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1.
Small ; 20(8): e2306100, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37817367

RESUMO

Herein, the construction of a heterostructured 1D/3D CoN-Co2 N@NF (nickel foam) electrode used for thermodynamically favorable hydrazine oxidation reaction (HzOR), as an alternative to sluggish anodic oxygen evolution reaction (OER) in water splitting for hydrogen production, is reported. The electrode exhibits remarkable catalytic activities, with an onset potential of -0.11 V in HzOR and -71 mV for a current density of 10 mA cm-2 in hydrogen evolution reaction (HER). Consequently, an extraordinary low cell voltage of 53 mV is required to achieve 10 mA cm-2 for overall hydrazine splitting in a two-electrode system, demonstrating significant energy-saving advantages over conventional water splitting. The HzOR proceeds through the 4e- reaction pathway to release N2 while the 1e- pathway to emit NH3 is uncompetitive, as evidenced by differential electrochemical mass spectrometric measurements. The X-ray absorption spectroscopy, in situ Raman spectroscopy, and theoretical calculations identify cobalt nitrides rather than corresponding oxides/(oxy)hydroxides as catalytic species for HzOR and illustrate advantages of heterostructured CoN-Co2 N in optimizing adsorption energies of intermediates/reagents and promoting catalytic activities toward both HzOR and HER. The CoN-Co2 N@NF is also an excellent supercapacitive material, exhibiting an increased specific capacity (938 F g-1 at 1 A g-1 ) with excellent cycling stability (95.8%, 5000 cycles).

2.
J Transl Med ; 21(1): 639, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726857

RESUMO

BACKGROUND: Progressive peritoneal fibrosis is a worldwide public health concern impacting patients undergoing peritoneal dialysis (PD), yet there is no effective treatment. Our previous study revealed that a novel compound, micheliolide (MCL) inhibited peritoneal fibrosis in mice. However, its mechanism remains unclear. Brahma-related gene 1 (BRG1) is a key contributor to organ fibrosis, but its potential function in PD-related peritoneal fibrosis and the relationship between MCL and BRG1 remain unknown. METHODS: The effects of MCL on BRG1-induced fibrotic responses and TGF-ß1-Smads pathway were examined in a mouse PD model and in vitro peritoneal mesothelial cells. To investigate the targeting mechanism of MCL on BRG1, coimmunoprecipitation, MCL-biotin pulldown, molecular docking and cellular thermal shift assay were performed. RESULTS: BRG1 was markedly elevated in a mouse PD model and in peritoneal mesothelial cells cultured in TGF-ß1 or PD fluid condition. BRG1 overexpression in vitro augmented fibrotic responses and promoted TGF-ß1-increased-phosphorylation of Smad2 and Smad3. Meanwhile, knockdown of BRG1 diminished TGF-ß1-induced fibrotic responses and blocked TGF-ß1-Smad2/3 pathway. MCL ameliorated BRG1 overexpression-induced peritoneal fibrosis and impeded TGF-ß1-Smad2/3 signaling pathway both in a mouse PD model and in vitro. Mechanically, MCL impeded BRG1 from recognizing and attaching to histone H3 lysine 14 acetylation by binding to the asparagine (N1540) of BRG1, in thus restraining fibrotic responses and TGF-ß1-Smad2/3 signaling pathway. After the mutation of N1540 to alanine (N1540A), MCL was unable to bind to BRG1 and thus, unsuccessful in suppressing BRG1-induced fibrotic responses and TGF-ß1-Smad2/3 signaling pathway. CONCLUSION: Our research indicates that BRG1 may be a crucial mediator in peritoneal fibrosis and MCL targeting N1540 residue of BRG1 may be a novel therapeutic strategy to combat PD-related peritoneal fibrosis.


Assuntos
Diálise Peritoneal , Fibrose Peritoneal , Animais , Camundongos , Modelos Animais de Doenças , Simulação de Acoplamento Molecular , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/tratamento farmacológico , Fator de Crescimento Transformador beta1
3.
Ann Surg Oncol ; 30(13): 8223-8230, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37535270

RESUMO

BACKGROUND: This study aimed to compare the efficacy and postoperative quality of life for patients with esophageal cancer treated by either the modified or the traditional thoracolaparoscopic McKeown procedure. METHODS: This retrospective case-control study included 269 patients with esophageal cancer admitted to three medical centers in China from February 2020 to August 2022. The patients were divided according to surgical method into the layered hand-sewn end-to-end invagination anastomosis group (modified group) and the traditional hand anastomosis group (traditional group). Propensity score-matching (PSM) was used to maintain balance and comparability between the two groups. RESULTS: The differences in age and tumor location between the patients in the traditional and modified groups were statistically significant. After PSM, the aforementioned factors were statistically insignificant. After PSM, each group had 101 patients. The modified group showed the greater advantage in terms of postoperative hospital stay (P = 0.036), incidence of anastomotic leak (P = 0.009), and incidence of gastroesophageal reflux (P < 0.001), and the difference was statistically significant. The results of the Quality of Life Questionnaire Core 30 (QLQ-C30) and Quality of Life Questionnaire Oesophageal Cancer Module 18 (QLQ-OES18) scales showed that the modified group also had the advantage over the traditional group in terms of physical function, overall health status, loss of appetite, eating, reflux, obstruction, and loss of appetite scores at the first and third months after surgery. CONCLUSION: The modified thoraco-laparoscopic McKeown procedure is a safe and effective surgical approach that can significantly reduce the incidence of postoperative anastomotic leak and gastroesophageal reflux, shorten the postoperative hospital stay, and improve the postoperative quality of life for patients with esophageal cancer.


Assuntos
Neoplasias Esofágicas , Refluxo Gastroesofágico , Laparoscopia , Humanos , Fístula Anastomótica/etiologia , Qualidade de Vida , Estudos Retrospectivos , Estudos de Casos e Controles , Pontuação de Propensão , Laparoscopia/métodos , Anastomose Cirúrgica/métodos , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/cirurgia , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia
4.
Mol Cell ; 60(4): 661-75, 2015 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-26585387

RESUMO

Elucidating the tumorigenic mechanism of R-2-hydroxyglutarate (R-2HG) is critical for determining how NADP(+)-IDH mutations cause cancer. Here we report that R-2HG induces cancerous metabolism and apoptosis resistance through promoting hypersuccinylation. By competitive inhibition of the mitochondrial tricarboxylic acid cycle enzyme succinate dehydrogenase (SDH), R-2HG preferentially induced succinyl-CoA accumulation and hypersuccinylation in the mitochondria. IDH1 mutation-bearing glioma samples and cells were hypersuccinylated in the mitochondria. IDH1 mutation or SDH inactivation resulted in hypersuccinylation, causing respiration inhibition and inducing cancerous metabolism and mitochondrial depolarization. These mitochondrial dysfunctions induced BCL-2 accumulation at the mitochondrial membrane, leading to apoptosis resistance of hypersuccinylated cells. Relief of hypersuccinylation by overexpressing the desuccinylase SIRT5 or supplementing glycine rescued mitochondrial dysfunctions, reversed BCL-2 accumulation, and slowed the oncogenic growth of hypersuccinylated IDH1(R132C)-harboring HT1080 cells. Thus, R-2HG-induced hypersuccinylation contributes to the tumorigenicity of NADP(+)-IDH mutations, suggesting the potential of hypersuccinylation inhibition as an intervention for hypersuccinylation-related tumors.


Assuntos
Glutaratos/farmacologia , Isocitrato Desidrogenase/genética , Mitocôndrias/efeitos dos fármacos , Mutação , Neoplasias Experimentais/metabolismo , Ácido Succínico/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Células HEK293 , Humanos , Camundongos , Mitocôndrias/metabolismo , Neoplasias Experimentais/genética , Succinato Desidrogenase/antagonistas & inibidores
5.
Angew Chem Int Ed Engl ; 62(3): e202214959, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36307930

RESUMO

The renewable-electricity-driven CO2 reduction to formic acid would contribute to establishing a carbon-neutral society. The current catalyst suffers from limited activity and stability under high selectivity and the ambiguous nature of active sites. Herein, we report a powerful Bi2 S3 -derived catalyst that demonstrates a current density of 2.0 A cm-2 with a formate Faradaic efficiency of 93 % at -0.95 V versus the reversible hydrogen electrode. The energy conversion efficiency and single-pass yield of formate reach 80 % and 67 %, respectively, and the durability reaches 100 h at an industrial-relevant current density. Pure formic acid with a concentration of 3.5 mol L-1 has been produced continuously. Our operando spectroscopic and theoretical studies reveal the dynamic evolution of the catalyst into a nanocomposite composed of Bi0 clusters and Bi2 O2 CO3 nanosheets and the pivotal role of Bi0 -Bi2 O2 CO3 interface in CO2 activation and conversion.

6.
Ecotoxicol Environ Saf ; 230: 113149, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34974361

RESUMO

Sedum plumbizincicola, a cadmium (Cd) hyperaccumulating herbaceous plant, can accumulate large amounts of Cd in the above-ground tissues without being poisoned. However, the molecular mechanisms regulating the processes are not fully understood. In this study, Transcriptional and proteomic analyses were integrated to investigate the response of S. plumbizincicola plants to Cd stress and to identify key pathways that are potentially responsible for Cd tolerance and accumulation. A total of 630 DAPs (differentially abundant proteins, using fold change >1.5 and adjusted p-value <0.05) were identified from Tandem Mass Tag (TMT)- based quantitative proteomic profiling, which were enriched in processes including phenylpropanoid biosynthesis, protein processing in endoplasmic reticulum, and biosynthesis of secondary metabolites. Combined with the previous transcriptomic study, 209 genes and their corresponding proteins showed the identical expression pattern. The identified genes/proteins revealed the potential roles of several metabolism pathways, including phenylpropanoid biosynthesis, oxidative phosphorylation, phagosome, and glutathione metabolism, in mediating Cd tolerance and accumulation. Lignin staining and Cd accumulation assay of the transgenic lines over-expressing a selected Cd up-regulated gene SpFAOMT (Flavonoid 3',5'-methyltransferase) showed its functions in adapting to Cd stress, and provided insight into its role in lignin biosynthesis and Cd accumulation in S. plumbizincicola during Cd stress.

7.
Chem Soc Rev ; 50(23): 12897-12914, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34609390

RESUMO

The electrocatalytic reduction of CO2 with H2O to multi-carbon (C2+) compounds, in particular, C2+ olefins and oxygenates, which have versatile applications in the chemical and energy industries, holds great potential to mitigate the depletion of fossil resources and abate carbon emissions. There are two major routes for the electrocatalytic CO2 reduction to C2+ compounds, i.e., the direct route and the indirect route via CO. The electrocatalytic CO2 reduction to CO has been commercialised with solid oxide electrolysers, making the indirect route via CO to C2+ compounds also a promising alternative. This tutorial review focuses on the similarities and differences in the electrocatalytic CO2 and CO reduction reactions (CO2RR and CORR) into C2+ compounds, including C2H4, C2H5OH, CH3COO- and n-C3H7OH, over Cu-based catalysts. First, we introduce the fundamental aspects of the two electrocatalytic reactions, including the cathode and anode reactions, electrocatalytic reactors and crucial performance parameters. Next, the reaction mechanisms, in particular, the C-C coupling mechanism, are discussed. Then, efficient catalysts and systems for these two reactions are critically reviewed. We analyse the key factors that determine the selectivity, activity and stability for the electrocatalytic CO2RR and CORR. Finally, the opportunities, challenges and future trends in the electrocatalytic CO2RR and CORR are proposed. These insights will offer guidance for the design of industrial-relevant catalysts and systems for the synthesis of C2+ olefins and oxygenates.


Assuntos
Dióxido de Carbono , Carbono , Catálise , Compostos Orgânicos
8.
Clin Sci (Lond) ; 135(15): 1873-1895, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34318888

RESUMO

Although accelerated cellular senescence is closely related to the progression of chronic kidney disease (CKD) and renal fibrosis, the underlying mechanisms remain largely unknown. Here, we reported that tubular aberrant expression of Brahma-related gene 1 (BRG1), an enzymatic subunit of the SWItch/Sucrose Non-Fermentable complex, is critically involved in tubular senescence and renal fibrosis. BRG1 was significantly up-regulated in the kidneys, predominantly in tubular epithelial cells, of both CKD patients and unilateral ureteral obstruction (UUO) mice. In vivo, shRNA-mediated knockdown of BRG1 significantly ameliorated renal fibrosis, improved tubular senescence, and inhibited UUO-induced activation of Wnt/ß-catenin pathway. In mouse renal tubular epithelial cells (mTECs) and primary renal tubular cells, inhibition of BRG1 diminished transforming growth factor-ß1 (TGF-ß1)-induced cellular senescence and fibrotic responses. Correspondingly, ectopic expression of BRG1 in mTECs or normal kidneys increased p16INK4a, p19ARF, and p21 expression and senescence-associated ß-galactosidase (SA-ß-gal) activity, indicating accelerated tubular senescence. Additionally, BRG1-mediated pro-fibrotic responses were largely abolished by small interfering RNA (siRNA)-mediated p16INK4a silencing in vitro or continuous senolytic treatment with ABT-263 in vivo. Moreover, BRG1 activated the Wnt/ß-catenin pathway, which further inhibited autophagy. Pharmacologic inhibition of the Wnt/ß-catenin pathway (ICG-001) or rapamycin (RAPA)-mediated activation of autophagy effectively blocked BRG1-induced tubular senescence and fibrotic responses, while bafilomycin A1 (Baf A1)-mediated inhibition of autophagy abolished the effects of ICG-001. Further, BRG1 altered the secretome of senescent tubular cells, which promoted proliferation and activation of fibroblasts. Taken together, our results indicate that BRG1 induces tubular senescence by inhibiting autophagy via the Wnt/ß-catenin pathway, which ultimately contributes to the development of renal fibrosis.


Assuntos
Autofagia , Senescência Celular , DNA Helicases/metabolismo , Células Epiteliais/metabolismo , Nefropatias/metabolismo , Túbulos Renais/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Citocinas/metabolismo , DNA Helicases/genética , Modelos Animais de Doenças , Células Epiteliais/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Células HEK293 , Humanos , Nefropatias/etiologia , Nefropatias/patologia , Túbulos Renais/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas Nucleares/genética , Ratos , Fatores de Transcrição/genética , Obstrução Ureteral/complicações
9.
FASEB J ; 34(10): 13300-13316, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32786113

RESUMO

Podocyte injury is the primary cause of glomerular injury in diabetic nephropathy (DN). Advanced oxidation protein products (AOPPs), the triggers and markers of oxidative stress in DN, have been linked to podocyte damage. However, the underlying mechanism is not yet clear. Here, we investigated the potential role of FOXO3a, a key transcription factor in the response to stress, in mediating AOPPs-induced podocyte injury. We found that FOXO3a expression was increased in the glomeruli of kidney biopsies from patients with DN and it was positively correlated with proteinuria. The serum from patients with DN significantly increased FOXO3a and its downstream genes FasL and Bim, thereby inducing the high level of cleaved caspase3 and the loss of nephrin and podocin expressions in podocytes. Blockade of AOPPs signaling by a neutralizing antibody against the receptor of advanced glycation end products (αRAGE) abolished the effect of DN serum on podocytes, confirming the pathogenic role of AOPPs in DN serum. Downregulation of FOXO3a decreased AOPPs-induced podocyte apoptosis and restored the levels of podocyte markers nephrin and podocin, and upregulation of FOXO3a exacerbated these changes in podocytes after AOPPs treatment. Furthermore, FOXO3a specifically activated proapoptotic genes in podocytes only in the presence of AOPPs. Mechanistically, AOPPs increased the FOXO3a protein levels by inhibiting their autophagic degradation in a ROS/mTOR-dependent manner. Moreover AOPPs activated the accumulated FOXO3a by maintaining FOXO3a in the nucleus, and this process was dependent on ROS-mediated AKT signaling deactivation. These studies suggest that FOXO3a plays a critical role in mediating AOPPs-induced podocyte injury and reveal a new mechanistic linkage of oxidative stress, FOXO3a activation and podocyte injury in DN.


Assuntos
Nefropatias Diabéticas/metabolismo , Proteína Forkhead Box O3/metabolismo , Estresse Oxidativo , Podócitos/metabolismo , Produtos da Oxidação Avançada de Proteínas/sangue , Produtos da Oxidação Avançada de Proteínas/metabolismo , Animais , Apoptose , Autofagia , Biomarcadores/sangue , Biomarcadores/metabolismo , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Proteína Forkhead Box O3/genética , Produtos Finais de Glicação Avançada/sangue , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/sangue , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Podócitos/patologia , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Receptor para Produtos Finais de Glicação Avançada/metabolismo
10.
Analyst ; 145(23): 7695-7700, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-32985629

RESUMO

A photoelectrochemical (PEC) aptasensor based on silver nanoparticle/BiOCl (AgNP/BiOCl) composites was constructed for detecting chloramphenicol (CAP). The surface-plasmon resonance (SPR) effect of AgNPs can focus the incident light and promote the migration and separation of the photogenerated carriers of AgNP/BiOCl composites. As a result, the AgNP/BiOCl composites showed an enhanced PEC performance compared to that of pure BiOCl. A PEC CAP aptasensor was fabricated using AgNP/BiOCl composites as photoactive materials and a CAP aptamer as a recognition element. The PEC aptasensor exhibited a broad linear response range (0.2 pM-10 nM), a low limit of determination (0.08 pM), satisfactory selectivity, stability, and reproducibility to meet the practical analysis requirements. This work demonstrates that the PEC CAP aptasensor has a promising prospect in environmental assays.

11.
Mikrochim Acta ; 186(11): 737, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31673790

RESUMO

A self-powered photoelectrochemical (PEC) aptamer probe is presented for the determination of oxytetracycline (OTC). The assay is based on the use of g-C3N4 and NiO nanocrystals (NCs) which form a heterojunction. The latter was prepared by two-step hydrothermal pyrolysis by using the ionic liquid 1-hydroxyethyl-3-methylimidazole chloride which functions as a morphological template to form NiO NCs. The heterojunction exhibits much better electronic conductivity, wider absorption range, higher electron-hole-separation productivity, and stronger photocurrent compared to plain g-C3N4. The heterojunction was adopted to construct a self-powered PEC aptamer probe for OTC detection. An OTC-binding aptamer was immobilized on the heterojunction and the probe was constructed. The aptamer on the probe binding with OTC can form steric hindrance for transmitting of electrons and cause the PEC signal change depending on the OTC concentration. The photocurrent decreases with increasing OTC concentration in the 0.01 to 100 nM concentration range and its detection limit is 4 pM (at S/N = 3). Graphical abstract Schematic representation of a self-powered photochemical aptamer probe. The probe performs enhanced ability for oxytetracycline (OTC) determination due to the formation of NiO nanocrystals/g-C3N4 (NiO NCs/g-C3N4) heterojunction and the specification recognition of the aptamer.

13.
Molecules ; 23(9)2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30227644

RESUMO

A novel 2'-F,4'-C-OMe⁻arabinouridine (araU) was successfully synthesized and introduced into oligonucleotides. The oligonucleotide containing 2'-F,4'-C-OMe⁻araU exhibited improved nuclease resistance and RNA hybridizing selective ability relative to 2'-F⁻araU. In particular, when 2'-F,4'-C-OMe⁻araU inserted into C⁻H⋯F⁻C bonding-favorable 5'⁻uridine⁻purine⁻3' steps, the modified oligonucleotide showed remarkable binding affinity and selectivity to RNA complements. Thus, 2'-F,4'-C-OMe⁻araU has valuable antisense properties and can be used as novel chemical modification for antisense therapeutic strategy.


Assuntos
Oligonucleotídeos Antissenso/síntese química , Oligonucleotídeos Antissenso/farmacologia , Uridina/síntese química , Uridina/farmacologia , Estabilidade Enzimática , Desnaturação de Ácido Nucleico , Oligonucleotídeos Antissenso/química , Diester Fosfórico Hidrolases/metabolismo , Venenos de Serpentes/enzimologia , Uridina/química
14.
Apoptosis ; 21(10): 1125-43, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27401922

RESUMO

The objective of our study was to assess the radioprotective effect of flavonoids extracted from Rosa roxburghii Tratt (FRT) and investigate the role of Bcl-2(Ca(2+))/Caspase-3/PARP-1 pathway in radiation-induced apoptosis. Cells and mice were exposed to (60)Co γ-rays at a dose of 6 Gy. The radiation treatment induced significant effects on tissue pathological changes, apoptosis, Ca(2+), ROS, DNA damage, and expression levels of Bcl-2, Caspase-3 (C-Caspase-3), and PARP-1. The results showed that FRT acted as an antioxidant, reduced DNA damage, corrected the pathological changes of the tissue induced by radiation, promoted the formation of spleen nodules, resisted sperm aberration, and protected the thymus. FRT significantly reduced cell apoptosis compared with the irradiation group. The expression of Ca(2+) and C-Caspase-3 was decreased after FRT treatment compared with the radiation-treated group. At the same time, expression of prototype PARP-1 and Bcl-2 increased, leading to a decrease in the percentage of apoptosis cells in FRT treatment groups. We conclude that FRT acts as a radioprotector. Apoptosis signals were activated via the Bcl-2(Ca(2+))/Caspase-3/PARP-1 pathway in irradiated cells and FRT inhibited this pathway of apoptosis by down-regulation of C-Caspase-3 and Ca(2+) and up-regulation of prototype PARP-1 and Bcl-2.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Flavonoides/administração & dosagem , Extratos Vegetais/administração & dosagem , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Protetores contra Radiação/administração & dosagem , Rosa/química , Animais , Apoptose/efeitos da radiação , Caspase 3/genética , Raios gama , Humanos , Masculino , Camundongos , Poli(ADP-Ribose) Polimerase-1/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética
15.
Int J Mol Sci ; 17(2)2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26828481

RESUMO

Icariin, a pharmacologically active component isolated from the Chinese herb Epimedium, has been shown to improve spatial learning and memory abilities in Alzheimer's disease (AD) rats through inhibition of Aß production and tau protein hyperphosphorylation. However, the potential mechanism of icariin-induced protective effects against mitochondrial dysfunctions in AD still remains unclear. In the present study, we investigated the effect of icariin on the modulation of mitochondrial transport and distribution in primary hippocampal cultures from triple-transgenic (3× Tg) AD mice. The results showed that icariin enhanced mitochondrial motility and increased mitochondrial index and mitochondrial length and size in the diseased neurons. Additionally, the expression of the key mitochondrial enzyme, pyruvate dehydrogenase-E1α (PDHE1α), and the post synaptic density protein 95 (PSD95), was preserved in AD neurons after icariin treatment, accompanied by a downregulation of Aß and phosphorylated tau expression in the corresponding areas. Further study showed that icariin treatment resulted in a decrease in mitochondrial fission protein dynamin-related protein 1 (Drp1) and an increase in fusion protein Mitofusin 2 (Mfn2). These data indicate that icariin can promote mitochondrial transport, protect mitochondria against fragmentation and preserve the expression of mitochondrial and synaptic functional proteins in AD neurons. Thus, icariin may be a potential therapeutic complement for AD and other mitochondrial malfunction-related neuronal degenerative diseases.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Flavonoides/administração & dosagem , Hipocampo/citologia , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Modelos Animais de Doenças , Flavonoides/farmacologia , Camundongos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Tamanho Mitocondrial/efeitos dos fármacos , Neurônios/metabolismo , Proteínas tau/metabolismo
16.
Yao Xue Xue Bao ; 51(8): 1271-80, 2016 08.
Artigo em Chinês | MEDLINE | ID: mdl-29905991

RESUMO

Chemical modification is critical for the therapeutic applications of antisense oligonucleotides. Novel 4'-C-MOE and 2'-fluoro- modified monomer 2'-F-4'-C-MOE-ara U and its epimeric 2'-F-4'-C-MOE-r U were synthesized from 2'-fluorinated arabinourine (2'-F-ara U) and 2'-fluorouridine(2'-F-r U), respectively. Their phosphoramidites were synthesized and successfully incorporated into oligodeoxynucleotides. The mismatch discrimination ability of these unnatural monomers and their effect on thermal stability were evaluated in the context of ds DNA and DNA-RNA chimeras. The thermal denaturation studies showed that the incorporation of 2'-F-4'-C-MOE-ara U led to enhanced binding affinity to complementary RNA strand and almost equivalent binding ability to complementary DNA, when compared with 2'-F-4'-C-MOE-r U and 2'-F-ara U modified duplexes. Especially a C-H(…)F-C pseudohydrogen bond was supposed to contribute more binding affinity at uridine-purine steps, meanwhile, 2'-F-4'-C-MOE-ara U had almost the same base discriminatory ability as uridine in ds DNA and DNA-RNA chimeras, while 2'-F-4'-C-MOE-r U was found to have only moderate RNA hybridization ability. However, 2'-F-4'-C-MOE-araU at 3'-end of oligonucleotide could not led to more nuclease hydrolytic stability than that with 2'-F-4'-C-MOE-r U modification. These results demonstrated the feasibility of C4'-MOE modification on 2'-F-ANA and the dramatic effects of the 2'-F substituent, which provides a new approach for further chemical modification of antisense drugs.


Assuntos
Oligodesoxirribonucleotídeos/química , Oligonucleotídeos Antissenso/química , Uridina/química , DNA , Compostos Organofosforados/síntese química , RNA
17.
Bioorg Med Chem ; 22(1): 325-33, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24315191

RESUMO

Several dibenzocyclooctatetraene derivatives (5-7) and related biphenyls (8-11) were designed, synthesized, and evaluated for inhibition of cancer cell growth and the NF-κB signaling pathway. Compound 5a, a dibenzocyclooctatetraene succinimide, was discovered as a potent inhibitor of the NF-κB signaling pathway with significant antitumor activity against several human tumor cell lines (GI50 1.38-1.45 µM) and was more potent than paclitaxel against the drug-resistant KBvin cell line. Compound 5a also inhibited LPS-induced NF-κB activation in RAW264.7 cells with an IC50 value of 0.52 µM, prevented IκB-α degradation and p65 nuclear translocation, and suppressed LPS-induced NO production in a dose-dependent manner. The antitumor data in cellular assays indicated that relative positions and types of substituents on the dibenzocyclooctatetraene or acyclic biphenyl as well as torsional angles between the two phenyls are of primary importance to antitumor activity.


Assuntos
Anticarcinógenos/química , Compostos de Bifenilo/química , NF-kappa B/antagonistas & inibidores , Anticarcinógenos/uso terapêutico , Produtos Biológicos , Humanos , NF-kappa B/metabolismo , Transdução de Sinais
18.
Artigo em Inglês | MEDLINE | ID: mdl-39048537

RESUMO

BACKGROUND: Individuals with schizophrenia tend to have negative coping styles and low levels of self-esteem, but it is unclear whether coping styles and self-esteem levels are altered in people in the prodromal phase of psychosis. AIMS: The study was designed to assess the role of coping style and self-esteem in the context of different phases of schizophrenia. METHODS: Recurrent Schizophrenia (ReSch), first-episode schizophrenia patients (FEP), genetic-high risk for psychosis (GHR) patients, and healthy controls (HC) (40 per group) were subjected to in-person clinical interviews. The results of these interviews were then used to gauge coping style and self-esteem using the Coping Styles Questionnaire (CSQ) and the Rosenberg's Self-Esteem Scale (RSES). Data were analyzed through ANCOVAs and logistic regression analyses. RESULTS: The results found that positive coping style (CSQ problem-solving and CSQ seeking for help) generally decline with progression through the HC, GHR, and FEP groups, while negative coping style (CSQ fantasy, CSQ repression and CSQ self-blame) generally increase with progression through the HC, GHR, and FEP groups (except that GHR group was slightly lower than HC group in CSQ self-blame). Results for members of ReSch group were in line with those of members of the FEP group in coping style. At the level of self-esteem, the GHR group was similar to the HC group and significantly higher than the FEP group and the ReSch group. Logistic regression analyses indicated that GHR group patients exhibited increased negative coping styles (CSQ fantasy) relative to members of the HC group, but had greater Positive coping style (CSQ problem-solving) than did members of the FEP group. DISCUSSION: These findings suggest that both GHR individuals experience impaired negative coping styles which expands the understanding of the psychological characteristics of the prodromal group. Further explorations are warranted to develop optimal psychosocial interventions.

19.
ACS Nano ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39051970

RESUMO

Electrorefinery of polybutylene terephthalate (PBT) waste plastic, specifically conversion of a PBT-derived 1,4-butanediol (BDO) monomer into value-added succinate coupled with H2 production, emerges as an auspicious strategy to mitigate severe plastic pollution. Herein, we report the synthesis of Mn-doped NiNDA nanosheets (NDA: 2,6-naphthalenedicarboxylic acid), a metal-organic framework (MOF) through a ligand exchange method, and its utilization for electrocatalytic BDO oxidation to succinate. Interestingly, the transformation of doped layered-hydroxide (d-LH) precursors to MOF promotes BDO oxidation while hindering the competitive oxygen evolution reaction. Experimental and theoretical results indicate that the MOF has a higher affinity (i.e., alcoholophilic) for BDO than the d-LH, while Mn doping into NiNDA results in electron accumulation at Ni sites with an upward shift in the d-band center and convenient spin-dependent charge transfer, which are all beneficial for BDO oxidation. The as-constructed two-electrode membrane-electrode assembly (MEA) flow cell, by coupling BDO oxidation and hydrogen evolution reaction, attains an industrial current density of 1.5 A cm-2@1.82 V at 50 °C, corresponding to a specific energy consumption of 3.68 kWh/Nm3 H2. This represents an energy saving of >25% for hydrogen production on an industrial scale compared to conventional water electrolysis (∼5 kWh/Nm3 H2) in addition to the production of valuable chemicals.

20.
Carbohydr Polym ; 345: 122583, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39227111

RESUMO

Herein, the effects of temperature cycling (4 °C/50 °C/100 °C) on the recrystallization, physicochemical properties, and digestibility of debranched starch (DBS) were investigated. Temperature cycling involved heating DBS to 100 °C to dissociate weak heat-sensitive crystalline structures and cooling to 4 °C to induce the rapid growth of crystal nuclei, followed by maintaining the temperature at 50 °C to promote orderly crystalline growth. This procedure aimed to increase the degree of crystalline structure in recrystallized DBS, thereby resulting in DBS that was heat- and digestion-resistant. Temperature cycling increased the dissociation temperature of DBS, and temperatures of up to 114.8 °C were attained after five cycling times. With increasing cycles, the crystalline structure of DBS transitioned from B-type to the more robust and compact A-type, and the crystallinity increased to ∼81.9 % (after seven cycles). Raman and Fourier transform infrared (FTIR) spectra indicated that temperature cycling enhanced the short-range ordered structure of DBS. Moreover, in vitro digestion experiments demonstrated that the resistant starch content of DBS increased to ∼61.9 % after eight cycles. To summarize, this study demonstrated a green and effective method for preparing heat-and digestion-resistant recrystallized DBS, which can be used for developing dietary supplements and low gastrointestinal staples.

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