Comparison of preference-based health-related quality of life measures for chronic neck pain: a pooled analysis of data from three RCTs.

Objectives: This study aimed to identify a preference-based health-related quality of life (HRQOL) measure that best reflects disease-specific features in patients with neck pain by comparing the characteristics of the instruments.

Design: Pooled data from three multicentre randomised controlled clinical trials (RCTs) on neck pain were included for analysis in this study.

Setting: All three RCTs were conducted between 2017 and 2020 in Korea, and patients were recruited from four hospitals and one university teaching hospital.

Restoring social deficits in IRSp53-deleted mice: chemogenetic inhibition of ventral dentate gyrus Emx1-expressing cells.

IRSp53 is a synaptic scaffold protein reported to be involved in schizophrenia, autism spectrum disorders, and social deficits in knockout mice. Identifying critical brain regions and cells related to IRSp53 deletion is expected to be of great help in the treatment of psychiatric problems. In this study, we performed chemogenetic inhibition within the ventral dentate gyrus (vDG) of mice with IRSp53 deletion in Emx1-expressing cells (Emx1-Cre;IRSp53 flox/flox).

In Vivo Contribution of Cyp24a1 Promoter Vitamin D Response Elements.

CYP24A1 is a multifunctional, P450 mitochondrial enzyme that catabolizes the vitamin D hormone (calcitriol, 1,25(OH)2D3), its precursor (calcifediol, 25(OH)D3), and numerous vitamin D metabolites. In the kidney, Cyp24a1 is induced by 1,25(OH)2D3 and fibroblast growth factor 23 (FGF23) and potently suppressed by PTH to control the circulating levels of 1,25(OH)2D3. Cyp24a1 is controlled by a pair of promoter proximal (PRO) vitamin D response elements (VDREs) that are aided by distal, downstream (DS) enhancers.

Design of fully synthetic signal peptide library and its use for enhanced secretory production of recombinant proteins in Corynebacterium glutamicum.

Background: Corynebacterium glutamicum is an attractive host for secretory production of recombinant proteins, including high-value industrial enzymes and therapeutic proteins. The choice of an appropriate signaling peptide is crucial for efficient protein secretion. However, due to the limited availability of signal peptides in C.

contribution of promoter vitamin D response elements.

CYP24A1 is a multifunctional, P450 mitochondrial 24-hydroxylase enzyme that is responsible for catabolism of the most active vitamin D hormone (calcitriol, 1,25(OH)D), its precursor (calcifediol, 25(OH)D), and numerous other vitamin D metabolites at the 23- and 24-carbon positions. In the kidney, is induced by 1,25(OH)D, induced by FGF23, and potently suppressed by PTH to tightly control the circulating blood levels of 1,25(OH)D. This gene is believed to be under the control of a pair of classic promoter proximal (PRO) vitamin D response elements (VDREs) that are aided by distal, downstream (DS) containing enhancers that we identified more recently.

Spatial detection and consequences of nonrenal calcitriol production as assessed by targeted mass spectrometry imaging.

The immune benefits of vitamin D3 supplementation beyond calcium and phosphate maintenance are highly clinically debated. Kidney expression of CYP27B1 is the source of endocrine, circulating 1,25(OH)2D3 (active form of vitamin D) that maintains serum calcium and phosphate. 1,25(OH)2D3 may also be made by the CYP27B1 enzyme in nonrenal cells, like immune cells, in a process driven by cellular availability of 25(OH)D3 and inflammation.

Molecular insights into mineralotropic hormone inter-regulation.

The regulation of mineral homeostasis involves the three mineralotropic hormones PTH, FGF23 and 1,25-dihydroxyvitamin D (1,25(OH)D). Early research efforts focused on PTH and 1,25(OH)D and more recently on FGF23 have revealed that each of these hormones regulates the expression of the other two. Despite early suggestions of transcriptional processes, it has been only recently that research effort have begun to delineate the genomic mechanisms underpinning this regulation for 1,25(OH)D and FGF23; the regulation of PTH by 1,25(OH)D, however, remains obscure.

Genome-wide analyses of gene expression profile identify key genes and pathways involved in skeletal response to phosphate and 1,25-dihydroxyvitamin D in vivo.

Phosphate (P) is an essential element involved in various biological actions, such as bone integrity, energy production, cell signaling and molecular component. P homeostasis is modulated by 4 main tissues; intestine, kidney, bone, and parathyroid gland, where 1,25-dihydroxyvitamin D (1,25(OH)D), parathyroid hormone and fibroblast growth factor 23 (FGF23) are produced and/or have an influence. In bone, serum P level modulates the production of FGF23 which then controls not only P excretion but also vitamin D metabolism in kidney in an endocrine manner.

Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells.

Objective: Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus.

Methods: Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase β (CaMKKβ) using immunoblotting and CPT1 enzymatic activity measures.

A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis.

The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms that control PTH-dependent vitamin D activation remain unknown. Here, we demonstrated that salt-inducible kinases (SIKs) orchestrated renal 1,25-vitamin D production downstream of PTH signaling. PTH inhibited SIK cellular activity by cAMP-dependent PKA phosphorylation.

Highlights from the 24th workshop on vitamin D in Austin, September 2022.

The 24th Workshop on Vitamin D was held September 7-9, 2022 in Austin, Texas and covered a wide diversity of research in the vitamin D field from across the globe. Here, we summarize the meeting, individual sessions, awards and presentations given.

Rapid genomic changes by mineralotropic hormones and kinase SIK inhibition drive coordinated renal Cyp27b1 and Cyp24a1 expression via CREB modules.

Vitamin D metabolism centers on kidney regulation of Cyp27b1 by mineralotropic hormones, including induction by parathyroid hormone (PTH), suppression by fibroblast growth factor 23 (FGF23) and 1,25-dihydroxyvitamin D (1,25(OH)D), and reciprocal regulations for Cyp24a1. This coordinated genomic regulation results in production of endocrine 1,25(OH)D, which, together with PTH and FGF23, controls mineral homeostasis. However, how these events are coordinated is unclear.

Genomic Mechanisms Governing Mineral Homeostasis and the Regulation and Maintenance of Vitamin D Metabolism.

Our recent genomic studies identified a complex kidney-specific enhancer module located within the introns of adjacent (M1) and (M21) genes that mediate basal and PTH induction of , as well as suppression by FGF23 and 1,25-dihydroxyvitamin D [1,25(OH)D]. The tissue specificity for this regulatory module appears to be localized exclusively to renal proximal tubules. Gross deletion of these segments in mice has severe consequences on skeletal health, and directly affects expression in the kidney.

Dibutyl phthalate exposure during gestation and lactation in C57BL/6 mice: Maternal behavior and neurodevelopment in pups.

Objectives: Neurotoxic effects of phthalate during pregnancy on immature brain of the offspring or mature brains of the mothers remain unclear. We examined the effect of dibutyl phthalate (DBP) exposure during gestation and lactation on the maternal behavior of mother mice and neurodevelopment in pups.

Methods: Pregnant mice were treated orally with DBP (0, 50 and 100 mg/kg/day, N = 20 per group) from gestational day 13 to postnatal day (PND) 15.

Rapid securing of reference substances from Peucedanum japonicum Thunberg by recycling preparative high-performance liquid chromatography.

Among the most critical needs of natural product chemistry is a complete library of pure reference substances. Some khellactone-type isomers of pharmacological importance are either still lacking reference substances or references are only available in limited amounts. To address this need, a recycling high-performance liquid chromatography (R-HPLC) strategy was adopted to improve the isomer separation efficiency from Peucedanum japonicum.

A Control Region Near the Fibroblast Growth Factor 23 Gene Mediates Response to Phosphate, 1,25(OH)2D3, and LPS In Vivo.

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone involved in the control of phosphate (P) homeostasis and vitamin D metabolism. Despite advances, however, molecular details of this gene's regulation remain uncertain. In this report, we created mouse strains in which four epigenetically marked FGF23 regulatory regions were individually deleted from the mouse genome using CRISPR/Cas9 gene-editing technology, and the consequences of these mutations were then assessed on Fgf23 expression and regulation in vivo.

A chromatin-based mechanism controls differential regulation of the cytochrome P450 gene in renal and non-renal tissues.

Cytochrome P450 family 27 subfamily B member 1 (CYP27B1) and CYP24A1 function to maintain physiological levels of 1,25-dihydroxyvitamin D (1,25(OH)D) in the kidney. Renal and expression levels are transcriptionally regulated in a highly reciprocal manner by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and 1,25(OH)D In contrast, regulation in nonrenal target cells (NRTCs) is limited to induction by 1,25(OH)D Herein, we used ChIP-Seq analyses of mouse tissues to identify regulatory regions within the gene locus. We found an extended region downstream of containing a cluster of sites, termed C24-DS1, binding PTH-sensitive cAMP-responsive element-binding protein (CREB) and a cluster termed C24-DS2 binding the vitamin D receptor (VDR).

Restoration of Cdk5, TrkB and Soluble N-ethylmaleimide-Sensitive Factor Attachment Protein Receptor Proteins after Chronic Methylphenidate Treatment in Spontaneous Hypertensive Rats, a Model for Attention-Deficit Hyperactivity Disorder.

Objective: Synaptic vesicle mobilization and neurite outgrowth regulation molecules were examined in modulation of effects of methylphenidate (MPH) in Spontaneous Hypertensive Rats (SHRs), a model for attention-deficit hyperactivity disorder (ADHD).

Methods: We compared the changes in the protein expression level of Cyclin dependent kinase 5 (Cdk5) and molecular substrates of Cdk5; tropomyosin receptor kinase B (TrkB), syntaxin 1A (STX1A) and synaptosomal-associated protein 25 (SNAP25). Comparisons were made in prefrontal cortex of vehicle (distilled water i.

Targeted genomic deletions identify diverse enhancer functions and generate a kidney-specific, endocrine-deficient pseudo-null mouse.

Vitamin D is terminally bioactivated in the kidney to 1α,25-dihydroxyvitamin D (1,25(OH)D) via cytochrome P450 family 27 subfamily B member 1 (CYP27B1), whose gene is regulated by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and 1,25(OH)D Our recent genomic studies in the mouse have revealed a complex kidney-specific enhancer module within the introns of adjacent methyltransferase-like 1 () and that mediate basal and PTH-induced expression of and FGF23- and 1,25(OH)D-mediated repression. Gross deletion of these segments in mice has severe effects on regulation and skeletal phenotype but does not affect expression in nonrenal target cells (NRTCs). Here, we report a bimodal activity in the intronic enhancer with components responsible for PTH-mediated induction and 1,25(OH)D-mediated repression and additional activities, including FGF23 repression, within the enhancers.

Fabrication Process of Bilayer RGO/PEDOT:PSS Film for Flexible Transparent Conductive Electrode.

We developed a facile method to achieve a homogeneous coating of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) on a graphene oxide (GO) layer with outstanding sheet resistance. We fabricated a transparent bilayer GO/PEDOT:PSS film as a flexible transparent conductive electrode (TCF). GO layer was coated on flexible PET and PI substrate by dip coating.

Flavin-Based Light-Driven Fluorescent Probe for the Detection of Antioxidant Amino Acids.

We have synthesized a flavin-(5)-oxide derivative with a -toluenesulfonyl () group as a "turn-on" fluorescent probe for the detection of several antioxidant amino acids and biothiols. Oxidized flavin was synthesized by using dithiothreitol as the reducing agent. showed a light-driven fluorescence enhancement in the presence of several amino acids and biothiols such as histidine (His), methionine (Met), cysteine (Cys), glutathione (GSH), and homocysteine (Hcy).