Focused Fluorescent Probe Library for Metal Cations and Biological Anions

A focused fluorescent probe library for metal cations was developed by combining metal chelators and picolinium/quinolinium moieties as combinatorial blocks connected through a styryl group. Furthermore, metal complexes derived from metal chelators having high binding affinities for metal cations were used to construct a focused probe library for phosphorylated biomolecules. More than 250 fluorescent probes were screened for identifying an ultraselective probe for dTTP

Correction to Focused Fluorescent Probe Library for Metal Cations and Biological Anions

Correction to Focused Fluorescent Probe Library for Metal Cations and Biological Anion

Southern blot analysis of telomere lengths of nucleus pulposus chondrocytes derived from two donors of different ages during multiple passages.

<p>There was a steady decline in telomere length with advancing passage number, irrespective of age (Kb, kilobases; M, marker; CTL, control; P, passage).</p

Correlation analysis of cumulative population doubling level (PDL) of nucleus pulposus chondrocytes versus (A) donor age, (B) initial telomere length, and (C) initial telomerase activity.

<p>Telomere length and telomerase activity at the first passage are indicated as initial telomere length and initial telomerase activity. Telomere lengths are provided in kilobases (kb) and the level of telomerase activity as relative telomerase activity (RTA).</p

Summary of the characteristics of nucleus pulposus tissues obtained from patients: cumulative population doubling level, initial telomere length, and initial telomerase activity of nucleus pulposus chondrocytes.

<p>Summary of the characteristics of nucleus pulposus tissues obtained from patients: cumulative population doubling level, initial telomere length, and initial telomerase activity of nucleus pulposus chondrocytes.</p

Changes in telomere length and telomerase activity of nucleus pulposus chondrocytes (NPCs) during long-term culture.

<p>Both (A) telomere length and (B) telomerase activity of NPCs exhibited a steady decline with advancing population doubling. Telomere lengths are provided in kilobases (kb) and the level of telomerase activity as relative telomerase activity (RTA).</p

Association between SLE and thyroid disease.

<p>Association between SLE and thyroid disease.</p

Descriptive characteristics of the study population.

<p>Descriptive characteristics of the study population.</p

Analyses stratified according to age and sex for evaluating the association between SLE and thyroid disease.

<p>^aAdjusted for age. ^bAdjusted for sex. ^cAdjusted for age and sex.</p

Table1_Metformin acts as a dual glucose regulator in mouse brain.DOCX

Aims: Metformin improves glucose regulation through various mechanisms in the periphery. Our previous study revealed that oral intake of metformin activates several brain regions, including the hypothalamus, and directly activates hypothalamic S6 kinase in mice. In this study, we aimed to identify the direct effects of metformin on glucose regulation in the brain.Materials and methods: We investigated the role of metformin in peripheral glucose regulation by directly administering metformin intracerebroventricularly in mice. The effect of centrally administered metformin (central metformin) on peripheral glucose regulation was evaluated by oral or intraperitoneal glucose, insulin, and pyruvate tolerance tests. Hepatic gluconeogenesis and gastric emptying were assessed to elucidate the underlying mechanisms. Liver-specific and systemic sympathetic denervation were performed.Results: Central metformin improved the glycemic response to oral glucose load in mice compared to that in the control group, and worsened the response to intraperitoneal glucose load, indicating its dual role in peripheral glucose regulation. It lowered the ability of insulin to decrease serum glucose levels and worsened the glycemic response to pyruvate load relative to the control group. Furthermore, it increased the expression of hepatic G6pc and decreased the phosphorylation of STAT3, suggesting that central metformin increased hepatic glucose production. The effect was mediated by sympathetic nervous system activation. In contrast, it induced a significant delay in gastric emptying in mice, suggesting its potent role in suppressing intestinal glucose absorption.Conclusion: Central metformin improves glucose tolerance by delaying gastric emptying through the brain-gut axis, but at the same time worsens it by increasing hepatic glucose production via the brain-liver axis. However, with its ordinary intake, central metformin may effectively enhance its glucose-lowering effect through the brain-gut axis, which could surpass its effect on glucose regulation via the brain-liver axis.</p