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Articles by M Ma
Total Records ( 3 ) for M Ma
  Y Ma , M Ma , Y Dai and A. Hong

The development of rBAY, a recombinant peptide with the similar sequence of synthetic BAY55-9837, as a potential peptide therapeutic for type 2 diabetes is still a challenge mainly because of its poor stability in aqueous solution. To improve the peptide stability and bioactivity and investigate its biological effects for VPAC2-specific activation, RBAYL with 31 aa was designed based on sequence alignments of pituitary adenylate cyclase-activating peptides (PACAPs), vasoactive intestinal peptide (VIP), and related analogs and generated through site-directed mutagenesis. Stability analysis showed that the prepared RBAYL with three mutations (N9Q, V17L, and N28K) were much more stable than rBAY. rRBAYL (the recombinant RBAYL) was expressed and purified by gene-recombination technology via native thiol ligation on solid beads. As much as 27.7 mg rRBAYL peptide with purity over 98% was obtained from 1 L of LB medium without expensive high-performance liquid chromatography refinements. The bioactivity assay of rRBAYL showed that it displaced [125I]PACAP38 and [125I]VIP from VPAC2 with a half-maximal inhibitory concentration of 51 ± 6 and 50 ± 4 nM, respectively, which were similar to those of the chemically synthesized RBAYL (sRBAYL) and lower than those of Ro25-1553, an established VPAC2 agonist. rRBAYL enhances the cAMP accumulation in CHO cells expressing human VPAC2 with a half-maximal stimulatory concentration (EC50) of 0.91 nM, whereas the receptor potency of rRBAYL at human VPAC1 (EC50 of 719 nM) was only 1/790 of that at human VPAC2, and rRBAYL had no activity toward human PAC1 receptor. Western-blot assay for glucose transporter 4 (GLUT4) indicated that the rRBAYL could significantly induce GLUT4 expression more efficiently than rBAY or Ro25-1553 in adipocytes. Compared with rBAY, rRBAYL can more efficiently promote insulin release and decrease plasma glucose level in ICR mice. Our results suggested that rRBAYL is a novel recombinant VPAC2-specific agonist with high stability and bioactivity.

  Y Liao , J Tang , M Ma , Z Wu , M Yang , X Wang , T Liu , X Chen , P. C Fletcher and W. Hao

Ketamine abuse has been shown to have a deleterious impact on brain function. However, the precise mechanisms of ketamine dependence-induced pathological change remain poorly understood. Although there is evidence for white matter changes in drug abuse, the presence of white matter abnormalities in chronic ketamine users has not been studied. White matter volumes were measured using in vivo diffusion tensor magnetic resonance imaging data in 41 ketamine-dependent subjects and 44 drug-free healthy volunteers. White matter changes associated with chronic ketamine use were found in bilateral frontal and left temporoparietal cortices. There was also evidence that frontal white matter fractional anisotropy correlated with the severity of drug use (as measured by estimated total ketamine consumption). We provide direct evidence for dose-dependent abnormalities of white matter in bilateral frontal and left temporoparietal regions following chronic ketamine use. The findings suggest a microstructural basis for the changes in cognition and experience observed with prolonged ketamine use. Moreover, the similarities of these changes to those observed in chronic schizophrenia have implications for the glutamate model of this illness.

  A Savigner , P Duchamp Viret , X Grosmaitre , M Chaput , S Garcia , M Ma and B. Palouzier Paulignan

In mammals, the sense of smell is modulated by the status of satiety, which is mainly signaled by blood-circulating peptide hormones. However, the underlying mechanisms linking olfaction and food intake are poorly understood. Here we investigated the effects of two anorectic peptides, insulin and leptin, on the functional properties of olfactory sensory neurons (OSNs). Using patch-clamp recordings, we analyzed the spontaneous activity of rat OSNs in an in vitro intact epithelium preparation. Bath perfusion of insulin and leptin significantly increased the spontaneous firing frequency in 91.7% (n = 24) and 75.0% (n = 24) of the cells, respectively. When the activity was electrically evoked, both peptides shortened the latency to the first action potential by ~25% and decreased the interspike intervals by ~13%. While insulin and leptin enhanced the electrical excitability of OSNs in the absence of odorants, they surprisingly reduced the odorant-induced activity in the olfactory epithelium. Insulin and leptin decreased the peak amplitudes of isoamyl acetate-induced electroolfactogram (EOG) signals to 46 and 38%, respectively. When measured in individual cells by patch-clamp recordings, insulin and leptin decreased odorant-induced transduction currents and receptor potentials. Therefore by increasing the spontaneous activity but reducing the odorant-induced activity of OSNs, an elevated insulin and leptin level (such as after a meal) may result in a decreased global signal-to-noise ratio in the olfactory epithelium, which matches the smell ability to the satiety status.

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