The construction of type-II van der Waals heterostructure is an effective method to design efficient photocatalysts. In this study, we constructed PtSe/SiH van der Waals heterojunction, investigated its structural, electronic...
We investigated the role of HIF-1α in the mitigation of cisplatin-induced nephrotoxicity by Panax notoginseng saponins (PNS) in a rat model. Serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-β-D-glucosaminidase (NAG) levels were all elevated in cisplatin treated rats. PNS reduced Scr, BUN and NAG levels in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2ME2). PNS also reduced the high tubular injury scores, which corresponded to renal tubular damage in cisplatin-treated rats and which were exacerbated by 2ME2. Renal tissues from PNS-treated rats showed increased HIF-1α mRNA and nuclear localized HIF-1α protein. Moreover, PNS treatment increased BNIP3 mRNA as well as LC3-II, BNIP3 and Beclin-1 proteins and the LC3-II/LC3-I ratio in rat renal tissues. This suggested that PNS treatment enhanced HIF-1α, which in turn increased autophagy. This was confirmed in transmission electron micrographs of renal tissues that showed autophagosomes in PNS-treated renal tissues. These findings demonstrate that PNS mitigates cisplatin-induced nephrotoxicity by enhancing mitophagy via a HIF-1α/BNIP3/Beclin-1 signaling pathway.
Molecular organization of a cell is dynamically transformed along the course of cellular physiological processes, pathologic developments or derived from interactions with drugs. The capability to measure and monitor concentrations of macromolecules in a single cell would greatly enhance studies of cellular processes in heterogeneous populations. In this communication, we introduce and experimentally validate a bio-analytical single-cell assay, wherein the overall concentration of macromolecules is estimated in specific subcellular domains, such as structure-function compartments of the cell nucleus as well as in nucleoplasm. We describe quantitative mapping of local biomolecular concentrations, either intrinsic relating to the functional and physiological state of a cell, or altered by a therapeutic drug action, using two-photon excited fluorescence lifetime imaging (FLIM). The proposed assay utilizes a correlation between the fluorescence lifetime of fluorophore and the refractive index of its microenvironment varying due to changes in the concentrations of macromolecules, mainly proteins. Two-photon excitation in Near-Infra Red biological transparency window reduced the photo-toxicity in live cells, as compared with a conventional single-photon approach. Using this new assay, we estimated average concentrations of proteins in the compartments of nuclear speckles and in the nucleoplasm at ~150 mg/ml, and in the nucleolus at ~284 mg/ml. Furthermore, we show a profound influence of pharmaceutical inhibitors of RNA synthesis on intracellular protein density. The approach proposed here will significantly advance theranostics, and studies of drug-cell interactions at the single-cell level, aiding development of personal molecular medicine.
Raman scattering
provides stable narrow-banded signals that potentially
allow for multicolor microscopic imaging. The major obstacle for the
applications of Raman spectroscopy and microscopy is the small cross
section of Raman scattering that results in low sensitivity. Here,
we report a new concept of azo-enhanced Raman scattering (AERS) by
designing the intrinsic molecular structures using resonance Raman
and concomitant fluorescence quenching strategies. Based on the selection
of vibrational modes and the enhancing unit of azobenzenes, we obtained
a library of AERS molecules with specific Raman signals in the fingerprint
and silent frequency regions. The spectral characterization and molecular
simulation revealed that the azobenzene unit conjugated to the vibrational
modes significantly enhanced Raman signals due to the mechanism of
extending the conjugation system, coupling the electronic–vibrational
transitions, and improving the symmetry of vibrational modes. The
nonradiative decay of azobenzene from the excited state quenched the
commitment fluorescence, thus providing a clean background for identifying
Raman scattering. The most sensitive AERS molecules produced Raman
signals of more than 4 orders of magnitude compared to 5-ethynyl-2′-deoxyuridine
(EdU). In addition, a frequency tunability of 10 distinct Raman bands
was achieved by selecting different types of vibrational modes. This
methodology of AERS allows for designing small-molecule Raman probes
to visualize various entities in complex systems by multicolor spontaneous
Raman imaging. It will open new prospects to explore innovative applications
of AERS in interdisciplinary research fields.
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