Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 110
Filtrar
1.
Plant Cell Environ ; 47(8): 2895-2910, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38623040

RESUMO

Phytoplasmic SAP11 effectors alter host plant architecture and flowering time. However, the exact mechanisms have yet to be elucidated. Two SAP11-like effectors, SJP1 and SJP2, from 'Candidatus Phytoplasma ziziphi' induce shoot branching proliferation. Here, the transcription factor ZjTCP7 was identified as a central target of these two effectors to regulate floral transition and shoot branching. Ectopic expression of ZjTCP7 resulted in enhanced bolting and earlier flowering than did the control. Interaction and expression assays demonstrated that ZjTCP7 interacted with the ZjFT-ZjFD module, thereby enhancing the ability of these genes to directly bind to the ZjAP1 promoter. The effectors SJP1 and SJP2 unravelled the florigen activation complex by specifically destabilising ZjTCP7 and ZjFD to delay floral initiation. Moreover, the shoot branching of the ZjTCP7-SRDX transgenic Arabidopsis lines were comparable to those of the SJP1/2 lines, suggesting the involvement of ZjTCP7 in the regulation of shoot branching. ZjTCP7 interacted with the branching repressor ZjBRC1 to enhance suppression of the auxin efflux carrier ZjPIN3 expression. ZjTCP7 also directly bound to and upregulated the auxin biosynthesis gene ZjYUCCA2, thereby promoting auxin accumulation. Our findings confirm that ZjTCP7 serves as a bifunctional regulator destabilised by the effectors SJP1 and SJP2 to modulate plant development.


Assuntos
Arabidopsis , Flores , Phytoplasma , Brotos de Planta , Plantas Geneticamente Modificadas , Phytoplasma/fisiologia , Flores/crescimento & desenvolvimento , Flores/genética , Brotos de Planta/crescimento & desenvolvimento , Arabidopsis/genética , Arabidopsis/microbiologia , Arabidopsis/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Regiões Promotoras Genéticas/genética , Ácidos Indolacéticos/metabolismo
2.
J Org Chem ; 89(5): 3345-3358, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38372225

RESUMO

In this study, a modular approach toward cyclic sulfoximines and sulfondiimines via palladium-catalyzed intramolecular C-H/C-C activation reactions was reported. Various 1,2-benzothiazines including bicyclic, tricyclic, highly fused ones, ones of the seven-membered ring, along with 1,2-benzothiazine 1-imines were accessed in good yields. KIE experiment demonstrated that the C-H bond cleavage at the position ortho to the sulfoximine group is not the rate-determining step in the coupling reaction.

3.
J Org Chem ; 89(8): 5442-5457, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38567881

RESUMO

In this study, concise, efficient, and modular hydrophosphinylation and hydroamidation of gem-difluorocyclopropenes were disclosed in a mild and transition-metal-free pattern. Through this approach, phosphorus, and nitrogen-containing gem-difluorocyclopropanes were produced in moderate to good yields with excellent regio- and diastereoselectivity. Readily available gem-difluorocyclopropenes and nucleophilic reagents, along with inexpensive inorganic bases, were employed. Multiple synthetic applications, including gram-scale and derivatization reactions and modification of bioactive molecules, were subsequently elaborated.

4.
Environ Sci Technol ; 58(16): 7228-7236, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38551367

RESUMO

The development of electrocatalysts that can efficiently reduce nitrate (NO3-) to ammonia (NH3) has garnered increasing attention due to their potential to reduce carbon emissions and promote environmental protection. Intensive efforts have focused on catalyst development, but a thorough understanding of the effect of the microenvironment around the reactive sites of the catalyst is also crucial to maximize the performance of the electrocatalysts. This study explored an electrocatalytic system that utilized quaternary ammonium surfactants with a range of alkyl chain lengths to modify an electrode made of carbon nanotubes (CNT), with the goal of regulating interfacial wettability toward NO3- reduction. Trimethyltetradecylammonium bromide with a moderate alkyl chain length created a very hydrophobic interface, which led to a high selectivity in the production of NH3 (∼87%). Detailed mechanistic investigations that used operando Fourier-transform infrared (FTIR) spectroscopy and online differential electrochemical mass spectrometry (DEMS) revealed that the construction of a hydrophobic modified CNT played a synergistic role in suppressing a side reaction involving the generation of hydrogen, which would compete with the reduction of NO3-. This electrocatalytic system led to a favorable process for the reduction of NO3- to NH3 through a direct electron transfer pathway. Our findings underscore the significance of controlling the hydrophobic surface of electrocatalysts as an effective means to enhance electrochemical performance in aqueous media.


Assuntos
Amônia , Eletrodos , Nanotubos de Carbono , Nitratos , Molhabilidade , Amônia/química , Nanotubos de Carbono/química , Nitratos/química , Oxirredução , Catálise
5.
Environ Sci Technol ; 58(4): 2144-2152, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38234209

RESUMO

The electrocatalytic nitrate reduction reaction (NO3RR) has recently emerged as a promising technique for readily converting aqueous nitrate (NO3-) pollutants into valuable ammonia (NH3). It is vital to thoroughly understand the mechanism of the reaction to rationally design and construct advanced electrocatalytic systems that can effectively and selectively drive the NO3RR. There are several natural enzymes that incorporate molybdenum (Mo) and that can activate NO3-. Based on this, a cadmium (Cd) single-atom anchored Mo2TiC2Tx electrocatalyst (referred to as CdSA-Mo2TiC2Tx) through the NO3RR to generate NH3 was rationally designed and demonstrated. In an H-type electrolysis cell and at a current density of 42.5 mA cm-2, the electrocatalyst had a Faradaic efficiency of >95% and an impressive NH3 yield rate of 48.5 mg h-1 cm-2. Moreover, the conversion of NO3- to NH3 on the CdSA-Mo2TiC2Tx surface was further revealed by operando attenuated total reflection Fourier-transform infrared spectroscopy and an electrochemical differential mass spectrometer. The electrocatalyst significantly outperformed Mo2TiC2Tx as well as reported state-of-the-art catalysts. Density functional theory calculations revealed that CdSA-Mo2TiC2Tx decreased the ability of the d-p orbital to hybridize with NH3* intermediates, thereby decreasing the activation energy of the potential-determining step. This work not only highlights the application prospects of heavy metal single-atom catalysts in the NO3RR but also provides examples of bio-inspired electrocatalysts for the synthesis of NH3.


Assuntos
Amônia , Nitratos , Cádmio , Molibdênio , Eletrodos
6.
J Biochem Mol Toxicol ; 38(1): e23630, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38229308

RESUMO

Hepatic ischemia-reperfusion (IR) injury is a complex systemic process causing a series clinical problem. C/EBPα is a key transcription factor for hepatocyte function, but its role and mechanism in regulating hepatic IR injury are largely unknown. Occluding portal vein and hepatic artery was used to establish a mouse model of hepatic IR injury. C/EBPα expression was decreased in IR-injured liver compared with the sham, accompanied by increased contents of serum alanine transaminase (ALT), aspartate transaminase (AST), high mobility group box-1, and proportion of hepatic cells. Oxygen and glucose deprivation/recovery (OGD/R) was used to establish a cellular hepatic IR model in WRL-68 hepatocytes in vitro, and C/EBPα was overexpressed in the hepatocytes to evaluate its effect on hepatic IR injury. OGD/R promoted oxidative stress, cell apoptosis and endoplasmic reticulum (ER) stress in hepatocytes, which was reversed by C/EBPα overexpression. Then, we found that C/EBPα promoted histone deacetylase 1 (HDAC1) transcription through binding to HDAC1 promoter. Moreover, HDAC1 deacetylated the activating transcription factor 4 (ATF4), a key positive regulator of ER stress. Trichostatin-A (an HDAC inhibitor) or ATF4 overexpression reversed the improvement of C/EBPα on OGD/R-induced ER stress and hepatocyte dysfunction. 4-Phenylbutyric acid (an endoplasmic reticulum stress inhibitor) also reversed the hepatic IR injury induced by ATF4 overexpression. Finally, lentivirus-mediated C/EBPα overexpression vector was applied to administrate hepatic IR mice, and the results showed that C/EBPα overexpression ameliorated IR-induced hepatic injury, manifesting with reduced ALT/AST, oxidative stress and ER stress. Altogether, our findings suggested that C/EBPα ameliorated hepatic IR injury by inhibiting ER stress via HDAC1-mediated deacetylation of ATF4 promoter.


Assuntos
Fator 4 Ativador da Transcrição , Traumatismo por Reperfusão , Animais , Camundongos , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/farmacologia , Apoptose , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/farmacologia , Estresse do Retículo Endoplasmático , Histona Desacetilase 1/metabolismo , Histona Desacetilase 1/farmacologia , Fígado/metabolismo , Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo
7.
Neurosurg Rev ; 47(1): 116, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483647

RESUMO

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Resultado do Tratamento , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/etiologia , Embolização Terapêutica/efeitos adversos , Pontuação de Propensão , Estudos Retrospectivos , Estudos de Coortes , Procedimentos Endovasculares/efeitos adversos
8.
Environ Sci Technol ; 57(28): 10458-10466, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37387677

RESUMO

The growth of renewable energy industries and the ongoing need for fertilizer in agriculture have created a need for sustainable production of ammonia (NH3) using low-cost, environment-friendly techniques. The electrocatalytic nitrate (NO3-) reduction reaction (NO3RR) has the potential to improve both the management of environmental nitrogen and the recycling of synthetic nutrients. However, NO3RR is frequently hindered by the incomplete NO3- conversion, sluggish reaction kinetics, and suppression of the hydrogen evolution reaction (HER). Inspired by specific local electronic structures that are adjustable for single-atom catalysts, this work presents a nanohybrid electrocatalytic filter with iron single atoms (FeSA) immobilized on MXene. The fabricated FeSA/MXene filter exhibited maximum NH3 Faradaic efficiency and selectivity (82.9 and 99.2%, respectively) that were higher than those for filters made of Fe nanoparticles anchored on MXene (FeNP/MXene) (69.2 and 81.3%, respectively) and MXene alone (32.8 and 52.4%, respectively), measured at an initial pH of 7 and an applied potential of -1.4 V vs Ag/AgCl. Density functional theory calculations revealed that, compared to the FeNP/MXene filter, the FeSA/MXene filter prevented the competition from the HER and reduced the activation energy of the potential-limiting step (*NO to *NHO) that made the NH3 synthesis thermodynamically favorable . This work highlights an alternative strategy for achieving a synergistic NO3- removal and nutrient recovery with durable catalytic activity and stability.


Assuntos
Amônia , Nitratos , Eletrodos , Hidrogênio , Ferro
9.
Molecules ; 28(14)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37513184

RESUMO

In this study, pristine kiwi peel (KP) and nitric acid modified kiwi peel (NA-KP) based adsorbents were prepared and evaluated for selective removal of cationic dye. The morphology and chemical structure of KP and NA-KP were fully characterized and compared, and results showed nitric acid modification introduced more functional groups. Moreover, the adsorption kinetics and isotherms of malachite green (MG) by KP and NA-KP were investigated and discussed. The results showed that the adsorption process of MG onto KP followed a pseudo-second-order kinetic model and the Langmuir isotherm model, while the adsorption process of MG onto NA-KP followed a pseudo-first-order kinetic model and the Freundlich isotherm model. Notably, the Langmuir maximum adsorption capacity of NA-KP was 580.61 mg g-1, which was superior to that of KP (297.15 mg g-1). Furthermore, thermodynamic studies demonstrated the feasible, spontaneous, and endothermic nature of the adsorption process of MG by NA-KP. Importantly, NA-KP showed superior selectivity to KP towards cationic dye MG against anionic dye methyl orange (MO). When the molar ratio of MG/MO was 1:1, the separation factor (αMG/MO) of NA-KP was 698.10, which was 5.93 times of KP. In addition, hydrogen bonding, π-π interactions, and electrostatic interaction played important roles during the MG adsorption process by NA-KP. This work provided a low-cost, eco-friendly, and efficient option for the selective removal of cationic dye from dyeing wastewater.


Assuntos
Corantes , Poluentes Químicos da Água , Corantes/química , Adsorção , Ácido Nítrico , Corantes de Rosanilina/química , Termodinâmica , Cinética , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio
10.
Mol Biol Evol ; 38(12): 5292-5308, 2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34562099

RESUMO

Long-lived plants face the challenge of ever-increasing mutational burden across their long lifespan. Early sequestration of meristematic stem cells is supposed to efficiently slow down this process, but direct measurement of somatic mutations that accompanies segregated cell lineages in plants is still rare. Here, we tracked somatic mutations in 33 leaves and 22 adventitious roots from 22 stem-cuttings across eight major branches of a shrub willow (Salix suchowensis). We found that most mutations propagated separately in leaves and roots, providing clear evidence for early segregation of underlying cell lineages. By combining lineage tracking with allele frequency analysis, our results revealed a set of mutations shared by distinct branches, but were exclusively present in leaves and not in roots. These mutations were likely propagated by rapidly dividing somatic cell lineages which survive several iterations of branching, distinct from the slowly dividing axillary stem cell lineages. Leaf is thus contributed by both slowly and rapidly dividing cell lineages, leading to varied fixation chances of propagated mutations. By contrast, each root likely arises from a single founder cell within the adventitious stem cell lineages. Our findings give straightforward evidence that early segregation of meristems slows down mutation accumulation in axillary meristems, implying a plant "germline" paralog to the germline of animals through convergent evolution.


Assuntos
Salix , Animais , Linhagem da Célula/genética , Meristema/genética , Mutação , Folhas de Planta/genética , Raízes de Plantas/genética , Salix/genética
11.
Funct Integr Genomics ; 22(6): 1113-1126, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36372834

RESUMO

The maintenance of epigenetic characteristics is essential for the normal growth and development of organisms. The maintenance of DNA methylation is an important way to maintain the epigenetic characteristics of organisms. DNMT1 is a core enzyme that maintains intracellular DNA methylation, and UHRF1, as a cofactor of DNMT1, plays an important role in the regulation of DNA methylation by DNMT1. The maintenance of DNA methylation mediated by UHRF1-DNMT1 complex is involved in the regulation of many vital activities. This review describes the whole molecular process of UHRF1-DNMT1 pathway from the opening of inhibitory structure to the end of maintenance methylation in detail and lists some latest biological research progress related to this pathway in the development of early embryonic, maintenance of pluripotency of embryonic stem cells, regulation of expression of imprinted genes, inactivation of X chromosome, and development of cancer. Finally, put forward some problems remained to be solved at present and new thoughts.


Assuntos
DNA (Citosina-5-)-Metiltransferases , Metilação de DNA , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Processamento de Proteína Pós-Traducional
12.
Radiology ; 304(2): 372-382, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35438564

RESUMO

Background The Woven EndoBridge (WEB) device was explicitly designed for wide-neck intracranial bifurcation aneurysms. Small-scale reports have evaluated the off-label use of WEB devices for the treatment of sidewall aneurysms, with promising outcomes. Purpose To compare the angiographic and clinical outcomes of the WEB device for the treatment of sidewall aneurysms compared with the treatment of bifurcation aneurysms. Materials and Methods A retrospective review of the WorldWideWEB Consortium, a synthesis of retrospective databases spanning from January 2011 to June 2021 at 22 academic institutions in North America, South America, and Europe, was performed to identify patients with intracranial aneurysms treated with the WEB device. Characteristics and outcomes were compared between bifurcation and sidewall aneurysms. Propensity score matching (PSM) was used to match by age, pretreatment ordinal modified Rankin Scale score, ruptured aneurysms, location of aneurysm, multiple aneurysms, prior treatment, neck, height, dome width, daughter sac, and incorporated branch. Results A total of 683 intracranial aneurysms were treated using the WEB device in 671 patients (median age, 61 years [IQR, 53-68 years]; male-to-female ratio, 1:2.5). Of those, 572 were bifurcation aneurysms and 111 were sidewall aneurysms. PSM was performed, resulting in 91 bifurcation and sidewall aneurysms pairs. No significant difference was observed in occlusion status at last follow-up, deployment success, or complication rates between the two groups. Conclusion No significantly different outcomes were observed following the off-label use of the Woven EndoBridge, or WEB, device for treatment of sidewall aneurysms compared with bifurcation aneurysms. The correct characterization of the sidewall aneurysm location, neck angle, and size is crucial for successful treatment and lower retreatment rate. © RSNA, 2022 See also the editorial by Hetts in this issue.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Aneurisma Roto/terapia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
13.
Environ Toxicol ; 37(10): 2540-2551, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35841383

RESUMO

Lysyl-oxidase-like 3 (LOXL3) was reported to be essential in epithelial-mesenchymal transition (EMT) of cancers. However, the role of LOXL3 in hepatocellular carcinoma (HCC) remained unclear. In this study, we explored clinical significance, biological functions, and regulatory mechanisms of LOXL3 in HCC. Our study found that LOXL3 expression was markedly associated with the tumor size and clinical stage of HCC, and it was highly expressed in tumor tissues of metastatic HCC patients. High expression of LOXL3 predicted a poor prognosis of HCC. TGF-ß1 treatment elevated LOXL3 protein expression and cell invasion, and reduced cell apoptosis in HCC cell lines (SMMC-7721 and Huh-7), while downregulation of LOXL3 reversed the promotive effects of TGF-ß1 treatment on LOXL3 protein expression and cell invasion, and the inhibitory effect on cell apoptosis. Mechanistically, LOXL3 interacted with snail family transcriptional repressor 1 (Snail1) through STRING database and RIP assay, and Snail1 bound to ubiquitin-specific peptidase 4 (USP4) promoter by JASPAR database, luciferase reporter gene and Co-IP assays. Overexpression of USP4 reversed the inhibitory effect of LOXL3 silence on EMT in HCC cells through deubiquitinating and stabilizing the expression of Snail1. Moreover, LOXL3-promoted HCC EMT through Wnt/ß-catenin/Snail1 signaling pathway. In vivo study revealed that silence of LOXL3-inhibited HCC tumor growth. In conclusion, LOXL3 silence inhibited HCC invasion and EMT through Snail1/USP4-mediated circulation loop and Wnt/ß-catenin signaling pathway.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
14.
Int J Mol Sci ; 23(16)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36012144

RESUMO

Metastatic triple-negative breast cancer (mTNBC), a highly aggressive and malignant tumor, currently lacks an effective treatment. There has been some progress in the treatment of mTNBC with programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) immunotherapy in recent years. The combination of PD-1/PD-L1 inhibitors with other therapies is a noteworthy treatment strategy. Immunotherapy in combination with chemotherapy or small-molecule inhibitors still faces many challenges. Additionally, there are some new immunotherapy targets in development. We aimed to further evaluate the effectiveness and usefulness of immunotherapy for treating mTNBC and to propose new immunotherapy strategies. This review explains the rationale and results of existing clinical trials evaluating PD-1/PD-L1 inhibitors alone or in combination for the treatment of mTNBC. For patients with aggressive tumors and poor health, PD-1/PD-L1 inhibitors, either alone or in combination with other modalities, have proven to be effective. However, more research is needed to explore more effective immunotherapy regimens that will lead to new breakthroughs in the treatment of mTNBC.


Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Fatores Imunológicos , Imunoterapia/métodos , Receptor de Morte Celular Programada 1 , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
15.
J Cell Physiol ; 236(2): 931-945, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32583428

RESUMO

Ischemia reperfusion (I/R)-induced acute kidney injury (AKI) is a common and serious condition. Irisin, an exercise-induced hormone, improves mitochondrial function and reduces reactive oxygen species (ROS) production. Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis and its inactivation aggravates renal I/R injury by inducing ROS production. However, the effect of irisin on GPX4 and I/R-induced AKI is still unknown. To study this, male adult mice were subjected to renal I/R by occluding bilateral renal hilum for 30 min, which was followed by 24 hr reperfusion. Our results showed serum irisin levels were decreased in renal I/R mice. Irisin (250 µg/kg) treatment alleviated renal injury, downregulated inflammatory response, improved mitochondrial function, and reduced ER stress and oxidative stress after renal I/R, which were associated with upregulation of GPX4. Treated with RSL3 (a GPX4 inhibitor) abolished irisin's protective effect. Thus, irisin attenuates I/R-induced AKI through upregulating GPX4.


Assuntos
Injúria Renal Aguda/metabolismo , Fibronectinas/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Ferroptose/fisiologia , Inflamação/metabolismo , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Reperfusão/métodos , Regulação para Cima/fisiologia
16.
BMC Infect Dis ; 21(1): 415, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947336

RESUMO

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease among children in developed countries, in which the resulting coronary artery (CA) abnormalities cause myocardial ischemia, infarction, and death. Prompt diagnosis was essential, and supplemental information should be used to assist the diagnosis when classical clinical criteria are incomplete. The elevated levels of serum transaminases in most KD patients are mild. Herein, a case of atypical KD child with severely elevated transaminase was reported. CASE PRESENTATION: A child with clinical manifestations of fever, high C-reactive protein (CRP) and severely elevated transaminases was reported. The treatment effect of antibiotic and liver-protecting drugs was not satisfactory. A bilateral diffuse dilation of the CA was detected on echocardiography on day 5 of the illness; thus, atypical KD was diagnosed. Elevated transaminases declined rapidly to normal after the treatment of intravenous immunoglobulin (IVIG). A 1-month follow-up revealed that CA returned to normal, and 2-month, 6-months, and 1-year follow-up revealed the child was in good general health. CONCLUSIONS: This case highlighted that atypical KD clinical symptoms were diverse, and severely elevated transaminases might provide a clue to healthcare providers for the diagnosis and management of atypical KD.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/etiologia , Transaminases/sangue , Proteína C-Reativa/análise , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Ecocardiografia , Febre/tratamento farmacológico , Febre/etiologia , Humanos , Lactente , Masculino
17.
J Cell Mol Med ; 24(22): 13081-13092, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32954626

RESUMO

Liver steatosis is associated with increased ischaemia reperfusion (I/R) injury. Our previous studies have shown that irisin, an exercise-induced hormone, mitigates I/R injury via binding to αVß5 integrin. However, the effect of irisin on I/R injury in steatotic liver remains unknown. Kindlin-2 directly interacts with ß integrin. We therefore suggest that irisin protects against I/R injury in steatotic liver via a kindlin-2 dependent mechanism. To study this, hepatic steatosis was induced in male adult mice by feeding them with a 60% high-fat diet (HFD). At 12 weeks after HFD feeding, the mice were subjected to liver ischaemia by occluding partial (70%) hepatic arterial/portal venous blood for 60 minutes, which was followed by 24 hours reperfusion. Our results showed HFD exaggerated I/R-induced liver injury. Irisin (250 µg/kg) administration at the beginning of reperfusion attenuated liver injury, improved mitochondrial function, and reduced oxidative and endoplasmic reticulum stress in HFD-fed mice. However, kindlin-2 inhibition by RNAi eliminated irisin's direct effects on cultured hepatocytes. In conclusion, irisin attenuates I/R injury in steatotic liver via a kindlin-2 dependent mechanism.


Assuntos
Proteínas do Citoesqueleto/metabolismo , Fibronectinas/metabolismo , Hepatopatias/metabolismo , Proteínas Musculares/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático , Fígado Gorduroso/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo
18.
J Cell Mol Med ; 24(1): 996-1009, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31701659

RESUMO

Disruption of the gut barrier results in severe clinical outcomes with no specific treatment. Metabolic disorders and destruction of enterocytes play key roles in gut barrier dysfunction. Irisin is a newly identified exercise hormone that regulates energy metabolism. However, the effect of irisin on gut barrier function remains unknown. The therapeutic effect of irisin on gut barrier dysfunction was evaluated in gut ischemia reperfusion (IR). The direct effect of irisin on gut barrier function was studied in Caco-2 cells. Here, we discovered that serum and gut irisin levels were decreased during gut IR and that treatment with exogenous irisin restored gut barrier function after gut IR in mice. Meanwhile, irisin decreased oxidative stress, calcium influx and endoplasmic reticulum (ER) stress after gut IR. Moreover, irisin protected mitochondrial function and reduced enterocyte apoptosis. The neutralizing antibody against irisin significantly aggravated gut injury, oxidative stress and enterocyte apoptosis after gut IR. Further studies revealed that irisin activated the AMPK-UCP 2 pathway via binding to the integrin αVß5 receptor. Inhibition of integrin αVß5, AMPK or UCP 2 abolished the protective role of irisin in gut barrier function. In conclusion, exogenous irisin restores gut barrier function after gut IR via the integrin αVß5-AMPK-UCP 2 pathway.


Assuntos
Epitélio/metabolismo , Fibronectinas/administração & dosagem , Enteropatias/prevenção & controle , Mucosa Intestinal/metabolismo , Receptores de Vitronectina/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Estresse do Retículo Endoplasmático , Epitélio/patologia , Fibronectinas/metabolismo , Enteropatias/etiologia , Enteropatias/patologia , Mucosa Intestinal/lesões , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais
19.
BMC Infect Dis ; 20(1): 145, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066406

RESUMO

BACKGROUND: Pyogenic liver abscess (PLA) is an inflammatory disease with increasing incidence. When it occurs with diabetes mellitus (DM), the risk of recurrence and mortality may increase. However, the effect of DM on the short-term prognosis of PLA patients after hospitalization remained unknown. METHODS: Two hundred twenty-seven PLA patients who received treatment at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to January 2018 were retrospectively enrolled. They were divided into two groups as the DM group (n = 61) and the Non-DM group (n = 166). In the DM group, HbA1C level < 7% was considered to be good-control of glycaemia (n = 23). The clinical characteristics and overall short-term survival were analyzed. RESULTS: The proportion of PLA patients with DM was 26.87%. In the DM group, there was a higher incidence of hypertension and Candida spp. infection. Conservative administration and percutaneous drainage were mainly used in patients with good- (60.87%) and poor-control (60.53%) of glycaemia, respectively. During follow-up, 24 (10.57%) died due to uncontrolled systemic infections and other serious complications. Compared with PLA patients without DM, patients in the DM group had significantly increased 6-month mortality rate after discharge (Log-Rank test, P = 0.021). Poor-control of glycaemia did not reduce the six-month survival, while the recurrence rate of PLA within 3 months showed an almost 3-fold increase (13.16% vs. 4.35%). Further multivariate analyses found that DM was the only independent risk factor for the PLA six-month survival (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.138-8.010, P = 0.026). However, the blood glucose level had no significant effect on the short-term survival of PLA patients with DM (Log-Rank test, P = 0.218). CONCLUSIONS: In PLA patients, DM aggravated short-term mortality and blood glucose levels should be well controlled.


Assuntos
Complicações do Diabetes/complicações , Complicações do Diabetes/epidemiologia , Abscesso Hepático Piogênico/complicações , Abscesso Hepático Piogênico/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia , Criança , Complicações do Diabetes/mortalidade , Feminino , Hospitalização , Humanos , Abscesso Hepático Piogênico/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
20.
Stroke ; 49(12): 3060-3062, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30571412

RESUMO

Background and Purpose- Clot migration to distal intracranial arterial segments was observed in patients presented with acute large vessel occlusions. It is postulated that the exposure of patients to intravenous thrombolysis (IVT) increases the risk of clot migration and associated with inaccessibility of the clot by endovascular thrombectomy (EVT). In this study, we aimed to investigate the incidence of clot migration and its association with IVT before EVT. Methods- We conducted a single-center retrospective analysis of patients who had EVT during the period 2009 to 2016. Patients who fulfilled clinical criteria were treated with bridging IVT and those who did not were treated with direct EVT. Clot position was assessed by pretreatment computed tomography angiogram or magnetic resonance angiogram and was compared with clot position identified by digital subtraction angiography before planned endovascular thrombectomy. Results- Of 314 included patients, clot migration occurred in 43 patients (13.7%). The proportion of clot migration was 18.7% (39 of 209) in patients who had bridging IVT with EVT compared with 3.8% (4 of 105) in direct EVT ( P=0.001). Of the 39 patients who had clot migration in the bridging IVT with EVT, 59.0% (23 of 39) demonstrated clot inaccessibility compared with 25.0% (1 of 4) in clot migration cases in the direct EVT group ( P=0.011). Conclusions- The incidence of clot migration was significantly increased in the setting of bridging IVT before EVT, leading to increased proportion of clot inaccessibility by EVT.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Administração Intravenosa , Idoso , Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares , Feminino , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombectomia , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa