Rewired Cellular Metabolic Profiles in Response to Metformin under Different Oxygen and Nutrient Conditions

Metformin is a metabolic disruptor, and its efficacy and effects on metabolic profiles under different oxygen and nutrient conditions remain unclear. Therefore, the present study examined the effects of metformin on cell growth, the metabolic activities and consumption of glucose, glutamine, and pyruvate, and the intracellular ratio of nicotinamide adenine dinucleotide (NAD⁺) and reduced nicotinamide adenine dinucleotide (NADH) under normoxic (21% O₂) and hypoxic (1% O₂) conditions. The efficacy of metformin with nutrient removal from culture media was also investigated. The results obtained show that the efficacy of metformin was closely associated with cell types and environmental factors. Acute exposure to metformin had no effect on lactate production from glucose, glutamine, or pyruvate, whereas long-term exposure to metformin increased the consumption of glucose and pyruvate and the production of lactate in the culture media of HeLa and HaCaT cells as well as the metabolic activity of glucose. The NAD⁺/NADH ratio decreased during growth with metformin regardless of its efficacy. Furthermore, the inhibitory effects of metformin were enhanced in all cell lines following the removal of glucose or pyruvate from culture media. Collectively, the present results reveal that metformin efficacy may be regulated by oxygen conditions and nutrient availability, and indicate the potential of the metabolic switch induced by metformin as combinational therapy.     

Mechanism of the Photofading of Stilbene–fluorescent Dyes. Contribution of Singlet Oxygen to the Photofading of 4, 4‘–Bisacetamidostilbene

Self—sensitized and Rose Bengal—sensitized photo—oxidation of 4, 4′-bisacetamidostilbene (BAAS) in solution gives p—acetamidobenzaldehyde and p—acetamidobenzoic acid via the reaction of singlet oxygen with the trans isomer (la). The rate of the photo—oxidation is retarded in the presence of effective singlet oxygen quenchers. On the other hand, cls—BAAS (lb) is more stable to visible light under the conditions of Rose Bengal—sensitized photo—oxidation than trans—stilbene.     

n-Hexyl Laurate and Fourteen Related Fatty Acid Esters: New Secretory Compounds from the Julid Millipede, Anaulaciulus sp.

A total of fifteen saturated fatty acid esters were newly identified from the secretions of an unidentified Anaulaciulus sp. (Julida: Julidae). The fatty acid components of the esters were composed of normal chain acids (from C₁₀ to C₁₄) and of branched chain acids (from iso-C₁₂ to iso-C₁₅ and anteiso-C₁₅). The alcohol moieties were all composed of normal chain alcohols varying from n-butanol to n-octanol. The most abundant component found in the total esters was n-hexyl laurate (64.7%). Novel compounds identified from the millipede secretion extracts include six branched iso- and anteiso-fatty esters, an odd-numbered C₁₁-fatty acid ester, a C₁₃-fatty acid ester, and a C₇-alcohol ester, all of which were previously undescribed natural products. In addition, a characteristic mixture of benzoquinones, such as 2-methyl-1,4-benzoquinone, 2-methoxy-3-methyl-1,4-benzoquinone, 2,3-dimethoxy-1,4-benzoquinone, 2-methoxy-6-methyl-1,4-benzoquinone, and 2,3-dimethoxy-5-methyl-1,4-benzoquinone were identified from the secretions, together with trace amounts of 1,4-benzoquinone.     

Mechanisms Underlying Decreased Hepatic Triacylglycerol and Cholesterol by Dietary Bitter Melon Extract in the Rat

In these studies, we focused on finding the mechanism(s) underlying the bitter melon (Momordica charantia L.) methanol fraction (MF)-dependent reduction in the concentration of hepatic triacylglycerol (TAG) and cholesterol in the rat. Rats were fed diets containing low (5 %) fat for 2 weeks (experiment 1), or low (5 %) and high (15 %) fat for a longer period of 8 weeks (experiment 2). MF was supplemented at 1 % level in both experiments. After feeding, rats were sacrificed, and their livers were prepared as slices and hepatocytes, followed by incubation with [1(2)-¹⁴C] acetate or [1-¹⁴C] oleic acid (18:1 n-6). Under these conditions, we found that rats fed diets containing MF, as compared to those without MF, showed: (1) no adverse effects on food intake and growth, (2) a decreased hepatic TAG and total cholesterol, irrespective of the difference in dietary fat level or feeding period, and (3) a decreased incorporation of [1(2)-¹⁴C] acetate and [1-¹⁴C] oleic acid into TAG of liver slices and hepatocytes. MF-supplemented rats also showed no altered incorporation of labeled acetate into cholesterol and cholesterol ester, an increased fecal excretion of neutral steroids, but not of acidic steroids, and an enhanced mRNA abundance of carnitine palmitoylacyltransferase I, which is the rate-limiting enzyme for fatty acid oxidation. These results suggest that dietary MF decreases hepatic TAG synthesis while enhancing fatty acid oxidation, thereby reducing the concentration of hepatic TAG. The liver cholesterol-lowering effect of MF, however, is probably mediated through an increased fecal excretion of neutral steroids, without an effect on cholesterogenesis.     

Synthesis and optical properties of the [2.2]paracyclophane-containing π-conjugated polymer with a diacetylene unit

Summary Novel through-spaceπ-conjugated polymer based on poly(p-henyleneethynylene)/poly(p-phenylenebutadiynylene) hybrids containing a [2.2]paracyclophane unit in the main chain was synthesized by copper-catalyzed alkyne coupling reaction. The structure of the polymer was supported by ¹H NMR and IR spectra. The obtained polymer was soluble in common organic solvents such as THF, CH₂C1₂, CHC1₃ and toluene. The number-average of molecular weight of the polymer was estimated to be 63000 by GPC. The polymer emitted a bluish green light in solution and in the solid state. Received:24 September 2002/Revised version: 19 November 2002/Accepted: 19 November 2002 Correspondence to Yoshiki Chujo     

Synthesis and properties of conjugated copolymers having a tricarbonyl(arene)chromium and thiophene units in the main chain

Summary Palladium-catalyzed polymerization of η ⁶-(1,4-diethynylbenzene)tricarbonyl chromium (1) with 3-alkyl-2,5-dibromothiophene (2a-c) was carried out to give the corresponding alternating conjugated copolymers (5a-c) in good yields. The structures of the polymers were supported by ¹H NMR and IR spectra. The polymers obtained were soluble in common solvents such as THF, CH₂Cl₂, CHCl₃ and toluene. The molecular weights of the polymers were determined by GPC. Their thermal, optical and electrical properties were investigated in detail. Received: 18 March 2002 /Accepted: 1 April 2002     

Synthesis and Properties of Novel Poly(p-phenylenevinylene)s Containing a Tricarbonyl(arene)chromium Unit in the Main Chain

Summary Novel π-conjugated polymers based on poly(p-phenylenevinylene)s (PPVs) containing a tricarbonyl(arene)chromium unit in the main chain were synthesized by Horner-Wadsworth-Emmons olefination. The structures of the polymers were supported by ^lH NMR and IR spectra. The polymers obtained were soluble in common solvents such as THF, CH₂Cl₂, CHCl₃ and toluene. The molecular weights of the polymers were determined by GPC. Their thermal, optical, and electrochemical properties were investigated in detail. Received: 18 November 2002/Revised version: 10 February 2003/ Accepted: 11 February 2003 Correspondence to Yoshiki Chujo     

A comparative study on the thermally enhanced reorientation between random and diblock methacrylate copolymers with photo-cross-linkable mesogenic side groups by irradiating with linearly polarized ultraviolet light

The thermally enhanced photoinduced reorientation behavior of random and diblock copolymer films of methyl methacrylate and methacrylate with a photo-cross-linkable 4-(4-methoxycinnamoyloxy)biphenyl (MCB) side groups was investigated by irradiating with linearly polarized ultraviolet light and subsequently annealing. Random copolymers were synthesized by free radical copolymerization, while diblock ones were obtained by an atom transfer radical polymerization method with a PMMA macroinitiator. The photoinduced optical anisotropy was thermally amplified when the copolymer exhibited a liquid crystalline phase. The random copolymers with a high composition of MCB side groups reverted the orientation direction and inhibited molecular aggregation. For the diblock copolymers, the reorientation behavior was analogous to the methacrylate homopolymer with MCB side groups and transmission electron microscopy revealed a phase separation structure with molecular orientation of the MCB groups.     

Local Dynamics of Adhesives in Aggressive Environment in the Pre-Damage Stage

Molecular aspects of chemical and physical changes in adhesive joints caused by absorbed moisture were investigated. The focus was on the pre-damage stage that precedes the formation of voids and microcracks. A model and a commercial epoxy-amine formulation were studied. Local dynamics were monitored by broad-band dielectric relaxation spectroscopy (DRS). One portion of the absorbed water does not form hydrogen bonds with the network and gives rise to a fast relaxation process (termed γ) with activation energy of 28 kJ/mol. The local β dynamics are slowed down by the interactions between water and various sites on the network that include the ether oxygen, the hydroxyl group and the tertiary amine nitrogen. One particularly significant finding is that the average relaxation time for the β process above 20°C is of the order of nanoseconds or less and, hence, the detection and monitoring of this process hinges upon the ability to perform high-precision DRS at frequencies above 1 MHz. This is an important consideration in the ongoing efforts aimed at the implementation of DRS as nondestructive inspection (NDI) tool for adhesive joints.