β-Actin Peptide-Based Inhibitors of Histidine Methyltransferase SETD3

SETD3 was recently identified as the histidine methyltransferase responsible for N³-methylation of His73 of β-actin in humans. Overexpression of SETD3 is associated with several diseases, including breast cancer. Here, we report a development of actin-based peptidomimetics as inhibitors of recombinantly expressed human SETD3. Substitution of His73 by simple natural and unnatural amino acids led to selected β-actin peptides with high potency against SETD3 in MALDI-TOF MS assays. The selenomethionine-containing β-actin peptide was found to be the most potent SETD3 inhibitor (IC₅₀=161 nM). Supporting our inhibition assays, a combination of computational docking and molecular dynamics simulations revealed that the His73 binding pocket for β-actin in SETD3 is rigid and accommodates the inhibitor peptides with similar binding modes. Collectively, our work demonstrates that actin-based peptidomimetics can act as potent SETD3 inhibitors and provide a basis for further development of highly potent and selective inhibitors of SETD3.     

The Role of Catalysis in Determining Men’s Quality of Life

Modern civilization, whose spectacular development took place in the second half of XX century as the result of scientific and information revolution has six characteristic features: (1) it is a mass civilization, (2) it is mobile, (3) it is global, (4) it is free of the spectre of famine, (5) it is built on informatics, (6) human lifespan is steadily prolonged. In order to achieve these goals it was necessary to invent thousands new materials and to find out methods of their fast and cheap production in large quantities. The unique possibility of the fast and selective production of the desired chemical molecules, required to obtain a material with defined properties, is offered by catalysis. Catalysis comprises technological processes of the largest scale, such as catalytic cracking of billions tons of crude oil per year and smallest scale enzymatic reactions with micrograms of product formed with 100% chemo-, regio- and stereoselectivity. With the rapidly growing earth’s population increasingly important becomes not only the production of materials needed in our modern society, but also the destruction of undesired by-products of its activities, making the application of catalysis to pollution control one of important tasks. The progress of catalysis, both science and technology, was in the last 50 years driven by the development in five fields: (1) new materials, particularly those based on the principle of molecular imprinting (use of templates), (2) application of new surface science techniques to identify active sites and surface reaction intermediates, (3) quantum chemical modeling of elementary steps of catalytic reactions, (4) design of new reactors, (5) development of computational catalysis, (6) development of new ways for carrying catalytic reactions, (7) biocatalysis using enzymes, modified by mutagenesis and recombination techniques to make them selective and active in conditions of the desired technological process. Application of molecular sieves, catalytic antibodies, metallocene catalysts, asymmetric catalysis, fuel cells, control of automotive exhaust are described and pending change of the paradigm of catalysis is discussed.     

The Role of E3 Ubiquitin Ligase Cbl Proteins in β-Elemene Reversing Multi-Drug Resistance of Human Gastric Adenocarcinoma Cells

Recent studies indicate that β-elemene, a compound isolated from the Chinese herbal medicine Curcuma wenyujin, is capable of reversing tumor MDR, although the mechanism remains elusive. In this study, β-Elemene treatment markedly increased the intracellular accumulation of doxorubicin (DOX) and rhodamine 123 in both K562/DNR and SGC7901/ADR cells and significantly inhibited the expression of P-gp. Treatment of SGC7901/ADR cells with β-elemene led to downregulation of Akt phosphorylation and significant upregulation of the E3 ubiquitin ligases, c-Cbl and Cbl-b. Importantly, β-elemene significantly enhanced the anti-tumor activity of DOX in nude mice bearing SGC7901/ADR xenografts. Taken together, our results suggest that β-elemene may target P-gp-overexpressing leukemia and gastric cancer cells to enhance the efficacy of DOX treatment.     

The Effect of Cobalt on the Degradation of Methyl β-D-Gluco-Pyranoside by Oxygen in Aqueous Sodium Hydroxide Solution

Abstract

The effect of Co(II) (0 to 0.25 mW CoSO₄) on the degradation of methyl β-D-glucopyranoside (MBG) at 120°C in 1.25M NaOH with 0.68 MPa oxygen pressure was studied. When the Co(II) was increased from 0.00 to 0.01 to 0.05 mM the MBG half-life decreased from 12 to 6 to 1.5 hours, reflecting approximately a 0.5 order kinetic dependence on cobalt. An oxidation-reduction cycle between Co(II) and Co(III) involving oxidation of Co(II) by oxygen and oxidation of the glucoside by Co(III), hydroxyl radical, or superoxide is proposed for the degradation. At the 0.25 mM Co(II) addition level highly adsorptive Co(OH)₂ formed prior to reaction initiation with oxygen and removed otherwise soluble cobalt from solution. This resulted in lower rates of MBG degradation than obtained even at 0.01 mM Co(II) addition. However, Co(II) solubility could be enhanced if silicate anions or polyols (including MBG) were added to the alklaine medium prior to the Co(II) addition. In reactions initially containing 0.25 mM soluble Co(II), an adsorptive precipitate, presumably CoO(OH), gradually formed after reaction initiation with oxygen. Precipitation of the Co(III) solid coincided with a rapid decline in the rate of MBG degradation. Cobalt had little effect on the products of MBG degradation.     

Effect of β-Si3N4 starting powder size on elongated grain growth in β-Si3N4 ceramics

The microstructural evolution of pressureless sintered silicon nitride ceramics prepared from different particle sizes of β-Si₃N₄ as starting powders, has been investigated. When the specimen prepared from as-received β-powder of 0.66 μm in average size, was sintered at 1850°C, equiaxed β-Si₃N₄ grains were observed. As the size of the initial β-powder went down to 0.26 μm, however, the growth of elongated grains was enhanced, which resulted in a whisker-like microstructure similar to that made from α-starting powder. When the sintering temperature was increased to 2000°C, the elongated grains were also developed even in the specimen made from 0.66 μm β-powder. The observed results were discussed with relation to the two dimensional nucleation and growth theory for faceted crystals. In addition, fracture toughness of the specimen consisting of elongated grains, which was prepared from finer powders, increased.     

The Role of the Liquid‐Solid Interface in the Preparation of Supported Catalysts

The contribution of the Interface Science to the preparation of supported catalysts during the last two decades is presented. It is illustrated how the concepts and the methodologies of the Interface Science could be effectively used for an in‐depth understanding of the phenomena involved in the initial preparation step. This, extremely critical step, concerns the deposition of transition metal species containing the active elements, from an impregnation solution, onto the surface of common catalytic supports. Moreover, the aforementioned concepts and methodologies allow the regulation of the mode of interfacial deposition and the local structure of the deposited species and, thus, the surface characteristics and the catalytic behaviour of the resulted catalysts.     

The effect of CaO on the physicochemical and biological properties of β-SiAlON ceramics

To investigate the effects of CaO on the physicochemical and biological properties of β-SiAlON, β-SiAlON ceramics containing CaO were prepared using the direct nitriding method. The results of X-ray powder diffraction and scanning electron microscopy demonstrated that β-SiAlON remained in the material phase because the addition of Ca did not result in the formation of Ca-α-SiAlON. However, CaO promoted the sintering of β-SiAlON grains and significantly decreased porosity and increased bulk density and compressive strength. According to a chemical stability study, when β-SiAlON ceramics powder was soaked in deionized water and a cell culture medium, it was noted to have negative electricity. A reaction occurred with the H⁺ and OH⁻ ions in the deionized water, leading to the formation of surface structures, such as Si-OH, Al-OH, and N-H. Moreover, the addition of CaO caused a different chemical reaction among ions or ion groups in the culture medium, and new chemical groups formed on the material surface that interacted with the culture medium, which resulted in an alteration of the zeta potential and surface chemical properties of β-SiAlON. MC3T3-E1 cells cultured on the surface of ceramics proved that the cells cannot adhere well to the surface of β-SiAlON ceramics with CaO, although they could proliferate well around those with only β-SiAlON. Therefore, the change in the surface chemical properties provides good anticell adhesion ability, which makes β-SiAlON with CaO a biocompatible material that can be used to prevent contamination caused by cell adhesion, with possible applications in biosensors or biomedical equipment that must be used in sterile environments.     

The effect of mass transfer on reaction rates during immobilized β-galactosidase-catalyzed conversion of lactose in hollow fiber membrane

The mass transfer of substrates through a bio-catalytic membrane layer is a key issue in determining the performance of β-galactosidase-catalyzed conversion of lactose in a hollow fiber membrane reactor (HFMR) system. An investigation on the effect of solutes mass transfer through a bio-catalytic membrane layer was carried out using the coupled mass transfer-reaction model. Product formation was reduced at a trans-membrane pressure (TMP) of higher than 0.5?bar. Meanwhile, the concentration polarization modulus of solutes rapidly increased with higher TMP and this result suggests the formation of gel layer, which reduced bio-catalysis rate at higher applied TMP. The concentration profile of solutes or substrates on the bio-catalytic membrane surface, which determines the rate of reaction was reduced due to mass transfer limitation. This investigation highlights that the formation of substrate-β-gal complex in an immobilized system is influenced by the mass transfer behavior of its substrate.     

The Role of PPARα in Metformin-Induced Attenuation of Mitochondrial Dysfunction in Acute Cardiac Ischemia/Reperfusion in Rats

Metformin, an anti-diabetic drug, exerts cardioprotection against ischemia-reperfusion (IR) through the activation of AMPK. However, the molecular mechanisms underlying these beneficial effects remain elusive. In this study, we examined the role of PPARα in mediating cardioprotective effects of metformin on mitochondria. Hearts of male Sprague-Dawley rats perfused by Langendorff were subjected to IR in the presence or absence of metformin and the PPARβ inhibitor, GW6471. IR reduced cardiac function and compromised the structural integrity of cardiac cells evidenced by increased LDH release from the hearts. In addition, IR induced mitochondrial dysfunction as evidenced by reduced respiration and increased mitochondrial permeability transition pore (PTP) opening. However, metformin-treated hearts demonstrated improved post-ischemic recovery of cardiac function and reduced cell death that were associated with increased state 3 respiration at complexes I and II (by 27% and 32%, respectively, both p < 0.05) and decreased PTP opening (by 27%, p < 0.05) compared to untreated hearts. The protective effects of metformin on cardiac function and mitochondria were blocked by GW6471. Thus, our results demonstrate that inhibition of PPARα attenuates the beneficial effects of metformin on mitochondria in acute IR.     

Effect of the addition of β-Si3N4 nuclei on the thermal conductivity of β-Si3N4 ceramics

Various microstructures of β-Si₃N₄ were fabricated, with or without the addition of β-Si₃N₄ seed particles to high-purity β-Si₃N₄ powder, using Yb₂O₃ and ZrO₂ as sintering additives, by gas-pressure sintering at 1950 °C for 16 h. The thermal conductivity of the specimen without seeds was 140 W·(m·K)⁻¹, and the specimen exhibited a bimodal microstructure with abnormally grown grains. The thermal conductivity of the specimen with 24 vol.% seed addition was 143 W·(m·K)⁻¹, and this specimen had the bimodal microstructure with finer grain size than that without the seeded material, but maintained the same amount of large grains (⩾2 μm in diameter) as in the specimen without the seeds. This finding indicates that the thermal conductivity of β-Si₃N₄ is controlled by the amount of reprecipitated large grains, rather than by the grain size of the β-Si₃N₄.     

The influence of hydrogen pressure on the heterogeneous hydrogenation of β-myrcene in a CO2-expanded liquid

This paper presents the second part of work on the effect of hydrogen partial pressure on the hydrogenation of a terpene in a CO₂-expanded liquid. The effect of hydrogen partial pressure on the hydrogenation of β-myrcene possessing three CC bonds catalysed by alumina-supported ruthenium and rhodium was studied. Experiments were performed at various hydrogen pressures in the range from 2.0 up to 4.5 MPa at a fixed total pressure of 12.5 MPa. In all the conditions the reaction proceeded in two phases (liquid + gas), that is, the total pressure was below the critical pressure of the CO₂ + β-myrcene + H₂ system. The liquid phase volume is expanded in relation to the initial volume of β-myrcene in a fashion that is strongly dependent on the hydrogen and carbon dioxide pressures. An increase of H₂ pressure concomitantly diminishes carbon dioxide pressure, which leads to the enhancement of the liquid phase in hydrogen and a terpene. It does not direct to straightforward higher reaction rate, but surprisingly the effect of higher concentrations either hydrogen or β-myrcene is opposite. It is attributed to the fact that the hydrogenation of β-myrcene rate-controlling factor turns out to be the hydrogen to β-myrcene ratio which decreases as the hydrogen pressure increases. These unexpected appealing results present that lower pressures of hydrogen guide to higher hydrogen/β-myrcene ratios in the liquid phase, but on the other hand they also amplify the initial reaction rate constant. The obtained results are opposite to the results achieved for effect of hydrogen pressure on the Pd-catalysed hydrogenation of limonene consisting of two CC double bonds.     

Effect of large β-Si3N4 particles on the thermal conductivity of β-Si3N4 ceramics

Mean-field micromechanics model, the rule of mixture is applied to the prediction of the thermal conductivity of sintered β-Si₃N₄, considering that the microstructure of β-Si₃N₄ is composed of a uniform matrix phase (which contains grain boundaries and small grains of Si₃N₄) and the purified large grains (⩾2 μm in diameter) of Si₃N₄. Experimental results and theoretical calculations showed that the thermal conductivity of Si₃N₄ is controlled by the amount of the purified large grains of Si₃N₄. The present study demonstrates that the high thermal conductivity of β-Si₃N₄ can be explained by the precipitation of high purity grains of β-Si₃N₄ from liquid phase.     

The effect of Ag nanoparticles content on dielectric and microwave absorption properties of β-SiC

In the present work, high purity cubic silicon carbide (β-SiC) was synthesized by using resorcinol-formaldehyde aerogel coated silica as precursor at high temperature. Subsequently, β-SiC was coated with various concentrations of silver nanoparticles (Ag NPs) by tin sensitization electroless plating. Thereafter, the effect of various Ag NPs contents on the dielectric and microwave absorption properties of β-SiC was investigated in detailed. It is found that the Ag NPs can significantly increase the overall complex permittivity, reduce the thickness of the absorber and increase the absorption bandwidth to some extent. Despite, the improvement of the attenuation ability of electromagnetic wave with increasing contents of Ag NPs also has an adverse effect on impedance matching. The improvement in the microwave absorption of β-SiC coated with Ag NPs mainly comes from the enhancement of dipole polarization, interface polarization and conductivity loss. In the 2–18 GHz band, Ag@SiC (1.0 g/L) can achieve an effective bandwidth of 4.99 GHz at a thickness of 1.6 mm, and it is a kind of lightweight, high-temperature microwave absorbent with excellent performance.     

The effect of soluble β-nucleator's content on crystalline structure and performance of polypropylene pipe

Strength-toughness clash of polypropylene (PP) pipe is an insurmountable bottleneck for the potential application. Here, we successfully prepared PP pipe with simultaneously enhanced toughness and hoop strength via addition of soluble β-nucleators (β-NAs) and application of helical flow in the extrusion. The outstanding combination of strength and toughness in the PP pipe depended on the loading content of β-NAs and the helical pattern, which determined the morphology and alignment of β-crystals. At the low content, β-NAs dissolved completely into the PP melts and distributed homogeneously to promote the formation of β-spherulites in the PP pipe. When the loading content exceeded the solubility limit, the β-NAs partially dissolved and upon cooling, the dissolved β-NAs grew preferentially on the undissolved ones along one direction, assembling into the fibrous aggregates. With the guidance of helical flow, the fibrous β-NAs aligned off the axis and functioned as an oriented template to trigger the PP crystallization on the surface into hybrid β-shish-kebab with fibrous β-NAs as shish. Increasing rotation speed of mandrel and die elevated hoop contribution to obtain the β-shish-kebab with a deviated angle of 55°, endowing the prepared pipe with high hoop strength and toughness.     

The Role of Lignin in Surface-Activated Bonding of Lignocellulose—Characterized by Differential Scanning Calorimetryt

The study of surface modification to prepare an optimum surface for bonding is of practical importance for the production of glued materials. Lignocellulosic materials contain many chemical groupings such as phenolic and alcoholic hydroxyls, carbonyl groups, etc., capable of being readily activated by physical or chemical methods. These active sites can then react under heat and pressure, either with active sites from another surface, or through a crosslinking agent to form a glued product.

This paper reports the role of lignin in the reactions between lignocellulosic materials and hydrogen peroxide studied by a differential scanning calorimetry method. The results showed that lignin is much more reactive toward hydrogen peroxide than is cellulose, and that the lignin-hydrogen peroxide reaction yields the highest enthalpy. Correlation between lignin and enthalpy, and enthalpy and bonding will also be discussed.     

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.     

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.