Cisplatin (CP), which is a conventional cancer chemotherapeutic drug, induces apoptosis by modulating a diverse array of gene regulatory mechanisms. However, cisplatin-mediated changes in the m6A methylome are unknown. We employed an m6A miCLIP-seq approach to investigate the effect of m6A methylation marks under cisplatin-mediated apoptotic conditions on HeLa cells. Our high-resolution approach revealed numerous m6A marks on 972 target mRNAs with an enrichment on 132 apoptotic mRNAs. We tracked the fate of differentially methylated candidate mRNAs under METTL3 knockdown and cisplatin treatment conditions. Polysome profile analyses revealed perturbations in the translational efficiency of PMAIP1 and PHLDA1 transcripts. Congruently, PMAIP1 amounts were dependent on METTL3. Additionally, cisplatin-mediated apoptosis was sensitized by METTL3 knockdown. These results suggest that apoptotic pathways are modulated by m6A methylation events and that the METTL3–PMAIP1 axis modulates cisplatin-mediated apoptosis in HeLa cells.
Novel bis-lanthanide Lu(iii) and Eu(iii) phthalocyanine complexes have been designed/synthesized and tested their photodynamic efficacy for A549 and BEAS-2B cells in vitro conditions as candidate photosensitizers in PDT.
This letter describes formation of single chain cationic polymer dots (Pdots) made of poly [1,4-dimethyl-1-(3-((2,4,5-trimethylthiophen-3yl)oxy)propyl)piperazin-1-ium bromide] conjugated polyelectrolyte (CPE). The single chain Pdot formation relies on a simple process which is a rapid nanophase separation between CPE solution of ethylene glycol and water. Pdots show narrow monodisperse size distribution with a 3.6 nm in diameter exhibiting high brightness and excellent colloidal and optical stability. It has been demonstrated that photoluminescent Pdots provide selective nuclear translocation to hepatocellular carcinoma cells as compared to healthy liver cells. The Pdot labeling effectively discriminates cancer cells in the coculture media. Pdots hold great promise as a luminescent probe to diagnose cancer cells in histology and may guide surgeons during operations to precisely separate out cancerous tissue due to augmented fluorescence brightness.
There are a number of lipophilic cations that can be
chosen; the
triphenylphosphonium (TPP) ion is particularly unique for mitochondrion
targeting, mainly due to its simplicity in structure and ease to be
linked to the target molecules. In this work, mitochondrion-targeted
AB3-type novel phthalocyanine and porphyrin photosensitizers
(PSs) were synthesized and their photophysical photochemical properties
were defined. Fluorescence quantum yields (ΦF) are
0.009, 0.14, 0.13, and 0.13, and the singlet-oxygen quantum yields
(ΦΔ) are 0.27, 0.75, 0.57, and 0.58 for LuPcPox(OAc), AB
3
TPP-Pc, AB
3
TPP-Por-C4, and AB
3
TPP-Por-C6, respectively. To evaluate the photodynamic efficacy of the TPP-conjugated
PS cell viabilities of A549 and BEAS-2B lung cells were comparatively
measured and IC-50 values were determined. AB
3
TPP-Por-C4, AB
3
TPP-Por-C6, and AB
3
TPP-Pc compounds compared to the reference
molecules ZnPc and H
2
TPP were found to be highly cytotoxic (sub-micromolar
concentration) under the light. LuPcPox(OAc) is the most
effective molecule regarding cell killing (the activity). The cell
killing of the TPP-conjugated porphyrin derivatives exhibits a similar
response compared to LuPcPox(OAc) when the light absorbing
factor of the PS is normalized at 660 nm: TPP-conjugated porphyrins
absorb less light (lower extinction coefficient) but produce more
radical species (higher singlet-oxygen quantum yield) and therefore
effectively kill the cells. The singlet oxygen-producing capacity
of AB
3
TPP-Pc is
almost 3 times higher compared to LuPcPox(OAc) and 50%
more efficient with respect to ZnPc, suggesting that TPP-conjugated
phthalocyanine may serve as a good photosensitizer for photodynamic
therapy (PDT). The high singlet oxygen generation capacity of these
novel TPP-conjugated porphyrin and phthalocyanine PS suggests that
they might be useful for PDT requiring lower photosensitizer concentration
and reduced energy deposited through less light exposure.
JT03292158Turkey has considerably improved its terms of access to the global capital market. Progress in macroeconomic fundamentals has enhanced credibility and reduced risk premia and capital costs. This has had broad effects on capital supply conditions in the entire economy. Real interest rates have declined, and funds of lengthened maturity are becoming available for a broader range of borrowers and fund users, offering a basis for broader-based long-term growth. Estimations in the paper suggest that reinforcing fiscal institutions, price stability, governance quality, political stability and trade and growth performance would help Turkey to continue to improve its integration with the international capital market and reduce durably its capital costs. This paper relates to the 2010 OECD Economic Review of Turkey (www.oecd.org/eco/surveys/turkey).JEL classification: E43 ; E44 ; E62 ; F34 ; F43 ; G15 Keywords: Open economy; capital markets; risk premia; interest rates; capital costs; fiscal institutions; credit rating; economic growth **********************
L'Intégration Croissante de la Turquie avec le Marché Global des Capitaux : Effets sur Les Primes de Risque et Cout du CapitalLa Turquie a considérablement amélioré ses conditions d'accès au marché global des capitaux. Des progrès dans les fondamentaux macroéconomiques ont renforcé la crédibilité et réduit les primes de risque et le coût du capital. Cela a eu des conséquences considérables sur les conditions de financement de l'économie tout entière. Les taux d'intérêt réels ont diminué, et des fonds à plus longue maturité deviennent disponibles pour un plus large éventail d'utilisateurs de fonds, offrant une base plus large pour la croissance à long terme. Les estimations dans le document suggèrent que le renforcement des institutions budgétaires, de la stabilité des prix, de la qualité de la gouvernance, de la stabilité politique et de la performance du commerce extérieur et de la croissance aiderait la Turquie à continuer à améliorer son intégration avec le marché global des capitaux et à réduire durablement ses coûts en capital. Ce document se rapporte à l'Étude économique de Turquie de l'OCDE, 2010, (www.oecd.org/eco/surveys/turkey).
Cisplatin, which is a traditional cancer therapeutic drug, induces apoptosis by modulating a diverse array of gene regulatory mechanisms. However, cisplatin-mediated changes in the m6A methylome is unknown. We employed m6A miCLIP-seq to investigate the effect of m6A methylation events under cisplatin-mediated apoptotic conditions in HeLa cells. Our high-resolution approach revealed numerous m6A marks on 972 target mRNAs with an enrichment on 132 apoptotic mRNAs. Following validation of site-specific m6A events on candidate RNAs, we tracked the fate of candidate mRNAs under METTL3 knockdown and cisplatin treatment conditions. We detected perturbations in the translational efficiency of PMAIP1 and PHLDA1 transcripts based on the polysome profile analyses. Congruently, PMAIP1 and p53 amounts were dependent on METTL3. Additionally, cisplatin-mediated apoptosis was sensitized by METTL3 knockdown. These results suggest that apoptotic pathways are modulated by m6A methylation events and METTL3-p53-PMAIP1 axis modulates cisplatin-mediated apoptosis in HeLa cells.
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