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1.
Tohoku J Exp Med ; 263(4): 227-238, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-38811212

RESUMEN

Arteriosclerosis obliterans (ASO) is characterized by arterial narrowing and blockage due to atherosclerosis, influenced by endothelial dysfunction and inflammation. This research focuses on exploring the role of MAGOH-DT, a long noncoding RNA, in mediating endothelial cell dysfunction through endothelial-mesenchymal transition (EndMT) under inflammatory and hyperglycemic stimuli, aiming to uncover potential therapeutic targets for ASO. Differential expression of lncRNAs, including MAGOH-DT, was initially identified in arterial tissues from ASO patients compared to healthy controls through lncRNA microarray analysis. Validation of MAGOH-DT expression in response to tumor necrosis factor-alpha (TNF-α) and high glucose (HG) was performed in human umbilical vein endothelial cells (HUVECs) using RT-qPCR. The effects of MAGOH-DT and HNRPC knockdown on EndMT were assessed by evaluating EndMT markers and TGF-ß2 protein expression with Western blot analysis. RNA-immunoprecipitation assays were used to explore the interaction between MAGOH-DT and HNRPC, focusing on their role in regulating TGF-ß2 translation. In the results, MAGOH-DT expression is found to be upregulated in ASO and further induced in HUVECs under TNF-α/HG conditions, contributing to the facilitation of EndMT. Silencing MAGOH-DT or HNRPC is shown to inhibit the TNF-α/HG-induced increase in TGF-ß2 protein expression, effectively attenuating EndMT processes without altering TGF-ß2 mRNA levels. In conclusion, MAGOH-DT is identified as a key mediator in the process of TNF-α/HG-induced EndMT in ASO, offering a promising therapeutic target. Inhibition of MAGOH-DT presents a novel therapeutic strategy for ASO management, especially in cases complicated by diabetes mellitus. Further exploration into the therapeutic implications of MAGOH-DT modulation in ASO treatment is warranted.


Asunto(s)
Arteriosclerosis Obliterante , Transición Epitelial-Mesenquimal , Glucosa , Células Endoteliales de la Vena Umbilical Humana , ARN Largo no Codificante , Factor de Necrosis Tumoral alfa , Regulación hacia Arriba , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética , Arteriosclerosis Obliterante/genética , Arteriosclerosis Obliterante/metabolismo , Arteriosclerosis Obliterante/patología , Glucosa/farmacología , Transición Epitelial-Mesenquimal/genética , Transición Epitelial-Mesenquimal/efectos de los fármacos , Factor de Crecimiento Transformador beta2/metabolismo , Factor de Crecimiento Transformador beta2/genética , Masculino , Transición Endotelial-Mesenquimatosa
2.
Inorg Chem ; 62(37): 14863-14872, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37676750

RESUMEN

Cooperative spin crossover transitions with thermal hysteresis loops are rarely observed in cobalt(II) complexes. Herein, two new mononuclear cobalt(II) complexes with hysteretic spin crossover at relatively high temperatures (from 320 to 400 K), namely, [Co(terpy-CH2OH)2]·X2 (terpy-CH2OH = 4'-(hydroxymethyl)-2,2';6',2″-terpyridine, X = SCN-(1) and SeCN- (2)), have been synthesized and characterized structurally and magnetically. Both compounds are mononuclear CoII complexes with two chelating terpy-CH2OH ligands. Magnetic measurements revealed the existence of the hysteretic SCO transitions for both complexes. For compound 1, a one-step transition with T1/2↑= 334.5 K was observed upon heating, while a two-step transition is observed upon cooling with T1/2↓(1) = 329.3 K and T1/2↓(2) = 324.1 K (at a temperature sweep rate of 5 K/min). As for compound 2, a hysteresis loop with a width of 5 K (T1/2↓ = 391.6 K and T1/2↑ = 396.6 K, at a sweep rate of 5 K/min) can be observed. Thanks to the absence of the crystallized lattice solvents, their single crystals are stable enough at high temperatures for the structure determination at both spin states, which reveals that the hysteretic SCO transitions in both complexes originate from the crystallographic phase transitions involving a thermally induced order-disorder transition of the dangling -CH2OH groups in the ligand. This work shows that the modification of the terpy ligand has an important effect on the magnetic properties of the resulting cobalt(II) complexes.

3.
Dalton Trans ; 48(24): 8843-8852, 2019 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-31139790

RESUMEN

The rational design and synthesis of heptacyanomolybdate-based magnets remain a challenge due to the complexity of this system. Here, we reported the crystal structures and magnetic properties of two three-dimensional (3D) frameworks prepared from the self-assembly of the [MoIII(CN)7]4- unit with MnII ions in the presence of different amide ligands, namely Mn2(DMF)(H2O)2[Mo(CN)7]·H2O·CH3OH (1) and Mn2(DEF)(H2O)[Mo(CN)7] (2) (DMF = N,N'-dimethylformamide and DEF = N,N'-diethylformamide). Single-crystal structure determinations showed that compound 1 crystallizes in the triclinic space group Pi, while 2 crystallizes in the monoclinic space group P21/n. The difference in the structures of 1 and 2 is the coordination mode of the amide molecules: while the DMF molecules in 1 are only terminal ligands, the DEF molecules in 2 act as bridging ligands between two MnII centers. Although their space groups and local coordination environments of the metal centers are of some difference, both compounds have similar extended 3D frameworks where the spin centers are bridged by both the CN- and µ2-O bridges. They both have a three-nodal 4, 4, 7-connecting topological net with the vertex symbol of {43·53}{44·52}{47·54·66·74} for 1, and {43·53}{44·52}{47·54·67·73} for 2, respectively. Magnetic measurements revealed that both 1 and 2 exhibit ferrimagnetic ordering below 80 K together with another anomaly at about 45 K probably owing to spin reorientation. Besides, spin frustration and non-linear alignment of the magnetic moments are also possible due to competitive antiferromagnetic interactions between the spin carriers. These compounds expanded the family of MnII-[MoIII(CN)7]4- magnets with high magnetic ordering temperatures.

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