocene, DmFc, and it is shown that the difference in the mid-point potential between these two permethylated transition-metal sandwich complexes is independent of the ionic liquid composition.

decamethylferrocene

DmFc

permethylated transition-metal


Input: A variable difference in mid-point potential, in contrast, was observed for ferrocene and cobaltocenium relative to that of DmFc in similar ionic liquids.

ferrocene

cobaltocenium

DmFc


Input: In addition, different limitations in the application of DmFc (0/+) and DmCc (+/0) couples as internal reference redox systems in ILs are discussed.

DmFc (0/+)

DmCc (+/0)


Input: From these, the observed spontaneous reaction between DmFc and oxygen leads to important implications toward the establishment of particular conditions for DmFc applications.

DmFc

DmFc


Input: Carnitine palmitoyltransferase 2 and carnitine/acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines.

Carnitine

carnitine

acylcarnitine

acylcarnitines


Input: Acylcarnitines are commonly used in the diagnosis of mitochondrial fatty acid beta-oxidation disorders (mFAODs).

Acylcarnitines

fatty acid


Input: It is generally assumed that this plasma acylcarnitine profile reflects the mitochondrial accumulation of acyl-CoAs.

acylcarnitine

acyl-CoAs


Input: The identity of the enzymes and the mitochondrial and plasmalemmal transporters involved in the synthesis and export of these metabolites have remained undefined.


Input: We used lentiviral shRNA to knock down the expression of medium-chain acyl-CoA dehydrogenase (MCAD) in control and carnitine palmitoyltransferase 2 (CPT2)-, carnitine/acylcarnitine translocase (CACT)-, and plasmalemmal carnitine transporter (OCTN2)-deficient human fibroblasts.

acyl-CoA

carnitine

carnitine

acylcarnitine

carnitine


Input: These cell lines, including mock-transduced controls, were loaded with decanoic acid and carnitine, followed by the measurement of the acylcarnitine profile in the extracellular medium.

decanoic acid

carnitine

acylcarnitine


Input: In control fibroblasts, MCAD knockdown markedly increased the production of octanoylcarnitine (3-fold, P < 0. 01).

octanoylcarnitine


Input: OCTN2-deficient cell lines also showed extracellular accumulation of octanoylcarnitine (2. 8-fold, P < 0. 01), suggesting that the cellular export of acylcarnitines does not depend on OCTN2.

octanoylcarnitine

acylcarnitines


Input: In contrast, in CPT2-and CACT-deficient cells, the accumulation of octanoylcarnitine in the medium did not significantly increase in the MCAD knockdown.

octanoylcarnitine


Input: Similar results were obtained using pharmacological inhibition of CPT2 in fibroblasts from MCAD-deficient individuals.


Input: This shows that CPT2 and CACT are crucial for mitochondrial acylcarnitine formation and export to the extracellular fluids in mFAOD.-Violante, S., IJlst, L., te Brinke, H., Tavares de Almeida, I., Wanders, R.

acylcarnitine


Input: J.


Input: A., Ventura, F.


Input: V., Houten, S.


Input: M.


Input: Carnitine palmitoyltransferase 2 and carnitine/acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines.

Carnitine

carnitine

acylcarnitine

acylcarnitines


Input: Emerging mechanistic targets in lung injury induced by combustion-generated particles.


Input: The mechanism for biological effect following exposure to combustion-generated particles is incompletely defined.


Input: The identification of pathways regulating the acute toxicological effects of these particles provides specific targets for therapeutic manipulation in an attempt to impact disease following exposures.


Input: Transient receptor potential (TRP) cation channels were identified as " particle sensors " in that their activation was coupled with the initiation of protective responses limiting airway deposition and inflammatory responses, which promote degradation and clearance of the particles.


Input: TRPA1, V1, V4, and M8 have a capacity to mediate adverse effects after exposure to combustion-generated particulate matter (PM); relative contributions of each depend upon particle composition, dose, and deposition.


Input: Exposure of human bronchial epithelial cells to an organic extract of diesel exhaust particle was followed by TRPV4 mediating Ca (+ +) influx, increased RAS expression, mitogen-activated protein kinase signaling, and matrix metalloproteinase-1 activation.

Ca (+ +)


Input: These novel pathways of biological effect can be targeted by compounds that specifically inhibit critical signaling reactions.


Input: In addition to TRPs and calcium biochemistry, humic-like substances (HLS) and cell/tissue iron equilibrium were identified as potential mechanistic targets in lung injury after particle exposure.

calcium

iron


Input: In respiratory epithelial cells, iron sequestration by HLS in wood smoke particle (WSP) was associated with oxidant generation, cell signaling, transcription factor activation, and release of inflammatory mediators.

iron


Input: Similar to WSP, cytotoxic insoluble nanosized spherical particles composed of HLS were isolated from cigarette smoke condensate.


Input: Therapies that promote bioelimination of HLS and prevent the disruption of iron homeostasis could function to reduce the harmful effects of combustion-generated PM exposure.

iron


Input: Copper tolerance and genetic diversity of Porcellionides sexfasciatus (ISOPODA) in a highly contaminated mine habitat.

Copper


Input: Organisms inhabiting metal-contaminated areas may develop metal tolerance, with either phenotypic adjustments or genetic changes (adaptation) or with both.


Input: In the present study, three populations of the terrestrial isopod Porcellionides sexfasciatus, collected at an abandoned mine area, were compared to assess the effects of metal contamination on tolerance to lethal and sublethal levels of copper, through comparison of survival, avoidance, and feeding.

copper


Input: The effects of metal contamination on genetic diversity were considered using random amplified polymorphic DNA (RAPD) markers.


Input: No evidence of increased metal tolerance of the population inhabiting the contaminated site was found.


Input: There was no correlation between metal exposure and within-population genetic variance, but the three populations were clearly separated from each other.


Input: In conclusion, the populations of P. sexfasciatus in the mine landscape live rather isolated from each other and show no differential tolerance to Cu or indications of genetic erosion.


Input: Their phenotypic plasticity provides a means to survive despite exposure to extremely high metal concentrations in the soil.


Input: New monoterpene lactones from Actaea cimicifuga.

monoterpene lactones


Input: Three new monoterpene lactones, cimicifugolides A-C (1-3), along with a known one (4), were identified from the dried rhizome of Actaea cimicifuga L. that was used as traditional Chinese medicine for thousands of years with the Chinese common name of shengma.

monoterpene lactones

cimicifugolides A-C


Input: The structures of the new isolates were established using spectroscopic methods, including NMR, mass, UV, and IR spectra.


Input: The inhibition activity of compounds 1, 2, and 4 against pancreatic lipase was evaluated.


Input: Structure-activity relationships of glucosamine-derived glycerolipids: the role of the anomeric linkage, the cationic charge and the glycero moiety on the antitumor activity.

glucosamine

glycerolipids


Input: The potent antitumor activity of 1-O-hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-beta-D-glucopyranosyl)-sn-glycerol (1) was previously shown to arise through an apoptosis-independent pathway.

1-O-hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-beta-D-glucopyranosyl)-sn-glycerol


Input: Here, a systematic structure-activity study in which the effects of the anomeric linkage, the cationic charge and the glycero moiety on the antitumor activity is described.


Input: Eight analogues of 1 were synthesized, and their antitumor activity against breast (JIMT1 and BT549), pancreas (MiaPaCa2) and prostate (DU145, PC3) cancer was determined.


Input: 1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-alpha-D-glucopyranosyl)-sn-glycerol (2) consistently displayed the most potent activity against all five cell lines with CC (50) values in the range of 6-10 mu M.

1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-alpha-D-glucopyranosyl)-sn-glycerol


Input: However, replacement of the O-glycosidic linkage by a thioglycosidic linkage or replacement of the amino group by an azide or guanidino group leads to a threefold or greater decrease in potency.

O

thioglycosidic

amino

azide

guanidino


Input: The glycero moiety also contributes to the overall activity of 1 and 2 but its effects are of lesser importance.

glycero


Input: Investigation into the mode of action of this class of compounds revealed that, in agreement with previous findings, the cytotoxic effects arise through induction of large acid vacuoles.


Input: A unique palladium catalyst for efficient and selective alkoxycarbonylation of olefins with formates.

palladium

olefins

formates


Input: Forget about CO!

CO


Input: Carbonylations are among the most important homogeneously catalyzed reactions in the chemical industry, but typically require carbon monoxide.

carbon monoxide


Input: Instead, straightforward and efficient alkoxycarbonylations of olefins can proceed with alkyl formates in the presence of a specific palladium catalyst.

olefins

alkyl formates

palladium


Input: Aromatic, terminal aliphatic, and internal olefins are carbonylated to give industrially important linear esters at low catalyst loadings.

olefins

esters


Input: Synthesis, characterization, and cure chemistry of renewable bis (cyanate) esters derived from 2-methoxy-4-methylphenol.

bis (cyanate) esters


Input: A series of renewable bis (cyanate) esters have been prepared from bisphenols synthesized by condensation of 2-methoxy-4-methylphenol (creosol) with formaldehyde, acetaldehyde, and propionaldehyde.

bis (cyanate) esters

bisphenols

creosol

formaldehyde

acetaldehyde

propionaldehyde


Input: The cyanate esters have been fully characterized by infrared spectroscopy, (1) H and (13) C NMR spectroscopy, and single crystal X-ray diffraction.

cyanate esters

(1) H

(13) C


Input: These compounds melt from 88 to 143 degrees C, while cured resins have glass transition temperatures from 219 to 248 degrees C, water uptake (96 h, 85 degrees C immersion) in the range of 2. 05-3. 21%, and wet glass transition temperatures from 174 to 193 degrees C.


Input: These properties suggest that creosol-derived cyanate esters may be useful for a wide variety of military and commercial applications.

creosol

cyanate esters


Input: The cure chemistry of the cyanate esters has been studied with FTIR spectroscopy and differential scanning calorimetry.

cyanate esters


Input: The results show that cyanate esters with more sterically demanding bridging groups cure more slowly, but also more completely than those with a bridging methylene group.

cyanate esters

methylene


Input: In addition to the structural differences, the purity of the cyanate esters has a significant effect on both the cure chemistry and final Tg of the materials.

cyanate esters


Input: In some cases, post-cure of the resins at 350 degrees C resulted in significant decomposition and off-gassing, but cure protocols that terminated at 250-300 degrees C generated void-free resin pucks without degradation.


Input: Thermogravimetric analysis revealed that cured resins were stable up to 400 degrees C and then rapidly degraded.


Input: TGA/FTIR and mass spectrometry results showed that the resins decomposed to phenols, isocyanic acid, and secondary decomposition products, including CO2.

phenols

isocyanic acid


Input: Char yields of cured resins under N2 ranged from 27 to 35%, while char yields in air ranged from 8 to 11%.


Input: These data suggest that resins of this type may potentially be recycled to parent phenols, creosol, and other alkylated creosols by pyrolysis in the presence of excess water vapor.

phenols

creosol

alkylated creosols


Input: The ability to synthesize these high temperature resins from a phenol (creosol) that can be derived from lignin, coupled with the potential to recycle the composites, provides a possible route to the production of sustainable, high-performance, thermosetting resins with reduced environmental impact.

phenol

creosol


Input: In situ TEM of two-phase lithiation of amorphous silicon nanospheres.

silicon


Input: To utilize high-capacity Si anodes in next-generation Li-ion batteries, the physical and chemical transformations during the Li-Si reaction must be better understood.

Si

Li

Li-Si


Input: Here, in situ transmission electron microscopy is used to observe the lithiation/delithiation of amorphous Si nanospheres; amorphous Si is an important anode material that has been less studied than crystalline Si.

Si

Si

Si


Input: Unexpectedly, the experiments reveal that the first lithiation occurs via a two-phase mechanism, which is contrary to previous understanding and has important consequences for mechanical stress evolution during lithiation.


Input: On the basis of kinetics measurements, this behavior is suggested to be due to the rate-limiting effect of Si-Si bond breaking.

Si-Si


Input: In addition, the results show that amorphous Si has more favorable kinetics and fracture behavior when reacting with Li than does crystalline Si, making it advantageous to use in battery electrodes.

Si

Li

Si


Input: Amorphous spheres up to 870 nm in diameter do not fracture upon lithiation; this is much larger than the 150 nm critical fracture diameter previously identified for crystalline Si spheres.

Si


Input: Bioactive carboxylic acids from Lysimachia clethroides.

carboxylic acids


Input: Six new carboxylic acids (1-6), together with 11 known ones (7-17), were isolated from the aerial parts of Lysimachia clethroides.

carboxylic acids


Input: Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence.


Input: Five new carboxylic acids (1 and 3-6) were evaluated for their in vitro inhibitory activity against aldose reductase.

carboxylic acids

aldose


Input: Chemistry, chemoecology, and bioactivity of the South China Sea opisthobranch molluscs and their dietary organisms.


Input: Opisthobranchs are slow-moving, brightly colored, and shell-less slug.


Input: Interestingly, these naked molluscs appear to be free of predation causing great interests to biologists, chemists, and pharmacologists as well.


Input: It is well documented that their ability to escape predation is realized by utilizing chemical substances as defensive allomones.


Input: Due to their extraordinary capacity to produce a variety of chemical defensive molecules and in particular, some of which exhibited promising pharmacological activities, opisthobranch molluscs became the hotspot of research subject in the recent years.


Input: The authors and co-workers have systematically investigated the possible diet relationship between the South China Sea opisthobranch molluscs and their related prey organisms, including sponges, corals, and algae in the last decade.


Input: A series of interesting results have been obtained concerning the chemistry and chemoecology of the studied marine organisms.


Input: The present review focuses on recent development dealing with chemistry, chemoecology, and bioactivity of the South China Sea opisthobranch molluscs and their dietary organisms.


Input: Some selected representative examples are described in detail.


Input: Two new stemona alkaloids from Stemona tuberosa Lour.


Input: Two new pyrrolo [1, 2-alpha] azepine-type stemona alkaloids, named as tuberostemonoxirine (1) and 9 alpha-epi-tuberospironine (2), were isolated from the roots of Stemona tuberosa.

pyrrolo [1, 2-alpha] azepine

tuberostemonoxirine

9 alpha-epi-tuberospironine


Input: The structures and relative configurations of new compounds were established on the basis of extensive spectroscopic evidences, especially 1D and 2D NMR and HR-MS experiments.


Input: Design and application of anthracene derivative with aggregation-induced emission charateristics for visualization and monitoring of erythropoietin unfolding.

anthracene


Input: Erythropoietin (EPO) is an attractive protein-unfolding/folding model because of its high degree of unfolding and folding reversibility and intermediate size.


Input: Due to its function for regulating red blood cell production by stimulating late erythroid precursor cells, EPO presents obvious values to biological research.


Input: A nonemissive anthracene derivative, that is 9, 10-bis [4-(3-sulfonatopropoxyl)-styryl] anthracene sodium salt (BSPSA), with aggregation-induced emission (AIE) charateristics shows a novel phenomenon of AIE when EPO is added.

anthracene

9, 10-bis [4-(3-sulfonatopropoxyl)-styryl] anthracene sodium salt

BSPSA


Input: The AIE biosensor for EPO shows the limit of detection is 1 x 10 (-9) M.


Input: Utilizing the AIE feature of BSPSA, the unfolding process of EPO using guanidine hydrochloride is monitored, which indicates three steps for the folding structures of EPO to transform to random coil.

BSPSA

guanidine hydrochloride


Input: Computational modeling suggests that the BSPSA luminogens prefer docking in the hydrophobic cavity in the EPO folding structures, and the assembly of BSPSA in this cavity makes the AIE available, making the monitoring of unfolding of EPO possible.

BSPSA

BSPSA


Input: Heterogeneous cationic liposomes modified with 3 beta-{N-[(N', N'-dimethylamino) ethyl] carbamoyl} cholesterol can induce partial conformational changes in messenger RNA and regulate translation in an Escherichia coli cell-free translation system.

3 beta-{N-[(N', N'-dimethylamino) ethyl] carbamoyl} cholesterol


Input: The effect of cationic liposomes (CLs) on messenger RNA (mRNA) conformation and translation was studied, focusing on membrane heterogeneity.


Input: CLs, composed of 1, 2-dioleoyl-sn-glycerol-3-phosphocholine/1, 2-dioleoyl-3-timethylammonium propane (DOPC/DOTAP) and DOPC/3 beta-{N-[(N', N'-dimethylamino) ethyl] carbamoyl} cholesterol (DOPC/DC-Ch), inhibited mRNA translation in an Escherichia coli cell-free translation system.

1, 2-dioleoyl-sn-glycerol-3-phosphocholine

1, 2-dioleoyl-3-timethylammonium propane

DOPC

DOTAP

DOPC

3 beta-{N-[(N', N'-dimethylamino) ethyl] carbamoyl} cholesterol

DOPC

DC-Ch


Input: Analysis of the membrane fluidity and polarity indicated a heterogeneous DOPC/DC-Ch (70/30) membrane, while other CLs exhibited homogeneous disordered membranes.

DOPC

DC-Ch


Input: mRNA adsorbed onto DOPC/DC-Ch liposomes showed translational activity, while DOPC/DOTAP liposomes inhibited mRNA translation in proportion to its adsorption onto membranes.

DOPC

DC-Ch

DOPC

DOTAP


Input: Dehydration of DOPC/DOTAP (70/30) and DOPC/DC-Ch (70/30) was observed in the presence of mRNA but not in the case of zwitterionic DOPC liposomes, indicating that mRNA binds in regions between the phosphate [-PO (2) (-)-] and carbonyl [-C = O-] moieties of lipids.

DOPC

DOTAP

DOPC

DC-Ch

DOPC

phosphate

PO (2) (-)

carbonyl

C = O


Input: UV resonance Raman spectroscopy suggests that adenine, cytosine, and guanine interact with DOPC/DOTAP (70/30) and DOPC/DC-Ch (70/30) but not with DOPC.

adenine

cytosine

guanine

DOPC

DOTAP

DOPC

DC-Ch

DOPC


Input: Circular dichroism indicates that DOPC/DOTAP (70/30) extensively denatured the mRNA.

DOPC

DOTAP


Input: In contrast, heterogeneous DOPC/DC-Ch (70/30) induced partial conformational changes but maintained the translational activity of mRNA.

DOPC

DC-Ch


Input: Two new diterpenoids from Excoecaria acerifolia.

diterpenoids


Input: A new tigliane diterpenoid, acerifolin A (1), and a new isopimarane diterpenoid, acerifolin B (2), together with two known compounds, were isolated from Excoecaria acerifolia.

tigliane diterpenoid

acerifolin A

isopimarane diterpenoid

acerifolin B


Input: Their structures were elucidated on the basis of their spectroscopic methods, including 1D and 2D NMR techniques.


Input: All of the compounds were evaluated for cytotoxicity against five human cancer cell lines with cisplantin as a positive control.

cisplantin


Input: HOW GOOD IS THE LEVOTHYROXINE REPLACEMENT IN PRIMARY HYPOTHYROIDISM PATIENTS IN BRAZIL?-DATA OF A MULTICENTRE STUDY.

LEVOTHYROXINE


Input: Background: Studies done in every continent has shown that only around 50% of the patients subjected to thyroid hormone replacement have TSH in the normal range.


Input: However, until to date, there are no consistent data about Brazil.


Input: Objectives: To evaluate levothyroxine (LT4) replacement treatment in patients with primary hypothyroidism followed in referral centers in Brazil.

levothyroxine


Input: Methods: Patients with primary hypothyroidism followed in referral centers (University Hospitals from Universidade Federal do Rio de Janeiro-UFRJ, Unicamp, Universidade Federal do Paran a-UFPR and Universidade Federal do Cear a-UFC) answered a questionnairethat inquired about clinical and biochemical conditions, social-economic status, life quality and clinicians' orientations as well as their understanding about the information given.


Input: Serum TSH was checked close to the interview.


Input: Results: 2292 consecutive patients met the inclusion criteria.


Input: Mean age 51. 2 years and TSH values between 0. 4 and 4. 0 mUI/l were considered to be within the reference range.


Input: Among all patients taking thyroid medication, 42. 7%% had an abnormal serum TSH (28. 3% were undertreated and 14. 4% were over treated).


Input: Approximately all patients (99%) took LT4 in the morning but less than 30 minutes before breakfast (85. 4%).


Input: Regarding the clinicians' orientations: 97. 5% of the patients were instructed to take the medication daily, and 92. 6% to take 30 minutes before breakfast (92. 6%).


Input: However, only 52. 1% were told that not to take LT4 along with other medication.


Input: Conclusions: Our study found that there was a significant number of patients taking thyroid hormones were not in the therapeutic range.


Input: Clinicians should, therefore, consider monitoring patients on thyroid replacement more frequently and being more precise on giving recommendations about the correct use of LT4.


Input: Improved Postprandial Ghrelin Response by Nateglinide or Acarbose Therapy Contributes to Glucose Stability in Type 2 Diabetic Patients.

Nateglinide

Acarbose

Glucose


Input: Background: Recent studies highlight an important role of ghrelin in glucose homeostasis, while the association between ghrelin regulation and glucose fluctuation is unclear.

glucose

glucose


Input: Aim: We compared the effects of two postprandial hypoglycemic agents on ghrelin response and determined the contribution of ghrelin response to glucose stability in type 2 diabetic (T2DM) patients.

glucose


Input: Subjects and Methods: Forty newly-diagnosed T2DM patients were randomly allocated to receive Nateglinide or Acarbose for 4 weeks, with twenty BMI-matched normoglycemic subjects as controls.

Nateglinide

Acarbose


Input: Mean glucose values and daily average glucose excursion were assessed using continuous glucose monitoring system.

glucose

glucose

glucose


Input: Serum ghrelin levels were determined by ELISA.


Input: Results: T2DM patients had similar fasting ghrelin levels (P = 0. 546), while their postprandial ghrelin suppressions at 30 min and 120 min were reduced as compared to BMI-matched normoglycemic controls (P < 0. 01).


Input: Both Nateglinide and Acarbose increased postprandial ghrelin suppression at 120 min and reduced ghrelin area under the curve (AUCGHRL) (P < 0. 05), while only Nateglinide increased postprandial ghrelin suppression at 30 min (P < 0. 01), which was positively correlated with the increased early-phase insulin secretion by 4 weeks of Nateglinide therapy (r = 0. 48, P = 0. 05).

Nateglinide

Acarbose

Nateglinide

Nateglinide


Input: The decrease in AUCGHRL was positively correlated with the decrease in daily average glucose excursion and mean glucose values either by 4 weeks of Nateglinide or Acarbose therapy (P < 0. 05).

glucose

glucose

Nateglinide

Acarbose


Input: Conclusions: Both Natelinide and Acarbose increase postprandial ghrelin suppression.

Natelinide

Acarbose


Input: Improved ghrelin regulation is most likely to play a role in glucose stability in T2DM patients with Natelinide or Acarbose therapy.

glucose

Natelinide

Acarbose


Input: Stable Isolation of Phycocyanin from Spirulina platensis Associated with High-Pressure Extraction Process.


Input: A method for stably purifying a functional dye, phycocyanin from Spirulina platensis was developed by a hexane extraction process combined with high pressure.

hexane


Input: This was necessary because this dye is known to be very unstable during normal extraction processes.


Input: The purification yield of this method was estimated as 10. 2%, whose value is 3%-5% higher than is the case from another conventional separation method using phosphate buffer.


Input: The isolated phycocyanin from this process also showed the highest purity of 0. 909 based on absorbance of 2. 104 at 280 nm and 1. 912 at 620 nm.


Input: Two subunits of phycocyanin namely alpha-phycocyanin (18. 4 kDa) and beta-phycocyanin (21. 3 kDa) were found to remain from the original mixtures after being extracted, based on SDS-PAGE analysis, clearly demonstrating that this process can stably extract phycocyanin and is not affected by extraction solvent, temperature, etc.


Input: The stability of the extracted phycocyanin was also confirmed by comparing its DPPH (alpha, alpha-diphenyl-beta-picrylhydrazyl) scavenging activity, showing 83% removal of oxygen free radicals.

DPPH

alpha, alpha-diphenyl-beta-picrylhydrazyl

oxygen


Input: This activity was about 15% higher than that of commercially available standard phycocyanin, which implies that the combined extraction method can yield relatively intact chromoprotein through absence of degradation.


Input: The results were achieved because the low temperature and high pressure extraction effectively disrupted the cell membrane of Spirulina platensis and degraded less the polypeptide subunits of phycocyanin (which is a temperature/pH-sensitive chromoprotein) as well as increasing the extraction yield.


Input: Synthesis of bisindolylmethanes and their cytotoxicity properties.

bisindolylmethanes


Input: Polymer supported dichlorophosphate (PEG-OPOCl (2)) is an efficient green catalyst for the electrophilic substitution reaction of indole with aromatic aldehydes, in neat condition, to afford an excellent yield of bis (indolyl) methanes with short reaction time, at room temperature.

dichlorophosphate

PEG-OPOCl (2)

indole

aromatic aldehydes

bis (indolyl) methanes


Input: The synthesized compounds and their anti-cancer activity are evaluated.


Input: Can you enhance executive control without glucose?

glucose


Input: The effects of fructose on problem solving.

fructose


Input: The consumption of glucose can enhance executive control by increasing blood glucose and providing energy for brain processes.

glucose

glucose


Input: However, a glucose mouth rinse also positively affects executive control in the absence of an effect on blood glucose.

glucose

glucose


Input: This observation suggests that glucose can enhance executive control via another mechanism, perhaps by increasing cortical activation in motivational reward pathways.

glucose


Input: This hypothesis was examined in the current study by having participants consume fructose, glucose or a placebo 10 minutes before solving word anagrams.

fructose

glucose


Input: Fructose was used because it does not affect blood glucose levels, inhibits cortical responding, and cannot entrain a taste preference post-ingestion.

Fructose

glucose


Input: The latter evidences that fructose differs from glucose in its ability to elicit activation in motivational reward pathways.

fructose

glucose


Input: It was observed that consuming fructose and glucose resulted in the resolution of more anagrams than the placebo.

fructose

glucose


Input: These results suggest that at least some of the effects of glucose and fructose on problem solving operate through a common peripheral mechanism that is independent of motivational reward pathways.

glucose

fructose


Input: Binding site exploration of CCR5 using in silico methodologies: a 3D-QSAR approach.


Input: Chemokine receptor 5 (CCR5) is an important receptor used by human immunodeficiency virus type 1 (HIV-1) to gain viral entry into host cell.


Input: In this study, we used a combined approach of comparative modeling, molecular docking, and three dimensional quantitative structure activity relationship (3D-QSAR) analyses to elucidate detailed interaction of CCR5 with their inhibitors.


Input: Docking study of the most potent inhibitor from a series of compounds was done to derive the bioactive conformation.


Input: Parameters such as random selection, rational selection, different charges and grid spacing were utilized in the model development to check their performance on the model predictivity.


Input: Final comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were chosen based on the rational selection method, Gasteiger-H u ckel charges and a grid spacing of 0. 5 A.


Input: Rational model for CoMFA (q (2) = 0. 722, r (2) = 0. 884, Q (2) = 0. 669) and CoMSIA (q (2) = 0. 712, r (2) = 0. 825, Q (2) = 0. 522) was obtained with good statistics.


Input: Mapping of contour maps onto CCR5 interface led us to better understand of the ligand-protein interaction.


Input: Docking analysis revealed that the Glu283 is crucial for interaction.


Input: Two new amino acid residues, Tyr89 and Thr167 were identified as important in ligand-protein interaction.

amino acid


Input: No site directed mutagenesis studies on these residues have been reported.


Input: Identification and quantification of the sedative and anticonvulsant flavone glycoside from Chrysanthemum boreale.

flavone glycoside


Input: The flowers or leaves of Chrysanthemum boreale (Compositae) have been traditionally used as herb tea to reduce anxiety, insomnia, and stress.


Input: Sedative and anticonvulsant activities were evaluated in mice using pentobarbital-induced sleeping assay and pentylenetetrazole (PTZ)-induced convulsion assay.

pentobarbital

pentylenetetrazole

PTZ


Input: The flower extract exhibited more potent activities than the extracts of the leaves and stems, and chromatographic isolation yielded the five compounds acacetin, linarin, acacetin 7-O-beta-D-glucopyranosyl-(1 --> 2) [alpha-L-rhamnopyranosyl-(1 --> 6)]-beta-D-glucopyranoside, chlorogenic acid, and 3, 5-di-O-caffeoylquinic acid.

acacetin

linarin

acacetin 7-O-beta-D-glucopyranosyl-(1 --> 2) [alpha-L-rhamnopyranosyl-(1 --> 6)]-beta-D-glucopyranoside

chlorogenic acid

3, 5-di-O-caffeoylquinic acid


Input: These compounds were simultaneously analyzed by HPLC, and the method was validated.


Input: The contents of linarin, which were shown to be most abundant in C. boreale, were observed in the order of leaf (11. 93 mg/g) > flower (8. 50 mg/g) > stem (5. 60 mg/g).

linarin


Input: Linarin and its aglycone, acacetin, exhibited sedative and anticonvulsant activities in the present in vivo assays.

Linarin

acacetin


Input: It can be considered that linarin is one of the active compounds effective against anxiety, insomnia, and stress, with acacetin as its active moiety.

linarin

acacetin


Input: Stability of citrate-capped silver nanoparticles in exposure media and their effects on the development of embryonic zebrafish (Danio rerio).

citrate

silver


Input: The stability of citrate-capped silver nanoparticles (AgNPs) and the embryonic developmental toxicity were evaluated in the fish test water.

citrate

silver


Input: Serious aggregation of AgNPs was observed in undiluted fish water (DM-100) in which high concentration of ionic salts exist.


Input: However, AgNPs were found to be stable for 7 days in DM-10, prepared by diluting the original fish water (DM-100) with deionized water to 10%.


Input: The normal physiology of zebrafish embryos were evaluated in DM-10 to see if DM-10 can be used as a control vehicle for the embryonic fish toxicity test.


Input: As results, DM-10 without AgNPs did not induce any significant adverse effects on embryonic development of zebrafish determined by mortality, hatching, malformations and heart rate.


Input: When embryonic toxicity of AgNPs was tested in both DM-10 and in DM-100, AgNPs showed higher toxicity in DM-10 than in DM-100.


Input: This means that the big-sized aggregates of AgNPs were low toxic compared to the nano-sized AgNPs.


Input: AgNPs induced delayed hatching, decreased heart rate, pericardial edema, and embryo death.


Input: Accumulation of AgNPs in the embryo bodies was also observed.


Input: Based on this study, citrate-capped AgNPs are not aggregated in DM-10 and it can be used as a control vehicle in the toxicity test of fish embryonic development.

citrate


Input: Diclofenac: New data on chronic toxicity and bioconcentration in fish.

Diclofenac


Input: Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug that is regularly detected in surface waters.

Diclofenac

DCF


Input: To support a robust aquatic risk assessment, two early life stage (ELS) tests, compliant with the Organisation for Economic Co-operation and Development (OECD) test guideline 210, were conducted in rainbow trout and in zebrafish.


Input: Population relevant endpoints, such as hatching, growth, and survival, and in the trout study, histopathological effects in potential target organs, were examined.


Input: The bioconcentration of DCF in rainbow trout was measured in a separate study according to OECD test guideline 305.

DCF


Input: The bioconcentration factor (BCF) in rainbow trout remained below 10, demonstrating no relevant bioconcentration of DCF in fish.

DCF


Input: In the rainbow trout ELS test, the no observed effect concentration (NOEC) including histopathology was 320 micro g/L.


Input: The effect of DCF on zebrafish growth was less clear, and the NOEC can be interpreted as 10 micro g/L.

DCF


Input: However, for a number of reasons, the authors consider the moderately reduced growth of zebrafish exposed to concentrations of up to 320 micro g/L not a repeatable, treatment-related effect of DCF.

DCF


Input: This leads us to a conclusion that DCF has, with high probability, no adverse effect on both fish species up to 320 micro g/L.

DCF


Input: This NOEC indicates a sufficient safety margin for fish populations, because concentrations of DCF in European rivers are in the range of ng/L to low micro g/L.

DCF


Input: Caged CO (2) for the direct observation of CO (2)-consuming reactions.

CO (2)

CO (2)


Input: CO (2)-consuming reactions, in particular carboxylations, play important roles in technical processes and in nature.

CO (2)


Input: Their kinetic behavior and the reaction mechanisms of carboxylating enzymes are difficult to study because CO (2) is inconvenient to handle as a gas, exists in equilibrium with bicarbonate in aqueous solution, and typically yields products that show no significant spectroscopic differences from the reactants in the UV/Vis range.

CO (2)

bicarbonate


Input: Here we demonstrate the utility of 3-nitrophenylacetic acid and related compounds (caged CO (2)) in conjunction with infrared spectroscopy as widely applicable tools for the investigation of such reactions, permitting convenient measurement of the kinetics of CO (2) consumption.

3-nitrophenylacetic acid

CO (2)

CO (2)


Input: The use of isotopically labeled caged CO (2) provides a tool for the assignment of infrared absorption bands, thus aiding insight into reaction intermediates and mechanisms.

CO (2)


Input: Isolation and identification of cell-specific microRNAs targeting a messenger RNA using a biotinylated anti-sense oligonucleotide capture affinity technique.


Input: MicroRNAs (miRNAs) are small non-coding RNAs that regulate expression by translational repression or messenger RNA (mRNA) degradation.


Input: Although numerous bioinformatic prediction models exist to identify miRNA-mRNA interactions, experimental validation of bona fide interactions can be difficult and laborious.


Input: Few methods can comprehensively identify miRNAs that target a single mRNA.


Input: We have developed an experimental approach to search for miRNAs targeting any mRNA using a capture affinity assay involving a biotinylated DNA anti-sense oligonucleotide.


Input: This method identifies miRNAs targeting the full length of the mRNA.


Input: The method was tested using three separate mRNA targets: alpha-1 antitrypsin (AAT) mRNA, interleukin-8 mRNA and secretory leucoprotease inhibitor mRNA.


Input: AAT mRNA-specific and total miRNAs from three different cell lines (monocytic THP-1, bronchial epithelial 16HBE14o-and liver HepG2 cells) were profiled, and validation studies revealed that AAT mRNA-specific miRNAs functionally target the AAT mRNA in a cell-specific manner, providing the first evidence of innate miRNAs selectively targeting and modulating AAT mRNA expression.


Input: Interleukin-8 and secretory leucoprotease inhibitor mRNAs and their cognate miRNAs were also successfully captured using this approach.


Input: This is a simple and an efficient method to potentially identify miRNAs targeting sequences within the full length of a given mRNA transcript.


Input: Coumarins from roots of Clausena excavata.

Coumarins


Input: Two new coumarins, clauexcavatins A (1) and B (2), along with seven known ones (3-9), were isolated from the roots of Clausena excavata Burm.

coumarins

clauexcavatins A (1) and B (2)


Input: f.


Input: (Rutaceae).


Input: Their structures were elucidated on the basis of spectral data.


Input: Physicochemical characterization of phosphopeptide/titanium dioxide interactions employing the quartz crystal microbalance technique.

titanium dioxide

quartz


Input: The rapidly growing field of phosphoproteomics has led to a strong demand for procedures enabling fast and reliable isolation and enrichment of phosphorylated proteins and peptides.


Input: During the past decade, several novel phosphopeptide enrichment methods based on the affinity of phosphoryl groups for titanium dioxide (TiO (2)) have been developed and tested.

phosphoryl

titanium dioxide

TiO (2)


Input: The ultimate goal of obtaining comprehensive phosphoproteomes has, however, been found difficult to achieve and the obtained results often vary, dependent on the enrichment method and protocol used.


Input: In the present study, the physical chemistry of the phosphopeptide binding to TiO (2) is investigated by means of measurements using a quartz crystal microbalance with dissipation monitoring (QCM-D).

TiO (2)

quartz


Input: Special emphasis is put on the effect of the degree of phosphorylation of the phosphopeptide, the impact of the primary amino acid structure, and the role of electrostatic interactions.

amino acid


Input: The results show that, in general, adsorption of phosphopeptides follows the Langmuir model and that the affinity for the TiO (2) surface increases in a nonlinear fashion with increasing degree of phosphorylation.

TiO (2)


Input: An exception was detected, however, where positive cooperativity between the peptides existed and the Langmuir model no longer applied.


Input: The source behind the cooperativity could be traced back to the primary amino acid structure and, more specifically, the presence of positively charged amino acids in positions that enable electrostatic interaction with phosphoryl groups on neighboring peptides.

amino acid

amino acids

phosphoryl


Input: Regardless of the net peptide charge, the TiO (2)-phosphopeptide interaction was for all phosphopeptides investigated found to be mainly of electrostatic origin.

TiO (2)


Input: This study highlights and explains some of the most common problems with the TiO (2)-based enrichment methods used today.

TiO (2)


Input: Surfactant-mediated control of colloid pattern assembly and attachment strength in evaporating droplets.


Input: This study demonstrates that the pattern assembly and attachment strength of colloids in an evaporating sessile droplet resting on a smooth substrate can be controlled by adding nonionic solutes (surfactant) to the solution.


Input: As expected, increasing the surfactant concentration leads to a decrease in initial surface tension of the drop, sigma (0).


Input: For the range of initial surface tensions investigated (39-72 mN m (-1)), three distinct deposition patterns were produced: amorphous stains (sigma (0) = 63-72 mN m (-1)), coffee-ring stains (sigma (0) = 48-53 mN m (-1)), and concentric rings (sigma (0) = 39-45 mN m (-1)).


Input: A flow-displacement system was used to measure the attachment strength of the dried colloids.


Input: Characteristic drying regimes associated with the three unique pattern formations are attributed to abrupt transitions of contact line dynamics during evaporation.


Input: The first transition from slipping-to pinned-contact line was found to be a direct result of the competition between mechanical instability of the droplet and the friction generated by pinned colloids at the contact line.


Input: The second transition from pinned-to recurrent-stick-rip-slip-contact line was caused by repeated liquid film rupturing from evaporation-intensified surfactant concentration.


Input: Data from flow-displacement tests indicate that attachment strength of dried particles is strongest for amorphous stains (lowest surfactant concentration) and weakest for concentric rings (highest surfactant concentration).


Input: The mechanism behind these observations was ascribed to the formation and adsorption of micelles onto colloid and substrate surfaces as the droplet solution evaporates.


Input: The range of attachment forces observed between the colloids and the solid substrate were well captured by extended-DLVO interactions accounting for van der Waals attraction, electric double layer repulsion, and micelle-protrusion repulsion.


Input: Both empirical and theoretical results suggest that an increasingly dense layer of adsorbed micellar-protrusions on colloid and substrate surfaces acts as a physical barrier that hinders strong van der Waals attractive interactions at close proximity.


Input: Thereby, colloid stains dried at higher surfactant concentrations are more easily detached from the substrate when dislodging forces are applied than stains dried at lower surfactant concentrations.


Input: Anxiogenic-like effects of Uncaria tomentosa (Willd.) DC. aqueous extract in an elevated plus maze test in mice: a preliminary study.


Input: The purpose of this study was to examine the effect of orally administered Uncaria tomentosa aqueous extracts (UTE) (Willd. ex Roem. & Schult.) DC.


Input: (Rubiaceae) during 7, 15, 30 and 90 days of treatment on the expression of anxiety, as expressed in the elevated plus maze test in male Albino Swiss mice.


Input: UTE revealed an anxiogenic effect in relation to the control group at 15 and 30 days, but it was reversed after 90 days of administration, without affecting the locomotor activity or any deleterious effects on the overall performance of the animal, either for its ambulation, or clinical status, and body weight and organ weight/body weight from liver, lung and kidney were unaffected.


Input: These biphasic effects are usually indicative of heterogeneity in sites of action due to the presence of many alkaloids (speciophylline, uncarine F and uncarine E) and flavanols (catechin and epigallocatechin) identified and isolated from UTE.

speciophylline

uncarine F

uncarine E

flavanols

catechin

epigallocatechin


Input: Cooperative effects for CYP2E1 differ between styrene and its metabolites.

styrene


Input: Abstract 1.


Input: Cooperative interactions are frequently observed in the metabolism of drugs and pollutants by cytochrome P450s; nevertheless, the molecular determinants for cooperativity remain elusive.


Input: Previously, we demonstrated that steady-state styrene metabolism by CYP2E1 exhibits positive cooperativity.


Input: We hypothesized that styrene metabolites have lower affinity than styrene toward CYP2E1 and limited ability to induce cooperative effects during metabolism.

styrene

styrene


Input: To test the hypothesis, we determined the potency and mechanism of inhibition for styrene and its metabolites toward oxidation of 4-nitrophenol using CYP2E1 Supersomes (R) and human liver microsomes.

styrene


Input: Styrene inhibited the reaction through a mixed cooperative mechanism with high affinity for the catalytic site (67 micro M) and lower affinity for the cooperative site (1100 micro M), while increasing substrate turnover at high concentrations.

Styrene


Input: Styrene oxide and 4-vinylphenol possessed similar affinity for CYP2E1.

Styrene oxide


Input: Styrene oxide behaved cooperatively like styrene, but 4-vinylphenol decreased turnover at high concentrations.

Styrene oxide

styrene


Input: Styrene glycol was a very poor competitive inhibitor.

Styrene glycol


Input: Among all compounds, there was a positive correlation with binding and hydrophobicity.


Input: Taken together, these findings for CYP2E1 further validate contributions of cooperative mechanisms to metabolic processes, demonstrate the role of molecular structure on those mechanisms and underscore the potential for heterotropic cooperative effects between different compounds.


Input: Characterisation of the essential oil from different aerial parts of Lindera chunii Merr.


Input: (Lauraceae).


Input: The essential oils from three organs (i. e. flowers, leaves and stems) of wild Lindera chunii Merr. in Dinghu Mountain (China) were obtained by microwave-assisted hydrodistillation.


Input: The essential oils were analysed by gas chromatography with flame ionisation detection and gas chromatography with mass spectrometry.


Input: The yields of essential oil varied from 0. 06% to 0. 59% and showed a remarkable variation among the plant organs.


Input: A total of 43 compounds accounting for 95. 4-96. 3% of the total essential oil were identified, and the major compounds were germacrene B (0. 7-43. 2%), viridiflorene (trace to 14. 6%), globulol (6. 3-11. 6%), alpha-cadinol (1. 7-8. 6%) and tau-cadinol (0. 5-7. 3%).

germacrene B

viridiflorene

globulol

alpha-cadinol

tau-cadinol


Input: This study shows that the chemical compositions of the essential oils from the different organs of L. chunii are very variable.


Input: Interactions between pectic compounds and procyanidins are influenced by methylation degree and chain length.

procyanidins


Input: The interactions between procyanidins and pectic compounds are of importance in food chemistry.

procyanidins


Input: Procyanidins with low (9) and high (30) average degrees of polymerization (DP9 and DP30) were extracted from two cider apple varieties.

Procyanidins


Input: Commercial apple and citrus pectins, as well as three pectin subfractions (homogalacturonans, partially methylated homogalacturonans with degree of methylation 30 and 70) at 30 mM galacturonic acid equivalent, were titrated with the two procyanidin fractions (at 30 mM (-)-epicatechin equivalent) by isothermal titration calorimetry and UV-vis spectrophotometry.

galacturonic acid

procyanidin

(-)-epicatechin


Input: Slightly stronger affinities were recorded between commercial apple or citrus pectins and procyanidins of DP30 (Ka = 1460 and 1225 M (-1) respectively, expressed per monomer units) compared to procyanidins of DP9 (Ka = 1240 and 1085 M (-1), respectively), but stoichiometry and absorbance maxima differed between apple and citrus pectins.

procyanidins

procyanidins


Input: It was proposed that methylated homogalacturonans interacted with procyanidins DP30 mainly through hydrophobic interactions.

procyanidins


Input: The stronger association was obtained with the longer procyanidin molecules interacting with highly methylated pectins.

procyanidin


Input: Pharmacogenomics as a risk mitigation strategy for chemotherapeutic cardiotoxicity.


Input: Damage to the heart can result from both traditional chemotherapeutic agents, such as doxorubicin, and newer' targeted' therapies, such as trastuzumab.

doxorubicin


Input: This chemotherapeutic cardiotoxicity is potentially life-threatening and necessitates limiting or discontinuing an otherwise-effective cancer treatment.


Input: Clinical strategies focus on surveillance rather than prevention, although there are no specific therapies for this highly morbid adverse effect.


Input: Current models for prospectively predicting risk of chemotherapeutic cardiotoxicity are limited.


Input: Cardiotoxicity can occur idiosyncratically in patients without obvious demographic risk factors, suggesting a genetically determined susceptibility, and candidate-gene studies have identified a limited number of variants that increase risk.


Input: In this commentary we indicate a need for more powerful means to identify risk prospectively, and suggest that broad pharmacogenomic approaches may be fruitful.


Input: Bioactive abietane and ent-kaurane diterpenoids from Isodon tenuifolius.

abietane

ent-kaurane diterpenoids


Input: Three new abietane diterpenoids, isoabietenins A-C (1-3), and 13 new ent-kauranoids, tenuifolins A-M (4-16), along with four known compounds (17-20), were isolated from the aerial parts of Isodon tenuifolius.

abietane diterpenoids

isoabietenins A-C

ent-kauranoids

tenuifolins A-M


Input: The structures of the new metabolites were established on the basis of detailed spectroscopic analysis.


Input: The absolute configurations of 1, 15, and 16 were confirmed by single-crystal X-ray diffraction.


Input: Selected compounds were evaluated for their cytotoxicity against a small panel of human tumor cell lines, and some compounds showed inhibitory effects.


Input: Furthermore, several isolates exhibited inhibitory activity against nitric oxide production in LPS-activated RAW264. 7 macrophages.

nitric oxide


Input: Long-loop G-quadruplexes are misfolded population minorities with fast transition kinetics in human telomeric sequences.


Input: Single-stranded guanine (G)-rich sequences at the 3' end of human telomeres provide ample opportunities for physiologically relevant structures, such as G-quadruplexes, to form and interconvert.


Input: Population equilibrium in this long sequence is expected to be intricate and beyond the resolution of ensemble-average techniques, such as circular dichroism, NMR, or X-ray crystallography.


Input: By combining a force-jump method at the single-molecular level and a statistical population deconvolution at the sub-nanometer resolution, we reveal a complex population network with unprecedented transition dynamics in human telomeric sequences that contain four to eight TTAGGG repeats.


Input: Our kinetic data firmly establish that G-triplexes are intermediates to G-quadruplexes while long-loop G-quadruplexes are misfolded population minorities whose formation and disassembly are faster than G-triplexes or regular G-quadruplexes.


Input: The existence of misfolded DNA supports the emerging view that structural and kinetic complexities of DNA can rival those of RNA or proteins.


Input: While G-quadruplexes are the most prevalent species in all the sequences studied, the abundance of a misfolded G-quadruplex in a particular telomeric sequence decreases with an increase in the loop length or the number of long-loops in the structure.


Input: These population patterns support the prediction that in the full-length 3' overhang of human telomeres, G-quadruplexes with shortest TTA loops would be the most dominant species, which justifies the modeling role of regular G-quadruplexes in the investigation of telomeric structures.


Input: Alkaloids from Microcos paniculata with cytotoxic and nicotinic receptor antagonistic activities.


Input: Microcos paniculata is a large shrub or small tree that grows in several countries in South and Southeast Asia.


Input: In the present study, three new piperidine alkaloids, microgrewiapines A-C (1-3), as well as three known compounds, inclusive of microcosamine A (4), 7'-(3', 4'-dihydroxyphenyl)-N-[4-methoxyphenyl) ethyl] propenamide (5), and liriodenine (6), were isolated from cytotoxic fractions of the separate chloroform-soluble extracts of the stem bark, branches, and leaves of M. paniculata.

piperidine alkaloids

microgrewiapines A-C

microcosamine A

7'-(3', 4'-dihydroxyphenyl)-N-[4-methoxyphenyl) ethyl] propenamide

liriodenine

chloroform


Input: Compounds 1-6 and 1a (microgrewiapine A 3-acetate) showed a range of cytotoxicity values against the HT-29 human colon cancer cell line.

microgrewiapine A 3-acetate


Input: When evaluated for their effects on human alpha 3 beta 4 or alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs), several of these compounds were shown to be active as nAChR antagonists.

acetylcholine


Input: As a result of this study, microgrewiapine A (1) was found to be a selective cytotoxic agent for colon cancer cells over normal colon cells and to exhibit nicotinic receptor antagonistic activity for both the h alpha 3 beta 4 and h alpha 4 beta 2 receptor subtypes.

microgrewiapine A


Input: Thioredoxin-mimetic peptides (TXM) reverse auranofin induced apoptosis and restore insulin secretion in insulinoma cells.

auranofin


Input: The thioredoxin reductase/thioredoxin system (TrxR/Trx1) plays a major role in protecting cells from oxidative stress.


Input: Disruption of the TrxR-Trx1 system keeps Trx1 in the oxidized state leading to cell death through activation of the ASK1-Trx1 apoptotic pathway.


Input: The potential mechanism and ability of tri-and tetra-oligopeptides derived from the canonical-CxxC-motif of the Trx1-active site to mimic and enhance Trx1 cellular activity was examined.


Input: The Trx mimetics peptides (TXM) protected insulinoma INS 832/13 cells from oxidative stress induced by selectively inhibiting TrxR with auranofin (AuF).

auranofin

AuF


Input: TXM reversed the AuF-effects preventing apoptosis, and increasing cell-viability.

AuF


Input: The TXM peptides were effective in inhibiting AuF-induced MAPK, JNK and p38 (MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation.

AuF


Input: The ability to form a disulfide-bridge-like conformation was estimated from molecular dynamics simulations.

disulfide


Input: The TXM peptides restored insulin secretion and displayed Trx1 denitrosylase activity.


Input: Their potency was 10-100-fold higher than redox reagents like NAC, AD4, or ascorbic acid.

NAC

ascorbic acid


Input: Unable to reverse ERK1/2 phosphorylation, TXM-CB3 (NAc-Cys-Pro-Cys amide) appeared to function in part, through inhibiting ASK1-Trx dissociation.

NAc-Cys-Pro-Cys amide


Input: These highly effective anti-apoptotic effects of Trx1 mimetic peptides exhibited in INS 832/13 cells could become valuable in treating adverse oxidative-stress related disorders such as diabetes.


Input: Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells.

vitamin D


Input: Fat infiltration within muscle is one of a number of features of vitamin D deficiency, which leads to a decline in muscle functionality.

vitamin D


Input: The origin of this fat is unclear, but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes.


Input: The current study examined the effect of the active form of vitamin D 3, 1, 25-dihydroxyvitamin D 3 (1, 25 (OH) 2 D 3), on the capacity of the C2C12 muscle cell line to differentiate towards the myogenic and adipogenic lineages.

vitamin D 3

1, 25-dihydroxyvitamin D 3

1, 25 (OH) 2 D 3


Input: Cells were cultured in myogenic or adipogenic differentiation media containing increasing concentrations (0, 10-(1) (3), 10-(1) (1), 10-9, 10-7 or 10-5 M) of 1, 25 (OH) 2 D 3 for up to 6 days and markers of muscle and fat development measured.

1, 25 (OH) 2 D 3


Input: Mature myofibres were formed in both adipogenic and myogenic media, but fat droplets were only observed in adipogenic media.


Input: Relative to controls, low physiological concentrations (10-(1) (3) and 10-(1) (1) M) of 1, 25 (OH) 2 D3 increased fat droplet accumulation, whereas high physiological (10-9 M) and supraphysiological concentrations (>= 10-7 M) inhibited fat accumulation.

1, 25 (OH) 2 D3


Input: This increased accumulation of fat with low physiological concentrations (10-(1) (3) and 10-(1) (1) M) was associated with a sequential up-regulation of PPAR gamma 2 (PPARG) and FABP4 mRNA, indicating formation of adipocytes, whereas higher concentrations (>= 10-9 M) reduced all these effects, and the highest concentration (10-5 M) appeared to have toxic effects.


Input: This is the first study to demonstrate dose-dependent effects of 1, 25 (OH) 2 D 3 on the transdifferentiation of muscle cells into adipose cells.

1, 25 (OH) 2 D 3


Input: Low physiological concentrations (possibly mimicking a deficient state) induced adipogenesis, whereas higher (physiological and supraphysiological) concentrations attenuated this effect.


Input: Omega-3 Fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance.

Omega-3 Fatty acids


Input: Fish oils (FOs) have anti-inflammatory effects and lower serum triglycerides.


Input: This study examined adipose and muscle inflammatory markers after treatment of humans with FOs and measured the effects of omega-3 fatty acids on adipocytes and macrophages in vitro.

omega-3 fatty acids


Input: Insulin-resistant, nondiabetic subjects were treated with Omega-3-Acid Ethyl Esters (4 g/day) or placebo for 12 weeks.

Omega-3-Acid Ethyl Esters


Input: Plasma macrophage chemoattractant protein 1 (MCP-1) levels were reduced by FO, but the levels of other cytokines were unchanged.


Input: The adipose (but not muscle) of FO-treated subjects demonstrated a decrease in macrophages, a decrease in MCP-1, and an increase in capillaries, and subjects with the most macrophages demonstrated the greatest response to treatment.


Input: Adipose and muscle omega-3 fatty acid content increased after treatment; however, there was no change in insulin sensitivity or adiponectin.

omega-3 fatty acid


Input: In vitro, M1-polarized macrophages expressed high levels of MCP-1.


Input: The addition of omega-3 fatty acids reduced MCP-1 expression with no effect on TNF-alpha.

omega-3 fatty acids


Input: In addition, omega-3 fatty acids suppressed the upregulation of adipocyte MCP-1 that occurred when adipocytes were cocultured with macrophages.

omega-3 fatty acids


Input: Thus, FO reduced adipose macrophages, increased capillaries, and reduced MCP-1 expression in insulin-resistant humans and in macrophages and adipocytes in vitro; however, there was no measureable effect on insulin sensitivity.


Input: Allele-Specific Transcriptional Activity at Type 2 Diabetes-Associated Single Nucleotide Polymorphisms in Regions of Pancreatic Islet Open Chromatin at the JAZF1 Locus.


Input: Translation of noncoding common variant association signals into meaningful molecular and biological mechanisms explaining disease susceptibility remains challenging.


Input: For the type 2 diabetes association signal in JAZF1 intron 1, we hypothesized that the underlying risk variants have cis-regulatory effects in islets or other type 2 diabetes-relevant cell types.


Input: We used maps of experimentally predicted open chromatin regions to prioritize variants for functional follow-up studies of transcriptional activity.


Input: Twelve regions containing type 2 diabetes-associated variants were tested for enhancer activity in 832/13 and MIN6 insulinoma cells.


Input: Three regions exhibited enhancer activity and only rs1635852 displayed allelic differences in enhancer activity; the type 2 diabetes risk allele T showed lower transcriptional activity than the nonrisk allele C.


Input: This risk allele showed increased binding to protein complexes, suggesting that it functions as part of a transcriptional repressor complex.


Input: We applied DNA affinity capture to identify factors in the complex and determined that the risk allele preferentially binds the pancreatic master regulator PDX1.


Input: These data suggest that the rs1635852 region in JAZF1 intron 1 is part of a cis-regulatory complex and that maps of open chromatin are useful to guide identification of variants with allelic differences in regulatory activity at type 2 diabetes loci.


Input: Benzophenone-1 stimulated the growth of BG-1 ovarian cancer cells by cell cycle regulation via an estrogen receptor alpha-mediated signaling pathway in cellular and xenograft mouse models.

estrogen