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1.
Zool Res ; 45(2): 355-366, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38485505

RESUMO

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood, especially in teleosts. In this study, cyp17a1-/- zebrafish ( Danio rerio) exhibited excessive visceral adipose tissue (VAT), lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis (DNL) enzymes. The assay for transposase accessible chromatin with sequencing (ATAC-seq) results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/- fish compared to cyp17a1+/+ male fish, including stearoyl-CoA desaturase ( scd) and fatty acid synthase ( fasn). Androgen response element (ARE) motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+ male fish but not in cyp17a1-/- fish. Both androgen receptor ( ar)-/- and wild-type (WT) zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue, lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis enzymes. The Ar agonist BMS-564929 reduced the content of VAT and lipid content, and down-regulated acetyl-CoA carboxylase a ( acaca), fasn, and scd expression. Mechanistically, the rescue effect of testosterone on cyp17a1-/- fish in terms of phenotypes was abolished when ar was additionally depleted. Collectively, these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish, thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.


Assuntos
Androgênios , Lipogênese , Masculino , Animais , Androgênios/farmacologia , Lipogênese/genética , Peixe-Zebra/genética , Testosterona , Lipídeos , Transdução de Sinais , Cromatina
2.
J Phys Chem B ; 127(38): 8116-8130, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37725055

RESUMO

Recycling Kr and Xe from used nuclear fuel (UNF) is conducive to regenerating economy and protecting the environment, and it is urgent to screen or design high-performance cutting-edge metal-organic framework (MOF) materials for Kr/Xe adsorption separation. After grand canonical Monte Carlo (GCMC) simulations of Kr/Xe adsorption separation on 11,000 frameworks in CoRE MOFs (2019), the important structure-adsorption property relationship (SAPR) was induced; that is, the porosity (φ) at 0.30-0.40, LCD/PLD at 1.00-1.49, density (ρ) range between 1.20 and 2.30 g/cm3, and PLD at 2.40-3.38 Å can be utilized to screen for high-performance G-MOFs and hMOFs. In addition, the key "genes" (metal nodes and linkers) of MOFs determining the Kr/Xe adsorption separation were data-mined by a machine learning technique, which were assembled into novel MOFs. After comprehensive consideration of thermal stability and the adsorbent performance score (APS), eight promising MOFs on Kr/Xe separation with the APS more than 1290.89 were screened out and assembled, which are better than most of the reported frameworks. Note that the adsorption isotherms of these MOFs on Kr and Xe belong to type I curve with the thermodynamic equilibrium mechanism on Kr/Xe based on the confinement effect. Furthermore, according to the electronic structure calculations of the independent gradient model based on Hirshfeld partition (IGMH) and energy decomposition analysis, it is found that the interactions between guests and frameworks are vdW forces with dominant induction energy (Eind). In addition, the electrostatic potential gradients of frameworks are generally linearly negative correlated with Kr uptakes. Therefore, both the geometrical and electronic structures dominate the adsorption separation performance on Kr/Xe. Interestingly, these eight MOFs are also suitable for the separation of CH4/H2 with considerable selectivities and CH4 uptakes of up to 2566.67 and 3.04 mmol/g, respectively. Herein, the accurately constructed SAPR and material genomics strategy should be helpful for the experimental discovery of novel MOFs on Kr/Xe separation experimentally.

3.
Dalton Trans ; 52(33): 11451-11457, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37547997

RESUMO

Heterometallic oxo clusters have been attracting intensive interest due to their unique properties originating from the synergistic interactions between different components. Herein, we report the construction and catalytic applications of a family of copper-doped polyoxo-titanium clusters (Cu-PTCs) coordinated with different acetate derivative ligands. The solvothermal reactions of metal salts and trimethylacetic acid or 1,2-phenylenediacetic acid in ethanol produced Ti6Cu3(µ3-O)4(µ2-O)(OEt)16(L1)4 (L1 = trimethyl acetate, PTC-367) and H2Ti8Cu2Br2(µ4-O)2(µ2-O)4(OEt)20(L2)2 (L2 = 1,2-phenylenediacetate, PTC-368), respectively. When smaller acetic acid was introduced as a stabilizing ligand, higher nuclei H2Ti16Cu3(µ4-O)5(µ3-O)15(µ2-O)3(OiPr)18(Ac)8 (Ac = acetate, PTC-369) and H3Ti29Cu3(µ4-O)6(µ3-O)30(µ2-O)8(OiPr)17(Ac)20 (PTC-370) were prepared. The number of metal ions exposed on the surface of the four clusters changes due to variations in the steric hindrance of functionalizing ligands, and theoretically, so does their catalytic activity as Lewis acids. In light of this, we conducted a carbon dioxide cycloaddition reaction in an atmospheric environment and the four obtained compounds displayed increasing catalytic activities from PTC-367 to PTC-370. These results provide a feasible synthetic method for modulating the structures of Cu-doped titanium oxide materials and improving their catalytic activities.

4.
Molecules ; 28(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36903547

RESUMO

Herein, the combination of anionic Zr4L6 (L = embonate) cages and N, N-chelated transition-metal cations leads to a series of new cage-based architectures, including ion pair structures (PTC-355 and PTC-356), dimer (PTC-357), and 3D frameworks (PTC-358 and PTC-359). Structural analyses show that PTC-358 exhibits a 2-fold interpenetrating framework with a 3,4-connected topology, and PTC-359 shows a 2-fold interpenetrating framework with a 4-connected dia network. Both PTC-358 and PTC-359 can be stable in air and other common solvents at room temperature. The investigations of third-order nonlinear optical (NLO) properties indicate that these materials show different degrees of optical limiting effects. It is surprising that increasing coordination interactions between anion and cation moieties can effectively enhance their third-order NLO properties, which can be attributed to the formation of coordination bonds that facilitate charge transfer. In addition, the phase purity, UV-vis spectra, and photocurrent properties of these materials were also studied. This work provides new ideas for the construction of third-order NLO materials.

5.
Dalton Trans ; 52(7): 1857-1860, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36723102

RESUMO

Herein, we report a twisted cubic Cu(I)4Ti(IV)4-oxo cluster stabilized by in situ - formed 2,2'-biphenolate ligands from the oxidative coupling of phenols. The 2,2'-biphenolate-functionalized Cu(I)4Ti(IV)4O4 cluster shows short Cu⋯C contacts and exhibits smaller HOMO-LUMO gaps than those of reported Ti(IV)4O4.

6.
Angew Chem Int Ed Engl ; 62(16): e202300726, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-36807676

RESUMO

A chiral metal-organic cage (MOC) was extended and fixed into a porous framework using a post-assembly modification strategy, which made it easier to study the host-guest chemistry of the solid-state MOC using a single-crystal diffraction technique. Anionic Ti4 L6 (L=embonate) cage can be used as a 4-connecting crystal engineering tecton, and its optical resolution was achieved, thus homochiral ΔΔΔΔ- and ΛΛΛΛ-[Ti4 L6 ] cages were obtained. Accordingly, a pair of homochiral cage-based microporous frameworks (PTC-236(Δ) and PTC-236(Λ)) were easily prepared by a post-assembly reaction. PTC-236 has rich recognition sites provided by the Ti4 L6 moieties, chiral channels and high framework stability, affording a single-crystal-to-single-crystal transformation for guest structure analyses. Thus it was successfully utilized for the recognition and separation of isomeric molecules. This study provides a new approach for the orderly combination of well-defined MOCs into functional porous frameworks.

7.
J Cell Biochem ; 124(2): 221-238, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36502529

RESUMO

Although the aberrant activity of fibroblast growth factor receptor 3 (FGFR3) is implicated in various cancers, the reported kinase inhibitors of FGFR3 tend to cause side effects resulting from the inhibitory activity on vascular endothelial growth factor receptor 2 (VEGFR2). Therefore, it is necessary to find a novel high-selective inhibitor of FGFR3 over VEGFR2 from the small-molecule compound database. In this study, integrated virtual screening protocols were established to screen for selective inhibitors of FGFR3 over VEGFR2 in Drugbank and Asinex databases by combining three-dimensional pharmacophore model, molecular docking, molecular dynamics (MD) simulation, and molecular mechanics Poisson-Boltzmann surface area (MMPBSA) calculations. Finally, it is found that Asinex-5082, as an octahydropyrrolo[3,2-b] pyridin derivative, has larger binding free energy with FGFR3 (-39.3 kcal/mol) than reference drug Erdafitinib (-29.9 kcal/mol), while cannot bind with VEGFR2, resulting in considerable inhibitory selectivity. This is because Asinex-5082, unlike Erdafitinib, has not m-dimethoxybenzene with large steric hindrance, thus can enter the larger ATP-binding pocket of FGFR3 with DFG-in conformation to form hydrophobic interaction with residues Met529, Ile539, and Tyr557 as well as hydrogen bond with Ala558. On the other hand, due to the fact that the benzodioxane and N-heterocyclic rings are connected by carbonyl (C=O), Asinex-5082 cannot rotate freely so as to enter the smaller ATP binding pocket of VEGFR2 on the DFG-out conformation. The lead molecule Asinex-5082 may facilitate the rational design and development of novel selective inhibitors of FGFR3 over VEGFR2 as anticancer drugs.


Assuntos
Inibidores de Proteínas Quinases , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Simulação de Acoplamento Molecular , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Fator A de Crescimento do Endotélio Vascular , Simulação de Dinâmica Molecular , Trifosfato de Adenosina , Ligantes
8.
Dalton Trans ; 51(33): 12494-12501, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35916624

RESUMO

The development of stable, Earth-abundant, and high-activity molecular water oxidation catalysts under acidic and neutral conditions remains a great challenge. Here, the use of N-heterocyclic carbene (NHC)-based iron(III) complex 1 {[phenyl(tris(3-methylimidazol-1-ylidene))borate]2Fe(III)}+ as a catalyst for water oxidation under acidic and neutral conditions was investigated. Two iron(II) carbene complexes, 2 {[2,6-bis(3-methylimidazolium-1-yl)pyridine]2Fe}2+ and 3 {[2,6-bis(3-methylimidazolium-1-yl)pyridine-4-carboxylic acid]2Fe}2+, were also used for comparison. A series of experiments demonstrate that complex 1 has excellent performance in terms of both catalytic activity and stability. In addition, the faradaic efficiency and turnover frequency (TOF) reach 95.0% and 2.8 s-1, respectively. An overpotential of ca. 490 mV is obtained at pH 1.5. Density functional theory (DFT) calculations indicate that dehydrogenation is the potential-determining step (PDS) in water oxidation. Complex 1 has a lower free energy barrier in this process than 2 and 3. High-valent Fe species are further proven in 1 by spectroelectrochemical measurements, which are crucial in promoting water oxidation. This study is expected to contribute to the development of homogeneous water oxidation catalysis under acidic and neutral conditions.

9.
Cell Mol Life Sci ; 79(7): 394, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35786773

RESUMO

Iron is an essential micro-element, involved in multiple biological activities in vertebrates. Excess iron accumulation has been identified as an important mediator of lipid deposition. However, the underlying mechanisms remain unknown. In the present study, we found that a high-iron diet significantly increased intestinal iron content and upregulated the mRNA expression of two iron transporters (zip14 and fpn1). Intestinal iron overload increased lipogenesis, reduced lipolysis and promoted oxidative stress and mitochondrial dysfunction. Iron-induced lipid accumulation was mediated by hypoxia-inducible factor-1 α (HIF1α), which was induced in response to mitochondrial oxidative stress following inhibition of prolyl hydroxylase 2 (PHD2). Mechanistically, iron promoted lipid deposition by enhancing the DNA binding capacity of HIF1α to the pparγ and fas promoters. Our results provide experimental evidence that oxidative stress, mitochondrial dysfunction and the HIF1α-PPARγ pathway are critical mediators of iron-induced lipid deposition.


Assuntos
Ferro , PPAR gama , Animais , Lipídeos , Mitocôndrias , Estresse Oxidativo , PPAR gama/genética
10.
Dalton Trans ; 51(16): 6162-6165, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35383809

RESUMO

We herein report the discovery of inorganic toroidal and capsule titanium oxysulfate clusters by ionothermal synthesis. The ratio between geometrically different anions (tetrahedral SO42-vs. pseudo-tetrahedral PO33-) shows an interesting influence on cluster structure formation.

11.
Angew Chem Int Ed Engl ; 61(20): e202201430, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35253345

RESUMO

Herein, we present a stable water-soluble cobalt complex supported by a dianionic 2,2'-([2,2'-bipyridine]-6,6'-diyl)bis(propan-2-ol) ligand scaffold, which is a rare example of a high-oxidation species, as demonstrated by structural, spectroscopic and theoretical data. Electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements revealed that the CoIV center of the mononuclear complex in the solid state resides in the high spin state (sextet, S=5/2). The complex can effectively catalyze water oxidation via a single-site water nucleophilic attack pathway with an overpotential of only 360 mV in a phosphate buffer with a pH of 6. The key intermediate toward water oxidation was speculated based on theoretical calculations and was identified by in situ spectroelectrochemical experiments. The results are important regarding the accessibility of high-oxidation state metal species in synthetic models for achieving robust and reactive oxidation catalysis.


Assuntos
Cobalto , Água , Catálise , Cobalto/química , Espectroscopia de Ressonância de Spin Eletrônica , Oxirredução , Água/química
12.
Inorg Chem ; 61(12): 5017-5024, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35286073

RESUMO

In this study, with the assistance of quaternary ammonium salts we have successfully prepared a new family of salicylate-stabilized heterobimetallic Pb-Ti-oxo clusters, including H(TEA)[Pb2Ti6(µ2-O)2(µ3-O)2(OiPr)4(PA)2(Sal)6(NO3)2] (PTC-321; TEA = tetraethylammonium; HOiPr = isopropanol; H2PA = phenylphosphonic acid; H2Sal = salicylic acid), {PbTi3(µ2-O)(µ3-O)(OiPr)2(PA)(Sal)3(DMF)·CH3CN}n (PTC-322; DMF = dimethylformamide), {PbTi5(µ3-O)6(Sal)3(CH3COO)2(DMF)(OiPr)2}n (PTC-323), [Pb2Ti4(Sal)6(EtO)2(OiPr)6(HOiPr)2]·CH3NH2 (PTC-324; EtOH = CH3CH2OH), H[Pb4Ti9(µ2-O)2(µ3-O)(µ4-O)6(Sal)7(OiPr)13] (PTC-325), and Pb2Ti12(µ2-O)3(µ3-O)3(µ4-O)4(Sal)4(OEt)24 (PTC-326). Single-crystal X-ray diffraction studies demonstrate that the {Ti3Pb(Sal)3} unit acts as the building block to constitute the diverse assembly of PTC-321-PTC-323. Thereinto, the clusters in PTC-322 and PTC-323 are connected into infinite one-dimensional chains. Furthermore, the solvent effects have facilitated the heterobimetallic Pb-Ti-oxo clusters into various configurations in PTC-323-PTC-326. Solid-state ultraviolet-visible spectroscopy analysis indicates that the optical absorption bands of these compounds shift effectively toward the visible-light region, and they were also employed as electrode precursors to investigate their visible-light-driven photocurrent response.

13.
Antioxid Redox Signal ; 37(7-9): 417-436, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35293223

RESUMO

Aims: Excessive manganese (Mn) exposure is toxic, and induces lipid deposition, but the underlying mechanisms remain elusive. Herein, we explored how dietary Mn supplementation affects lipid deposition and metabolism in the intestine of vertebrates using the yellow catfish Pelteobagrus fulvidraco as the model. Results: High-Mn (H-Mn) diet increased intestinal Mn content, promoted lipid accumulation and lipogenesis, and inhibited lipolysis. In addition, it induced oxidative stress, upregulated metal-response element-binding transcription factor-1 (MTF-1), and peroxisome proliferator-activated receptor gamma (PPARγ) protein expression in the nucleus, induced PPARγ acetylation, and the interaction between PPARγ and retinoid X receptor alpha (RXRα), while it downregulated sirtuin 1 (SIRT1) expression and activity. Mechanistically, Mn activated the MTF-1/divalent metal transporter 1 (DMT1) pathway, increased Mn accumulation in the mitochondria, and induced oxidative stress. This in turn promoted lipid deposition via deacetylation of PPARγ at K339 by SIRT1. Subsequently, PPARγ mediated Mn-induced lipid accumulation through transcriptionally activating fatty acid translocase, stearoyl-CoA desaturase 1, and perilipin 2 promoters. Innovation: These studies uncover a previously unknown mechanism by which Mn induces lipid deposition in the intestine via the oxidative stress-SIRT1-PPARγ pathway. Conclusion: High dietary Mn intake activates MTF-1/DMT1 and oxidative stress pathways. Oxidative stress-mediated PPARγ deacetylation at K339 site contributes to increased lipid accumulation. Our results provided a direct link between Mn and lipid metabolism via the oxidative stress-SIRT1-PPARγ axis. Antioxid. Redox Signal. 37, 417-436.


Assuntos
Peixes-Gato , Sirtuína 1 , Animais , Peixes-Gato/metabolismo , Intestinos , Metabolismo dos Lipídeos , Lipídeos , Manganês/metabolismo , Manganês/farmacologia , Estresse Oxidativo , PPAR gama/metabolismo , Sirtuína 1/metabolismo
14.
Chem Commun (Camb) ; 58(30): 4759-4762, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35342916

RESUMO

Two unprecedented Sn/Cd-oxo clusters, including non-alkyltin SnII2SnIV2Cd4 and alkyltin SnIV2Cd12, have been constructed using triethanolamine and inorganic or organic tin precursors, respectively. Comparative electrocatalytic CO2 reduction experiments show that the presence of non-alkyl and variable-valent tin centres could greatly improve the catalytic activities.


Assuntos
Cádmio , Estanho , Etanolaminas
15.
Front Microbiol ; 13: 792876, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295310

RESUMO

One of the major mechanisms underlying plant growth-promoting rhizobacteria (PGPR) is the lowering of ethylene level in plants by deamination of 1-aminocyclopropane-1-carboxylic acid (ACC) in the environment. In the present study, using ACC as the sole nitrogen source, we screened seven ACC deaminase-producing bacterial strains from rhizosphere soils of tea plants. The strain with the highest ACC deaminase activity was identified as Serratia marcescens strain JW-CZ2. Inoculation of this strain significantly increased shoot height and stem diameter of tea seedlings, displaying significant promotive effects. Besides, S. marcescens strain JW-CZ2 displayed high ACC deaminase activities in wide ranges of ACC concentration, pH, and temperature, suggesting the applicable potential of JW-CZ2 as a biofertilizer. Genome sequencing indicated that clusters of orthologous groups of proteins (COG) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of JW-CZ2 mainly included amino acid transport and metabolism, transcription, carbohydrate transport and metabolism, inorganic ion transport and metabolism, and membrane transport. Moreover, genes in relation to phosphate solubilization, indole acetic acid (IAA) production, and siderophore were observed in the genome of JW-CZ2, and further experimental evidence demonstrated JW-CZ2 could promote solubilization of inorganic phosphate, inhibit growth of pathogenic fungi, and produce IAA and siderophore. These aspects might be major reasons underlying the plant growth-promoting function of JW-CZ2. Overall, this study provides a new S. marcescens strain, which has applicable potential as a promising biofertilizer.

16.
Environ Sci Technol ; 56(4): 2407-2420, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35107266

RESUMO

Due to many special characteristics, zinc oxide nanoparticles (ZnO NPs) are widely used all over the world, leading to their wide distribution in the environment. However, the toxicities and mechanisms of environmental ZnO NP-induced changes of physiological processes and metabolism remain largely unknown. Here, we found that addition of dietary ZnO NPs disturbed hepatic Zn metabolism, increased hepatic Zn and lipid accumulation, downregulated lipolysis, induced oxidative stress, and activated mitophagy; N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN, Zn2+ ions chelator) alleviated high ZnO NP-induced Zn and lipid accumulation, oxidative stress, and mitophagy. Mechanistically, the suppression of mitochondrial oxidative stress attenuated ZnO NP-activated mitophagy and ZnO NP-induced lipotoxicity. Taken together, our study elucidated that mitochondrial oxidative stress mediated ZnO NP-induced mitophagy and lipotoxicity; ZnO NPs could be dissociated to free Zn2+ ions, which partially contributed to ZnO NP-induced changes in oxidative stress, mitophagy, and lipid metabolism. Our study provides novel insights into the impacts and mechanism of ZnO NPs as harmful substances inducing lipotoxicity of aquatic organisms, and accordingly, metabolism-relevant parameters will be useful for the risk assessment of nanoparticle materials in the environment.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Animais , Água Doce , Lipídeos , Nanopartículas Metálicas/toxicidade , Mitocôndrias/metabolismo , Mitofagia , Nanopartículas/toxicidade , Estresse Oxidativo , Óxido de Zinco/toxicidade
17.
Inorg Chem ; 61(3): 1385-1390, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35014787

RESUMO

Exploring new structural types of polyoxotitanium clusters (PTCs), especially those containing classical polyoxometalates structures, has always been the focus of research in the field of metal-oxo clusters. In this work, we present the synthesis and characterization of three prismatic PTCs: namely, Ti8(µ2-O)3(µ4-O)2(OnPr)6(HOnPr)2(L1)8 (PTC-237; H2L1 = 3,5-di-tert-butylcatechol), Ti12(µ2-O)6(µ3-O)8(OnPr)6(L2)12(L3)2 (PTC-238; HL2 = 1-adamantanecarboxylic acid, HL3 = 2-picolinic acid), and [Ti18(µ2-O)4(µ3-O)16(µ5-O)2(OiPr)18(L3)8](L3)2 (PTC-239). Single-crystal X-ray diffraction analyses indicate that the construction of these prismatic PTCs is based on a stepwise interlayer assembly of {Ti3} and {Ti4} substructures. The diameters of their core skeletons are in the range between 0.9 and 1.3 nm. In particular, lacunary Linqvist-like {Ti4} and {Ti5} building units are found to exist in the structures of PTC-237 and PTC-239. According to the solid-state UV-vis diffuse reflectance measurements, the absorption band of 3,5-di-tert-butylcatecholate-functionalized PTC-237 shifts toward the visible-light region, giving a smaller optical band gap of 1.56 eV in comparison to PTC-238 (3.36 eV) and PTC-239 (3.25 eV).

18.
Free Radic Biol Med ; 180: 95-107, 2022 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-35045311

RESUMO

Ferroptosis is a regulated form of cell death induced by iron (Fe)-dependent lipid peroxidation. At present, the underlying molecular mechanisms remain elusive. Herein, we hypothesized that mitochondria and the NRF2 (transcription factor nuclear factor E2-related factor 2) are potential mediators of ferroptosis, considering their well-established involvement in the oxidative stress pathway. We found that a high iron diet increased hepatic iron content and promoted glutathione (GSH) depletion, lipid peroxidation and oxidative stress. Dietary iron overload also decreased mRNA and protein expression levels of glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11), and increased mRNA and protein expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), which are all markers of ferroptosis. Consistent with ferroptosis, iron overload promoted lipid peroxidation and the generation of mitochondrial reactive oxygen species (ROS), and decreased the mitochondrial membrane potential (MMP). Pre-treatment with deferoxamine mesylate (DFO, an iron chelator) alleviated ROS generation and lipid peroxidation, indicating a causative link between iron overload and lipid peroxidation. Suppression of mitochondrial oxidative stress attenuated ferroptosis. Experiments with HEK293T cells revealed that Fe-induced ferroptosis involved direct inhibition of NRF2 binding to antioxidant response elements (AREs) within the promoters of the gpx4 and slc7a11 genes, which in turn induced transcriptional silencing. In conclusion, our study provided a direct link between mitochondrial oxidative stress and ferroptosis via the NRF2-ARE pathway.


Assuntos
Ferroptose , Fator 2 Relacionado a NF-E2 , Ferroptose/genética , Células HEK293 , Humanos , Peroxidação de Lipídeos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia
19.
Zhonghua Nan Ke Xue ; 28(6): 524-528, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-37477470

RESUMO

OBJECTIVE: To observe the clinical efficacy of the "water-pathogen" theory-based Juanyin Tongluo Recipe (JTR) in the treatment of varicocele (VC) complicated with oligozoospermia and its effects on the semen parameters, sperm morphology, sperm DNA fragmentation index (DFI) and testis volume of the patient. METHODS: Ninety-two VC patients complicated with oligozoospermia were randomly assigned to receive JTR (n = 47) and Maizhiling Tablets (the control group, n = 45), respectively, both for three months, followed by comparisons of the clinical effects, total sperm count, sperm motility, percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), sperm DNA fragmentation index (DFI) and testis volume of the patients before and after medication, and the pregnancy rate after treatment between the two groups. RESULTS: The total rate of effectiveness was significantly higher in the JTR than in the control group (87.23% vs 68.89%, P < 0.05). Compared with the baseline, the patients showed dramatic improvement after treated with JTR in the sperm count (ï¼»16.35 ± 3.52ï¼½ vs ï¼»43.82 ± 6.02ï¼½ ×106, P < 0.05), sperm motility (ï¼»17.37 ± 6.76ï¼½% vs ï¼»36.68 ± 11.32ï¼½%, P < 0.05), PMS (ï¼»13.42 ± 5.62ï¼½% vs ï¼»31.03 ± 7.47ï¼½%, P < 0.05), MNS (ï¼»1.91 ± 0.13ï¼½% vs ï¼»4.06 ± 0.11ï¼½%, P < 0.05), and sperm DFI (ï¼»43.32 ± 7.84ï¼½% vs ï¼»26.98 ± 6.87ï¼½%, P < 0.05), and even better than in the control group (sperm count ï¼»15.78 ± 3.84ï¼½ vs ï¼»31.53 ± 5.62ï¼½ ×106, P < 0.05; sperm motility ï¼»19.41 ± 6.24ï¼½% vs ï¼»31.32 ± 9.73ï¼½%, P < 0.05; PMS ï¼»14.01 ± 4.98ï¼½% vs ï¼»20.71 ± 6.49ï¼½%, P < 0.05; MNS ï¼»1.88 ± 0.14ï¼½% vs ï¼»3.12 ± 0.09ï¼½%, P < 0.05; sperm DFI ï¼»41.42 ± 9.62ï¼½% vs ï¼»34.13 ± 5.73ï¼½%, P < 0.05; sperm DFI, P < 0.05). And the rate of natural pregnancy was significantly higher in the JTR group than in the control (40.43% vs 20%, P < 0.05). No statistically significant difference, however, was observed in the testis volume before and after treatment between the JTR group (ï¼»11.53 ± 1.24ï¼½ vs ï¼»10.89 ± 1.17ï¼½ ml, P > 0.05) and the control (ï¼»10.94 ± 1.34ï¼½ vs ï¼»10.65 ± 1.52ï¼½ ml, P > 0.05). CONCLUSION: Juanyin Tongluo Recipe can increase the total sperm count, sperm motility, percentages of PMS and MNS and sperm DFI, and improve the rate of natural pregnancy in VC patients complicated with oligozoospermia.


Assuntos
Infertilidade Masculina , Oligospermia , Varicocele , Gravidez , Feminino , Humanos , Masculino , Sêmen , Infertilidade Masculina/etiologia , Infertilidade Masculina/genética , Oligospermia/tratamento farmacológico , Motilidade dos Espermatozoides , Varicocele/complicações , Varicocele/tratamento farmacológico , Fragmentação do DNA , Espermatozoides , Análise do Sêmen , Contagem de Espermatozoides
20.
Zhonghua Nan Ke Xue ; 28(5): 432-436, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-37477483

RESUMO

OBJECTIVE: To observe the therapeutic efficacy of Baihe Yuzi Prescription (BYP) in the treatment of clinical syndrome-free asthenospermia and its effects on semen parameters, sperm DNA fragmentation index (DFI) and the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in the sperm. METHODS: We randomly divided 112 patients with clinical syndrome-free asthenospermia into a control group (n = 55) and an experimental group (n = 57), the former treated orally with L-carnitine liquid combined with vitamin E capsules and the latter with BYP in addition, both for 3 months. After treatment, we obtained the total sperm count, sperm motility, percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), sperm DFI and expression of CFTR in the sperm, and compared the above parameters between the two groups of patients before and after medication. RESULTS: The total effectiveness rate was significantly higher in the experimental group (82.46%) than in the control (65.45%) (P < 0.05). Compared with the baseline, the patients in the experimental group showed significant improvement after treatment in the total sperm count (��53.5��3.5�� vs ��86.5��3.9�� ��106, P < 0.05), sperm motility (��23.5��3.5��% vs ��38.8��3.7��%, P < 0.05), PMS (��20.1��3.2��% vs ��30.3��3.3��%, P < 0.05), MNS (��2.3��0.3��% vs ��3.9��0.4��%, P < 0.05), sperm DFI (��37.3��3.1��% vs ��25.2��3.4��%, P < 0.05) and the expression of CFTR (P < 0.05), and even better improvement than the controls in sperm motility (��23.8��3.7��% vs ��30.2��3.4��%, P < 0.05), PMS (��19.6��3.1��% vs ��25.3��2.9��%, P < 0.05), MNS (��2.4��0.4��% vs ��3.1��0.3��%, P < 0.05), and sperm DFI (��36.6��3.3��% vs ��30.3��3.1��%, P < 0.05). The total sperm count and the expression of CFTR, however, were not significantly improved in the control group after treatment (P > 0.05). CONCLUSION: Baihe Yuzi Prescription can increase sperm count and motility, improve sperm morphology and DFI in patients with clinical syndrome-free asthenospermia, which may be related to the up-regulated expression of CFTR in the sperm.


Assuntos
Astenozoospermia , Sêmen , Humanos , Masculino , Contagem de Espermatozoides , Regulador de Condutância Transmembrana em Fibrose Cística , Motilidade dos Espermatozoides , Espermatozoides , Astenozoospermia/tratamento farmacológico , Fragmentação do DNA
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