Hepatic CYP3A4 Enzyme Compensatively Maintains Endogenous Geranylgeranoic Acid Levels in -Knockout Human Hepatoma Cells.

Geranylgeranoic acid (GGA), developed as a preventive agent against second primary hepatoma, has been reported to be biosynthesized via the mevalonate pathway in human hepatoma-derived cells. Recently, we found that monoamine oxidase B (MAOB) catalyzed the oxidation of geranylgeraniol (GGOH) to produce geranylgeranial (GGal), a direct precursor of endogenous GGA in hepatoma cells, using tranylcypromine, an inhibitor of MAOs, and knockdown by siRNA. However, endogenous GGA level was unexpectedly unchanged in -knockout (KO) cells established using the CRISPR-Cas9 system, suggesting that some other latent metabolic pathways maintain endogenous GGA levels in the -KO cells.

Age-Dependent Decrease in Hepatic Geranylgeranoic Acid Content in C3H/HeN Mice and Its Oral Supplementation Prevents Spontaneous Hepatoma.

Geranylgeranoic acid (GGA) has been developed as a preventive agent against second primary hepatoma. Recently, GGA was reported to induce cell death in human hepatoma cells via TLR4-mediated pyroptosis. We have reported that GGA is enzymatically biosynthesized from mevalonic acid in human hepatoma-derived cells and that endogenous GGA is found in most organs of rats.

Use of Parathyroid Hormone and Rehabilitation Reduces Subsequent Vertebral Body Fractures after Balloon Kyphoplasty.

Study Design: Retrospective cohort study.

Purpose: To evaluate the efficacy of our current prophylactic strategy by investigating the incidence of subsequent vertebral body fractures (SVBFs) following balloon kyphoplasty (BKP).

Overview Of Literature: Although extensive studies have investigated the risk factors for SVBFs after BKP, few have reported on postoperative therapies to prevent SVBFs and have evaluated their effectiveness.

Hepatic monoamine oxidase B is involved in endogenous geranylgeranoic acid synthesis in mammalian liver cells.

Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from C-mevalonate.

Engineering pH-responsive switching of donor-π-acceptor chromophore alignments along a peptide nanotube scaffold.

A cyclic tri-β-peptide cyclo(β-Ala-β-Ala-β-Lys) having diethylaminonaphthalimide at the β-Lys side chain (CP3Npi) self-assembled into a peptide nanotube in a solution of HFIP and water. CD spectra of the CP3Npi nanotubes show a negative Cotton effect at 441 nm and a positive Cotton effect at 393 nm, indicating that D-π-A naphthalimide chromophores are aligned in a left-handed chiral way along the nanotube. The CP3Npi nanotubes bear positive charges under acidic conditions retaining the nanotube structure but pH-responsive switching of D-π-A naphthalimide alignments along the nanotube between a left-handed chiral and random arrangement was observed.

Endocannabinoid Signaling from 2-Arachidonoylglycerol to CB Cannabinoid Receptor Facilitates Reward-based Learning of Motor Sequence.

The endocannabinoid system modulates synaptic transmission, controls neuronal excitability, and is involved in various brain functions including learning and memory. 2-arachidonoylglycerol, a major endocannabinoid produced by diacylglycerol lipase-α (DGLα), is released from postsynaptic neurons, retrogradely activates presynaptic CB cannabinoid receptors, and induces short-term or long-term synaptic plasticity. To examine whether and how the endocannabinoid system contributes to reward-based learning of a motor sequence, we subjected male CB-knockout (KO) and DGLα-KO mice to three types of operant lever-press tasks.

Chiral and random arrangements of flavin chromophores along cyclic peptide nanotubes on gold influencing differently on surface potential and piezoelectricity.

Two kinds of peptide nanotubes are prepared from cyclo(β-Asp(flavin)-β-alanine-β-alanine) (C3FAA) and cyclo(β-Asp(flavin)-ethylenediamine-succinic acid) (C3FES). The flavin chromophores are protruding on the C3FAA and C3FES peptide nanotube surfaces in random and chiral ways, respectively. The surface potentials of the C3FAA nanotube bundles on a gold substrate become larger than the C3FES nanotube bundles of the corresponding thicknesses.

Unequivocal evidence for endogenous geranylgeranoic acid biosynthesized from mevalonate in mammalian cells.

Geranylgeranoic acid (GGA) has been reported to induce autophagic cell death via upregulation of lipid-induced unfolded protein response in several human hepatoma-derived cell lines, and its 4,5-didehydro derivative has been developed as a preventive agent against second primary hepatoma in clinical trials. We have previously reported that GGA is a natural diterpenoid synthesized in several medicinal herbs. Here, we provide unequivocal evidence for de novo GGA biosynthesis in mammals.

Piezoelectric property of bundled peptide nanotubes stapled by bis-cyclic-β-peptide.

Cyclic tetra-β-peptides (CP4s) and a bis-CP4 were synthesized to prepare peptide nanotubes (PNTs) by molecular stacking of cyclic peptides. The addition of bis-CP4 to the PNT preparation afforded PNT bundles increasing the direct and converse piezoelectiric coefficients, which is ascribable to bis-CP4 stapling PNTs into the parallel alignment of PNT dipoles.

Two one-dimensional arrays of naphthyl and anthryl groups along peptide nanotubes prepared from cyclic peptides comprising α- and β-amino acids.

A novel cyclic hexapeptide composed of l-α-naphthylalanine, d-α-anthrylalanine, and four β-alanines (CP6) is synthesized and its molecular assembly into peptide nanotubes (PNTs) and the electronic properties arising from one-dimensional arrays of aromatic groups along the PNTs were investigated. CP6 with a combination of l- and d-α-amino acids is designed to self-assemble into PNTs with them stacking on top of each other under the constraint of maximizing the number of intermolecular hydrogen bonds between the cyclic peptides. Upon PNT formation, the respective side chains of l- and d-α-amino acids are aligned in line along the PNTs.

CD28 co-stimulation is dispensable for the steady state homeostasis of intestinal regulatory T cells.

It is well-established that CD28 co-stimulation is required for the development and the proliferation of thymus-derived regulatory T cells (tTregs). Meanwhile, the role of CD28 co-stimulation in the homeostasis of peripherally derived Tregs (pTregs) remains unclear. To clarify this issue, we analyzed Tregs in small and large intestines (SI and LI), the principle sites of pTreg development.

Peptide nanotube aligning side chains onto one side.

A novel pseudo cyclic penta-β-peptide composed of a β-naphthylalanine, two β-alanines, and a sequence of ethylenediamine-succinic acid (CP5ES) is synthesized and investigated on peptide nanotube (PNT) formation. When the PNT is formed with the maximum number of intermolecular hydrogen bonds between the cyclic peptides, the sequence enables the alignment of the side chains, naphthyl groups, on one side of the PNT. Microscopic and spectroscopic observations of CP5ES crystals reveal that CP5ES forms rod- or needle-shaped molecular assemblies showing exciton coupling of the Cotton effect and predominant monomer emission, which are different from a reference cyclic tri-β-peptide composed of a β-naphthylalanine and two β-alanines.

Genetic screening for regulators of Prz1, a transcriptional factor acting downstream of calcineurin in fission yeast.

Calcineurin phosphatase plays crucial roles in a wide variety of cell types and organisms. Dephosphorylation of the nuclear factor of activated T-cell (NFAT) family of transcriptional factors by calcineurin is essential for activating immune-responsive genes in mammals. NFAT activity is also regulated by diverse signaling pathways, which affect NFAT kinases and nuclear partner proteins.