Adrenergic β receptor activation may ameliorate amyloid β toxicity. We examined whether isoproterenol, an adrenergic β receptor agonist reduces neurodegeneration caused by Aβ
1-42
, for which ...intracellular Zn
2+
dysregulation is a trigger
.
Neurodegeneration was assessed in the dentate granule cell layer 14 days after intracerebroventricular injection of human Aβ
1-42
into the mouse brain. Neurodegeneration was canceled after co-injection of isoproterenol. Isoproterenol did not affect Aβ staining (uptake) in the dentate granule cell layer 1 h after Aβ injection. In contrast, isoproterenol reduced intracellular Zn
2+
level increased by Aβ. The synthesis of intracellular metallothioneins (MTs), Zn
2+
-binding proteins was not enhanced in the dentate granule cell layer 24 h after Aβ
1-42
injection, but significantly enhanced after co-injection of isoproterenol. These data indicate that isoproterenol enhances MT synthesis and cancels neurodegeneration via intracellular Zn
2+
toxicity after Aβ
1-42
injection. It is likely that MT synthesis enhanced by adrenergic β receptor-mediated signaling contributes to ameliorating Aβ
1-42
toxicity in the brain.
•CXCL17 reduced type I collagen expression via MMP1 and miR-29 in skin fibroblasts.•CXCL17 levels in SSc skin were lower than those in healthy controls.•CXCL17 attenuated the skin fibrosis induced by ...bleomycin in mice.
Systemic sclerosis (SSc) is characterized by excessive deposition of collagen in the skin and internal organs. Recent studies have shown that chemokine (C-X-C motif) ligands (CXCLs) are involved in the pathogenesis of SSc.
Our aim was to examine the anti-fibrotic potential of CXCL17, a newly discovered chemokine, in cultured skin fibroblasts and in a bleomycin-induced SSc mouse model. Moreover, we examined serum level of CXCL17 in patients with SSc.
Type I collagen expression was evaluated in SSc skin and cultured fibroblasts treated with CXCL17 using immunoblotting and quantitative reverse transcription-PCR. Serum CXCL17 levels were determined using enzyme-linked immunosorbent assay in 63 patients with SSc and 17 healthy subjects. A bleomycin-induced SSc mouse model was used to evaluate the effect of CXCL17 on skin fibrosis.
CXCL17 reduced the expression of type I collagen in healthy control fibroblasts. CXCL17 also induced matrix metalloproteinase 1 (MMP1) and miR-29 expression in fibroblasts, indicating that CXCL17 regulates type I collagen expression in part via post-transcriptional mechanisms through MMP1 and miR-29. We found that local injection of CXCL17 attenuated bleomycin-induced skin fibrosis in mice. CXCL17 levels in SSc skin were lower than those in healthy controls, in contrast to the high serum CXCL17 levels in patients with SSc. The low expression of CXCL17 in SSc skin possibly affects type I collagen accumulation in this disease.
Our data indicate that understanding CXCL17 signaling may lead to a better therapeutic approach for SSc.
The photophysics and photostability of 9,10-bis(phenylethynyl)anthracene (BPEA) diluted in a 40-nm-thick Zeonex polymer film have been investigated by single-molecule spectroscopy (SMS). The ...single-molecule detection of BPEA was verified by recording fluorescence intensity trajectories, fluorescence lifetimes, and fluorescence spectra. The intensity trajectories showed frequent on/off blinking and one-step photobleaching behaviors. The observed blinking was attributed to the temporary occupation of the excited triplet state T sub(1) via intersystem crossing (ISC). Assuming a three-state model (e.g., S sub(0), S sub(1), and T sub(1)), the distributions of triplet lifetime and S sub(1) arrow right T sub(1) ISC quantum yield of BPEA were both derived from the analyses of the blinking statistics and the intensity autocorrelation. We found extremely low ISC yields (on the order of 10 super(-5)-10 super(-4)), which were theoretically rationalized by the large energy gap between super(3)B sub(2u) and S sub(1)( super(1)B sub(1 u))/T sub(1)( super(3)B sub(1u)) states. SMS measurements were also conducted under both air and Ar atmospheres in order to gain insight into the influence of oxygen on photobleaching. The results reveal that, although the presence of oxygen considerably degraded the photostability of BPEA, under deoxygenated conditions, BPEA delivers more than 10 super(7) photons before photobleaching and possesses an appreciably low photobleaching yield of 10 super(-9)-10 super(-8). This study shows that BPEA has a relatively high degree of photostability at room temperature and can serve as a useful green fluorescent probe for SMS studies.
Although royal jelly is believed to prevent skin aging, the underlying mechanism is not known in detail. In the present study, we investigated the plausibility of the involvement of microRNAs in the ...manifestation of this effect of royal jelly. The expression of microRNAs was determined by PCR array analysis and real-time PCR and the number of cells was counted with a cell counter. Using PCR array, we identified four microRNAs that were downregulated by royal jelly in cultured human dermal microvascular endothelial cells (HDMEC). Upon comparison of the expression of the four microRNAs between young and senescent facial skin, miR-129-5p was found to be significantly upregulated in senescent skin. Consistently, the expression of miR-129-5p in HDMEC was significantly increased by UVB radiation, suggesting that this microRNA is related to photoaging. The royal jelly treatment increased the number of HDMEC. Furthermore, forced overexpression of miR-129-5p resulted in significant decrease in the number of HDMEC, and its forced downregulation increased the number of cells. The number and density of vessels is reported to be decreased in aged skin. Our results indicate that miR-129-5p is induced in damaged endothelial cells upon exposure to UV radiation, which decreases the cell number. Furthermore, administration of royal jelly downregulated the expression of miR-129-5p in endothelial cells, and might prevent skin aging by maintaining the number of cells. The present study elucidates the mechanism of vessel aging caused by UV exposure and the anti-aging effects of royal jelly through the involvement of microRNA.
Muscle satellite cells (MuSCs), myogenic stem cells in skeletal muscles, play an essential role in muscle regeneration. After skeletal muscle injury, quiescent MuSCs are activated to enter the cell ...cycle and proliferate, thereby initiating regeneration; however, the mechanisms that ensure successful MuSC division, including chromosome segregation, remain unclear. Here, we show that PIEZO1, a calcium ion (Ca
)-permeable cation channel activated by membrane tension, mediates spontaneous Ca
influx to control the regenerative function of MuSCs. Our genetic engineering approach in mice revealed that PIEZO1 is functionally expressed in MuSCs and that
deletion in these cells delays myofibre regeneration after injury. These results are, at least in part, due to a mitotic defect in MuSCs. Mechanistically, this phenotype is caused by impaired PIEZO1-Rho signalling during myogenesis. Thus, we provide the first concrete evidence that PIEZO1, a bona fide mechanosensitive ion channel, promotes proliferation and regenerative functions of MuSCs through precise control of cell division.
A Raman lidar with a deep ultraviolet laser was constructed to continuously monitor water vapor distributions in the atmospheric boundary layer for twenty-four hours. We employ a laser at a ...wavelength of 266 nm and detects the light separated into an elastic backscatter signal and vibrational Raman signals of oxygen, nitrogen, and water vapor. The lidar was encased in a temperature-controlled and vibration-isolated compact container, resistant to a variety of environmental conditions. Water vapor profile observations were made for twelve months from November 24, 2017, to November 29, 2018. These observations were compared with collocated radiosonde measurements for daytime and nighttime conditions.
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► Tc/pTP-NPs at various doping ratios are produced by reprecipitation in water. ► The energy transfer in Tc/pTP-NPs is investigated. ► More than 104pTP donors were quenched by a ...single Tc acceptor. ► Efficient energy transfer is attributed to the rapid exciton diffusion in the NPs.
A series of tetracene (Tc)-doped p-terphenyl (pTP) nanoparticles (Tc/pTP-NPs) were produced at various doping ratios by reprecipitation in water. The Tc/pTP-NPs are disk-like with a mean diameter of 75nm and height of 7nm, which were determined by scanning electron microscopy and atomic force microscopy, and exhibited electronic delocalization through H-type aggregation of the pTP molecules. Electronic energy transfer in the Tc/pTP-NPs was examined using steady-state and time-resolved fluorescence spectroscopy and fluorescence anisotropy experiments: pTP-NPs serve as an excellent light-harvesting nano-matrix with a large absorption coefficient that exceeds 109M−1cm−1. Furthermore, Stern–Volmer analysis of the donor emission was performed by changing the dopant concentration; this showed that a single Tc acceptor quenched more than 104pTP donors. Comparison of the experimental and theoretical energy transfer efficiencies indicated that the efficient energy transfer can be attributed to two-dimensional exciton diffusion in the host nanoparticles.
Adrenergic β receptor activation may ameliorate amyloid β toxicity. We examined whether isoproterenol, an adrenergic β receptor agonist reduces neurodegeneration caused by Aβ
, for which ...intracellular Zn
dysregulation is a trigger. Neurodegeneration was assessed in the dentate granule cell layer 14 days after intracerebroventricular injection of human Aβ
into the mouse brain. Neurodegeneration was canceled after co-injection of isoproterenol. Isoproterenol did not affect Aβ staining (uptake) in the dentate granule cell layer 1 h after Aβ injection. In contrast, isoproterenol reduced intracellular Zn
level increased by Aβ. The synthesis of intracellular metallothioneins (MTs), Zn
-binding proteins was not enhanced in the dentate granule cell layer 24 h after Aβ
injection, but significantly enhanced after co-injection of isoproterenol. These data indicate that isoproterenol enhances MT synthesis and cancels neurodegeneration via intracellular Zn
toxicity after Aβ
injection. It is likely that MT synthesis enhanced by adrenergic β receptor-mediated signaling contributes to ameliorating Aβ
toxicity in the brain.
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