Effects of lycopene and apigenin on human umbilical vein endothelial cells in vitro under angiogenic stimulation.

Angiogenesis is the formation process of new blood vessels from preexisting vessels. Solid tumors need angiogenesis for growth and metastasis. The suppression of tumor growth by inhibition of neoangiogenic processes represents a potential approach to cancer treatment.

Inhibition of angiogenesis by S-adenosylmethionine.

Metastasis is a leading cause of mortality and morbidity in cancer. One of the steps in metastasis process is the formation of new blood vessels. Aberrant DNA methylation patterns are common in cancer cells.

Pancreatic cancers require autophagy for tumor growth.

Macroautophagy (autophagy) is a regulated catabolic pathway to degrade cellular organelles and macromolecules. The role of autophagy in cancer is complex and may differ depending on tumor type or context. Here we show that pancreatic cancers have a distinct dependence on autophagy.

The design and cytotoxic evaluation of some 1-aryl-3-isopropylamino-1-propanone hydrochlorides towards human Huh-7 hepatoma cells.

A series of 1-aryl-3-isopropylamino-1-propanone hydrochlorides 1 and a related heterocyclic analog 2 as candidate antineoplastic agents were prepared and the rationale for designing these compounds is presented. A specific objective in this study is the discovery of novel compounds possessing growth-inhibiting properties of hepatoma cells. The compounds in series 1 and 2 were prepared and their structures established unequivocally.

Telomere dysfunction induces metabolic and mitochondrial compromise.

Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1α and PGC-1β, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes.

New one-pot synthesis of spiro[furo[2,3-d]pyrimidine-6,5'-pyrimidine]pentaones and their sulfur analogues.

Reaction of barbituric acid (BA), 1,3-dimethyl barbituric acid (DMBA) and 2-thiobarbituric acid (TBA) with cyanogen bromide and various aldehydes in presence of triethylamine afforded a new class of heterocyclic stable 5-alkyl and/or 5-aryl-1H, 1'H-spiro[furo[2,3-d]pyrimidine-6,5'-pyrimidine]2,2',4,4',6'(3H,3'H,5H)-pentaones which are dimeric forms of barbiturate (uracil and thiouracil derivatives) at 0 °C to ambient temperatures. Structure elucidation is proved by X-ray crystallography, (1)H NMR, (13)C NMR, FT-IR, CHN and mass analyses techniques. Mechanisms of the formations are discussed.

KNK437, a benzylidene lactam compound, sensitises prostate cancer cells to the apoptotic effect of hyperthermia.

Hyperthermia is known to serve as a powerful tool in the treatment of prostate cancer which is commonly diagnosed in men. Quercetin and KNK437, Hsp70 inhibitors, play an important role in blocking thermotolerance in some cancer cells. In the present study we investigated the effects of KNK437 and quercetin on the acquisition of thermotolerance and heat-induced apoptosis.

Computational design and biophysical characterization of aggregation-resistant point mutations for γD crystallin illustrate a balance of conformational stability and intrinsic aggregation propensity.

γD crystallin is a natively monomeric eye-lens protein that is associated with hereditary juvenile cataract formation. It is an attractive model system as a multidomain Greek-key protein that aggregates through partially folded intermediates. Point mutations M69Q and S130P were used to test (1) whether the protein-design algorithm RosettaDesign would successfully predict mutants that are resistant to aggregation when combined with informatic sequence-based predictors of peptide aggregation propensity and (2) how the mutations affected relative unfolding free energies (ΔΔG(un)) and intrinsic aggregation propensity (IAP).

FabAct®: a decision-making tool for the anticipation of the preparation of anticancer drugs.

Rationale: Due to the increase of new cancer cases, our chemotherapy compounding unit must face with ever-growing production needs. To support this increasing workload, we decided to anticipate the preparation of several anti-cancer drugs.

Aims And Objectives: To help us in the decision making, we needed a modern tool able to combine several criteria for selecting appropriate medications for an anticipated preparation.

Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells.

The capacity to fine-tune cellular bioenergetics with the demands of stem-cell maintenance and regeneration is central to normal development and ageing, and to organismal survival during periods of acute stress. How energy metabolism and stem-cell homeostatic processes are coordinated is not well understood. Lkb1 acts as an evolutionarily conserved regulator of cellular energy metabolism in eukaryotic cells and functions as the major upstream kinase to phosphorylate AMP-activated protein kinase (AMPK) and 12 other AMPK-related kinases.

Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice.

An ageing world population has fuelled interest in regenerative remedies that may stem declining organ function and maintain fitness. Unanswered is whether elimination of intrinsic instigators driving age-associated degeneration can reverse, as opposed to simply arrest, various afflictions of the aged. Such instigators include progressively damaged genomes.

Enantioselective synthesis of cyclic, quaternary oxonitriles.

Quaternary oxonitriles are stereoselectively generated from the union of five-, six-, and seven-membered 2-chloroalkenecarbonitriles with chiral alcohols via a Claisen rearrangement. The strategy rests on a new conjugate addition-elimination of allylic alkoxides to 2-chlorocycloalkenecarbonitriles to afford substituted 2-alkoxyalkenenitriles. Subsequent thermolysis unmasks a cyclic oxonitrile while selectively forming a new quaternary center with enantiomeric ratios typically greater than 9:1.

Bonding of resin core materials to lithium disilicate ceramics: the effect of resin cement film thickness.

The aim of this study was to investigate the effect of different resin cement film thicknesses on the shear bond strength of resin core materials to lithium disilicate ceramics. Forty IPS Empress 2 ceramic disks were bonded to the core materials (Bis-core and Smile) with resin cement film thicknesses of 50 or 100 μm. Shear bond strength was measured using a universal testing machine.

Comparative effects of pH and ionic strength on protein-protein interactions, unfolding, and aggregation for IgG1 antibodies.

Changes in protein-protein interactions, protein unfolding, and nonnative aggregation were assessed for a series of human IgG1 antibodies as a function of pH and solution ionic strength (I). Unfolding transitions were characterized with differential scanning calorimetry. Protein-protein interactions were characterized with the apparent second virial coefficient (A(2)) from light scattering.

DNA methylation or histone modification status in metastasis and angiogenesis-related genes: a new hypothesis on usage of DNMT inhibitors and S-adenosylmethionine for genome stability.

Metastasis is a leading cause of mortality and morbidity in cancer. This process needs angiogenesis. The biology underlying cancer, metastasis, and angiogenesis has been investigated so as to determine the therapeutic targets.

Esophageal foreign bodies: 177 cases.

The aim of this study is to assess patients treated for esophageal foreign bodies. The charts of patients (n=177), between January 1994 and April 2009, were investigated retrospectively. Patients' age and gender, locations and types of foreign bodies (FBs) and interventions were taken into consideration.

Evaluation of two-center Coulomb and hybrid integrals over complete orthonormal sets of Ψα-ETO using auxiliary functions.

By the use of ellipsoidal coordinates, the two-center Coulomb and hybrid integrals over complete orthonormal sets of Ψα-ETO exponential type orbitals arising in ab initio calculations of molecules are evaluated, where α = 1,0, -1, -2, ...

A novel and one-pot synthesis of new 1-tosyl pyrrol-2-one derivatives and analysis of carbonic anhydrase inhibitory potencies.

Here we propose a novel one-pot synthesis of new tosyl-pyrrole derivatives. By means of the new developed method, pyrrole derivatives were synthesized at room temperature in a single step, and a useful method is proposed for the synthesis of similar compounds. Moreover, inhibitions of two human cytosolic carbonic anhydrase (hCA, EC 4.

PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas.

A hallmark feature of glioblastoma is its strong self-renewal potential and immature differentiation state, which contributes to its plasticity and therapeutic resistance. Here, integrated genomic and biological analyses identified PLAGL2 as a potent protooncogene targeted for amplification/gain in malignant gliomas. Enhanced PLAGL2 expression strongly suppresses neural stem cell (NSC) and glioma-initiating cell differentiation while promoting their self-renewal capacity upon differentiation induction.

Linking functional decline of telomeres, mitochondria and stem cells during ageing.

The study of human genetic disorders and mutant mouse models has provided evidence that genome maintenance mechanisms, DNA damage signalling and metabolic regulation cooperate to drive the ageing process. In particular, age-associated telomere damage, diminution of telomere 'capping' function and associated p53 activation have emerged as prime instigators of a functional decline of tissue stem cells and of mitochondrial dysfunction that adversely affect renewal and bioenergetic support in diverse tissues. Constructing a model of how telomeres, stem cells and mitochondria interact with key molecules governing genome integrity, 'stemness' and metabolism provides a framework for how diverse factors contribute to ageing and age-related disorders.

Synthesis and antioxidant properties of diphenylmethane derivative bromophenols including a natural product.

Bromination of bis(3,4-dimethoxyphenyl)methanone (5) gave four products (6-9) with mono, di, tri, and tetra Br under different conditions. Reduction and demethylation reactions of product 9 with tetra Br were performed, consecutively and a natural product, 5,5'-methylene bis(3,4-dibrombenzene-1,2-diol) (1), was obtained with a 53% yield. Five derivatives, (13-17) (bromophenols), of 1 were also synthesised.

2,3-Dibromo-1-[4-(2,3-dibromo-4,5-di-meth-oxy-benz-yl)-2,5-dimeth-oxy-benz-yl]-4,5-dimeth-oxy-benzene.

The mol-ecule of the title compound, C(26)H(26)Br(4)O(6), is located around a crystallographic inversion center. The dihedral angle between the central benzene ring and the outer benzene ring is 89.26 (1)°.

3-Phenyl-diazen-yl-1,2-dimethyl-1H-indole.

In the title mol-ecule, C(16)H(15)N(3), the indole ring system is planar within 0.021 (3) Å and the phenyl ring is inclined to this plane by 17.32 (14)°.

2-Ethyl-6,6-ethyl-enedisulfanediyl-7-methoxy-methyl-1,2,3,4,5,6-hexa-hydro-1,5-methano-azocino[4,3-b]indol-3-one.

The title compound, C(20)H(24)N(2)O(2)S(2), consists of a tetra-cyclic ring system containing an azocino skeleton with ethyl, dithiol-ane and methoxy-methyl groups as substituents. The benzene and five-membered rings are nearly coplanar, with a dihedral angle of 2.78 (11)°.