RESUMO
Endothelial dysfunction and impaired vasodilation are linked with adverse cardiovascular events. T lymphocytes expressing choline acetyltransferase (ChAT), the enzyme catalyzing biosynthesis of the vasorelaxant acetylcholine (ACh), regulate vasodilation and are integral to the cholinergic antiinflammatory pathway in an inflammatory reflex in mice. Here, we found that human T cell ChAT mRNA expression was induced by T cell activation involving the PI3K signaling cascade. Mechanistically, we identified that ChAT mRNA expression was induced following the attenuation of RE-1 Silencing Transcription factor REST-mediated methylation of the ChAT promoter, and that ChAT mRNA expression levels were up-regulated by GATA3 in human T cells. In functional experiments, T cell-derived ACh increased endothelial nitric oxide-synthase activity, promoted vasorelaxation, and reduced vascular endothelial activation and promoted barrier integrity by a cholinergic mechanism. Further, we observed that survival in a cohort of patients with severe circulatory failure correlated with their relative frequency of ChAT +CD4+ T cells in blood. These findings on ChAT+ human T cells provide a mechanism for cholinergic immune regulation of vascular endothelial function in human inflammation.
Assuntos
Colina O-Acetiltransferase , Linfócitos T , Humanos , Camundongos , Animais , Linfócitos T/metabolismo , Colina O-Acetiltransferase/genética , Colina O-Acetiltransferase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Colinérgicos , Acetilcolina/metabolismo , RNA Mensageiro/metabolismoRESUMO
Beige adipocytes have a discrete developmental origin and possess notable plasticity in their thermogenic capacity in response to various environmental cues, but the transcriptional machinery controlling beige adipocyte development and thermogenesis remains largely unknown. By analyzing beige adipocyte-specific knockout mice, we identified a transcription factor, forkhead box P4 (FOXP4), that differentially governs beige adipocyte differentiation and activation. Depletion of Foxp4 in progenitor cells impaired beige cell early differentiation. However, we observed that ablation of Foxp4 in differentiated adipocytes profoundly potentiated their thermogenesis capacity upon cold exposure. Of note, the outcome of Foxp4 deficiency on UCP1-mediated thermogenesis was confined to beige adipocytes, rather than to brown adipocytes. Taken together, we suggest that FOXP4 primes beige adipocyte early differentiation, but attenuates their activation by potent transcriptional repression of the thermogenic program.
Assuntos
Adipócitos Bege , Adipócitos Marrons , Animais , Diferenciação Celular/genética , Regulação da Expressão Gênica , Camundongos , Termogênese/genéticaRESUMO
PURPOSE: Extracorporeal cardiopulmonary resuscitation (ECPR) might markedly increase the survival of selected patients with refractory cardiac arrest. But the application situation and indications remained unclear. MATERIALS AND METHODS: We respectively reviwed all adult patients who underwent ECPR from January 2017 to March 2021. Patient characteristics, initiation and management of ECMO, complications, and outcomes were collected and compared between the survivors and nonsurvivors. LASSO regression was used to screen risk factors. Multivariate logistic regression was performed with several parameters screened by LASSO regression. RESULTS: Data were reported from 42 ECMO centers covering 19 provinces of China. A total of 648 patients were included in the study, including 491 (75.8%) males. There were 11 ECPR centers in 2017, and the number increased to 42 in 2020. The number of patients received ECPR increased from 33 in 2017 to 274 in 2020, and the survival rate increased from 24.2% to 33.6%. Neurological complications, renal replacement therapy, epinephrine dosage after ECMO, recovery of spontaneous circulation before ECMO, lactate clearance and shockable rhythm were risk factors independently associated with outcomes of whole process. Sex, recovery of spontaneous circulation before ECMO, lactate, shockable rhythm and causes of arrest were pre-ECMO risk factors independently affecting outcomes. CONCLUSIONS: From January 2017 to March 2021, the numbers of ECPR centers and cases in mainland China increased gradually over time, as well as the survival rate. Pre-ECMO risk factors, especially recovery of spontaneous circulation before ECMO, shockable rhythm and lactate, are as important as post-ECMO management,. Neurological complications are vital risk factors after ECMO that deserved close attention. TRIAL REGISTRATION: NCT04158479, registered on 2019/11/08. https://clinicaltrials.gov/NCT04158479.
Assuntos
Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Humanos , Masculino , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , China/epidemiologia , Feminino , Estudos Retrospectivos , Reanimação Cardiopulmonar/métodos , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Parada Cardíaca/terapia , Parada Cardíaca/epidemiologia , Parada Cardíaca/mortalidade , Taxa de Sobrevida , IdosoRESUMO
Evidence displays that circular RNAs (circRNAs) are considerable mediators of numerous processes in cancer development. Given that many circRNAs are not functionally characterized, our aim was to explore the function and mechanisms of circ_0051428 in thyroid cancer (TC). The analysis of circ_0051428, miR-1248 and FN1 mRNA expression was conducted using real-time quantitative polymerase chain reaction. Cell growth was observed using CCK-8 and colony formation assays. Cell migration was investigated using wound healing assay. Cell apoptosis was identified by the expression of apoptosis-related proteins (Bax and Bcl-2) using Western blotting. Animal models were established to testify the role of circ_0051428 in vivo. The assumed binding between miR-1248 and circ_0051428 or FN1 was identified using dual-luciferase reporter or RIP assay. circ_0051428 exhibits an abnormally elevated expression in TC. circ_0051428 deficiency caused inhibition of TC cell proliferation, migration, clonogenic capacity, and inhibition of tumor growth in vivo. circ_0051428 directly targeted miR-1248, and FN1 was a target downstream of circ_0051428/miR-1248 axis. circ_0051428 could sponge miR-1248 to upregulate FN1. Furthermore, miR-1248 downregulation recovered circ_0051428 deficiency-suppressed cancer cell proliferation, survival and migration. Besides, the repressive effects of FN1 knockdown on cancer cell growth, survival and migration were also partly abolished by miR-1248 downregulation. circ_0051428 targeted miR-1248 to modulate FN1 expression, thereby facilitating the malignant progression of TC, which contributed to the understanding of the molecular mechanism of TC development.
Assuntos
MicroRNAs , Neoplasias da Glândula Tireoide , Animais , RNA Circular/genética , Neoplasias da Glândula Tireoide/genética , Apoptose/genética , Western Blotting , Proliferação de Células/genética , MicroRNAs/genética , Linhagem Celular TumoralRESUMO
Preclinical studies indicate that (2R,6R)-hydroxynorketamine (HNK) is a putative fast-acting antidepressant candidate. Although inhibition of NMDA-type glutamate receptors (NMDARs) is one mechanism proposed to underlie ketamine's antidepressant and adverse effects, the potency of (2R,6R)-HNK to inhibit NMDARs has not been established. We used a multidisciplinary approach to determine the effects of (2R,6R)-HNK on NMDAR function. Antidepressant-relevant behavioral responses and (2R,6R)-HNK levels in the extracellular compartment of the hippocampus were measured following systemic (2R,6R)-HNK administration in mice. The effects of ketamine, (2R,6R)-HNK, and, in some cases, the (2S,6S)-HNK stereoisomer were evaluated on the following: (i) NMDA-induced lethality in mice, (ii) NMDAR-mediated field excitatory postsynaptic potentials (fEPSPs) in the CA1 field of mouse hippocampal slices, (iii) NMDAR-mediated miniature excitatory postsynaptic currents (mEPSCs) and NMDA-evoked currents in CA1 pyramidal neurons of rat hippocampal slices, and (iv) recombinant NMDARs expressed in Xenopus oocytes. While a single i.p. injection of 10 mg/kg (2R,6R)-HNK exerted antidepressant-related behavioral and cellular responses in mice, the ED50 of (2R,6R)-HNK to prevent NMDA-induced lethality was found to be 228 mg/kg, compared with 6.4 mg/kg for ketamine. The 10 mg/kg (2R,6R)-HNK dose generated maximal hippocampal extracellular concentrations of â¼8 µM, which were well below concentrations required to inhibit synaptic and extrasynaptic NMDARs in vitro. (2S,6S)-HNK was more potent than (2R,6R)-HNK, but less potent than ketamine at inhibiting NMDARs. These data demonstrate the stereoselectivity of NMDAR inhibition by (2R,6R;2S,6S)-HNK and support the conclusion that direct NMDAR inhibition does not contribute to antidepressant-relevant effects of (2R,6R)-HNK.
Assuntos
Antidepressivos/farmacologia , Ketamina/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Concentração Inibidora 50 , Ketamina/administração & dosagem , Ketamina/química , Masculino , Camundongos , N-Metilaspartato/metabolismo , Subunidades Proteicas/metabolismo , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Ratos , Xenopus laevisRESUMO
Leaf size is an important agronomic trait directly affecting yield in rice, and thus understanding the genes determining leaf size is important in breeding. In this study, one Leaf Mutant 7 (lm7) with small leaf size was isolated using ethyl methane sulphonate (EMS) mutagenesis from the japonica Zhenggeng 1925. MutMap by whole genome resequencing of phenotypic bulks revealed that LM7 is likely located in the 133 kb region on chromosome 7 using F2 population from a cross between lm7 and wild-type (WT) Zhenggeng 1925. The candidate gene encoding heat shock protein OsHSP40 for LM7 was functionally validated. Disruption of this gene in Oshsp40 mutants significantly reduced the leaf size compared with that of WT in rice. Microscopic examination showed that OsHSP40 modulated leaf size via regulating the veins formation and cell size/cell number. Nucleotide diversity analysis indicated that a single nucleotide polymorphism (SNP) variation of C to T in the coding region of OsHSP40 may cause small leaves among rice accessions. Therefore, the natural variation of OsHSP40 contributing to leaf size might be useful for rice breeding.
Assuntos
Oryza , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Oryza/genética , Oryza/metabolismo , Fenótipo , Melhoramento Vegetal , Folhas de Planta/genética , Folhas de Planta/metabolismo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Neuregulin-1 (NRG-1) is reported to be cardioprotective through the extracellular-regulated protein kinase (ERK) 1/2 pathway in myocardial ischaemia-reperfusion injury (MIRI). NOX4-induced ROS activated NLRP3 inflammasome and exacerbates MIRI. This study aims to investigate whether NRG-1 can suppress NOX4 by ERK1/2 and consequently inhibit the NLRP3/caspase-1 signal in MIRI. The myocardial infarct size (IS) was measured by TTC-Evans blue staining. Immunohistochemical staining, real-time quantitative PCR (RT-qPCR) and Western blotting were used for detection of the factors, such as NOX4, ERK1/2, NLRP3, caspase-1 and IL-1ß .The IS in the NRG-1 (3 µg/kg, intravenous) group was lower than that in the IR group. Immunohistochemical analysis revealed NRG-1 decreased 4HNE and NOX4. The RT-qPCR and Western blot analyses revealed that NRG-1 mitigated the IR-induced up-regulation of NOX4 and ROS production. Compared with the IR group, the NRG-1 group exhibited a higher level of P-ERK1/2 and a lower level of NLRP3. In the Langendorff model, PD98059 inhibited ERK1/2 and up-regulated the expression of NOX4, NLRP3, caspase-1 and IL-1ß, which exacerbated oxidative stress and inflammation. In conclusion, NRG-1 can reduce ROS production by inhibiting NOX4 through ERK1/2 and inhibit the NLRP3/caspase-1 pathway to attenuate myocardial oxidative damage and inflammation in MIRI.
Assuntos
Caspase 1/metabolismo , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/metabolismo , NADPH Oxidase 4/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuregulina-1/metabolismo , Estresse Oxidativo , Animais , Biomarcadores , Biópsia , Modelos Animais de Doenças , Expressão Gênica , Imuno-Histoquímica , Masculino , Modelos Biológicos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Neuregulina-1/genética , RatosRESUMO
Fundamental human traits, such as language and bipedalism, are associated with a range of anatomical adaptations in craniofacial shaping and skeletal remodeling. However, it is unclear how such morphological features arose during hominin evolution. FOXP2 is a brain-expressed transcription factor implicated in a rare disorder involving speech apraxia and language impairments. Analysis of its evolutionary history suggests that this gene may have contributed to the emergence of proficient spoken language. In the present study, through analyses of skeleton-specific knockout mice, we identified roles of Foxp2 in skull shaping and bone remodeling. Selective ablation of Foxp2 in cartilage disrupted pup vocalizations in a similar way to that of global Foxp2 mutants, which may be due to pleiotropic effects on craniofacial morphogenesis. Our findings also indicate that Foxp2 helps to regulate strength and length of hind limbs and maintenance of joint cartilage and intervertebral discs, which are all anatomical features that are susceptible to adaptations for bipedal locomotion. In light of the known roles of Foxp2 in brain circuits that are important for motor skills and spoken language, we suggest that this gene may have been well placed to contribute to coevolution of neural and anatomical adaptations related to speech and bipedal locomotion.
Assuntos
Remodelação Óssea/genética , Fatores de Transcrição Forkhead , Locomoção/genética , Mutação , Proteínas Repressoras , Crânio/metabolismo , Vocalização Animal , Animais , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Membro Posterior/metabolismo , Humanos , Camundongos , Camundongos Knockout , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
BACKGROUND: Most countries set regulatory values for the total trace element (TE) concentrations in soil, although there is growing interest in using a risk-based approach to evaluate the bioavailable TE using dilute salt extractants or other soil parameters, including pH and organic carbon. The present study compares the current regulatory system (based on total TEs and pH) and a risk-based approach using 0.01 mol L-1 CaCl2 to estimate the bioavailable fraction. RESULTS: In total, 150 paired samples of Chinese flowering cabbages (Brassica parachinensis) and their growth soils were collected, and the total and extractable concentrations of chromium (Cr), cadmium (Cd), lead (Pb), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As) and mercury (Hg), as well as soil pH and organic matter content, were measured. No more than 3.33% of the edible parts exceeded Chinese food safety standards, even when growing in soils exceeding the current regulatory thresholds by over 50%. The total soil Cd (1.5 mg kg-1 ), as well as the extractable concentrations of Cd (0.1 mg kg-1 ), Ni (0.03 mg kg-1 ) and Zn (0.1 mg kg-1 ), are the key factors affecting the TE concentrations in B. parachinensis. CONCLUSION: Our findings suggest that the current soil regulatory guidelines for safe production of B. parachinensis are overly strict and conservative. A risk-based approach based on the extractable TE concentrations would provide a better indication for plant uptake of soil TEs and avoid the waste of farmlands that can still produce safe vegetables. Future research should focus on providing crop-specific available TE concentration guidelines to promote effective utilization of farmlands. © 2021 Society of Chemical Industry.
Assuntos
Brassica/química , Oligoelementos/análise , Arsênio/análise , Brassica/classificação , Brassica/crescimento & desenvolvimento , Cádmio/análise , China , Cromo/análise , Cobre/análise , Inocuidade dos Alimentos , Mercúrio/análise , Metais Pesados/análise , Níquel/análise , Solo/química , Poluentes do Solo/análise , Verduras/química , Verduras/classificação , Verduras/crescimento & desenvolvimento , Zinco/análiseRESUMO
Nitrogen (N) forms not only affect cadmium (Cd) accumulation in plants, but also affect plant resistance to Cd toxicity. However, few researches have been reported underlying the mechanism of the relationship between nitrogen forms and plant resistance under Cd exposure. Here, we explored the mechanism on how different NO3-/NH4+ ratios affect antioxidase system and the glutathione-ascorbate cycle under five different ratios of NO3-/NH4+ (1:0, 2:1, 1:1, 1:2, 0:1) and three dosages of Cd exposure (0, 1, 5 µmol L-1 Cd) in rice (Oryza sativa L.). The results showed that high NO3- and high Cd exposure both significantly inhibited tissue growth of rice plants, and this inhibiting trend was mitigated with increasing NH4+ ratios as proved by the increased biomass and the decreased concentrations of malonaldehyde (MDA) and hydrogen peroxide (H2O2), as well as the levels of Cd contents in rice tissues. Additionally, high NH4+ ratios elevated the SOD activities in rice tissues, especially at high Cd treatment. However, other two antioxidases (CAT and APX) were insensitive to changes of NO3-/NH4+ ratios (except the full NO3-). Furthermore, high NH4+ ratios induced increasing of the efficiency of glutathione-ascorbate cycle (GSH-AsA) under two levels of Cd exposure, as evidenced by increasing concentrations of GSH and AsA and the activities of GR and DHAR in rice tissues. Overall, these results revealed that ammonium nutrition caused an enhancement resistance to Cd stress in rice plants was responsible for increasing of partial antioxidase system and the efficiencies of GSH-AsA cycle.
Assuntos
Compostos de Amônio/farmacologia , Ácido Ascórbico/metabolismo , Cádmio/toxicidade , Glutationa/metabolismo , Oryza/metabolismo , Compostos de Amônio/análise , Cádmio/metabolismo , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Nitratos/análise , Nitratos/farmacologia , Oryza/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismoRESUMO
Antimony (Sb) excess accumulation in edible parts of crops causes potential risks to human health. However, knowledge about the mechanisms of its accumulation within vegetable plants is still not well known. Here, we investigated the physiological processes of Sb involved in symplastic and apoplastic absorption, compartmentation by roots, and translocation in xylem in Brassica parachinensis L. exposed to antimonate (SbV) and antimonite (SbIII) forms. The results showed that plants treated with SbIII emerged to be more toxic than SbV as proved by the lower biomass and the higher concentrations of malonaldehyde (MDA) and hydrogen peroxide (H2O2) in plant tissues, especially at high dosages. The Sb concentration showed more in shoots but less in roots treated with SbV than with SbIII. The total Sb accumulation was higher under the SbV treatment than the SbIII treatment, mainly due to the higher accumulation in shoots. Additionally, the Sb concentration in symplastic flow of roots was higher exposed to SbV than SbIII, while no differences were found for the Sb concentration in apoplastic flow between them. Moreover, the Sb concentration in cell walls of roots was higher exposed to SbIII than SbV, especially at high levels. Furthermore, the Sb concentration in xylem was higher exposed to SbV than SbIII, and a greatly positive correlation was observed between the Sb concentrations in xylem and shoots. Overall, these findings revealed that vegetable plants accumulated more SbV than SbIII in edible parts mainly due to xylem translocation rather than root absorption.
Assuntos
Antimônio/farmacocinética , Brassica/metabolismo , Absorção Fisiológica , Antimônio/toxicidade , Transporte Biológico , Brassica/efeitos dos fármacos , Parede Celular/metabolismo , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Raízes de Plantas/metabolismo , Xilema/metabolismoRESUMO
BACKGROUND: This study aimed to investigate the image quality and adverse events (AEs) of ethiodized poppyseed oil (EPO) compared with ioversol as contrast agents in hysterosalpingography (HSG). METHODS: Two hundred twenty-eight patients underwent HSG were consecutively recruited in this prospective cohort study, and were accordingly divided into EPO group (N = 165) and ioversol group (N = 63). The quality of image was assessed according to the European Guidelines on quality criteria for diagnostic radiographic images. AEs during, within 2 h and at 1-month post-HSG were recorded. RESULTS: EPO displayed elevated image quality compared with ioversol including the total image quality score (P < 0.001), the cervical canal display score (P < 0.001), shape and outline of uterus score (P < 0.01), cervical mucosa or folds score (P < 0.001), oviduct isthmus score (P < 0.001), ampulla and fimbriae of oviduct score (P < 0.001) and celiac diffuse image score (P < 0.001). Multivariate linear regression displayed that EPO (P < 0.001) was an independent predictive factor for increased total image quality score. AEs were similar between EPO group and ioversol group during and within 2 h post-HSG (all P > 0.05). However, at 1-month post-HSG, the number of patients had unchanged and faded menstrual blood color decreased but the proportion of patients with deepened menstrual color increased in EPO group compared with ioversol group (P = 0.007). In addition, the number of patients had iodine residue in uterine cavity was elevated in EPO group compared with ioversol group (P < 0.001). CONCLUSION: EPO is more efficient in image quality and equally tolerant compared to ioversol as contrast agents in HSG.
Assuntos
Óleo Etiodado/administração & dosagem , Doenças dos Genitais Femininos/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Ácidos Tri-Iodobenzoicos/administração & dosagem , Adulto , Meios de Contraste/administração & dosagem , Meios de Contraste/efeitos adversos , Óleo Etiodado/efeitos adversos , Feminino , Humanos , Histerossalpingografia/métodos , Infertilidade Feminina/diagnóstico por imagem , Modelos Lineares , Pessoa de Meia-Idade , Estudos Prospectivos , Ácidos Tri-Iodobenzoicos/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: To investigate the status and influencing factors of the knowledge and behavior related to brucellosis among occupational workers in Jianyang city, and to provide basic information for developing regional specific strategies for brucellosis prevention and control. METHODS: With multistage cluster random sampling, occupational workers aged ≥18 yr. who had been in contact with sheep and their products were interviewed through a questionnaire about demographic characteristic, knowledge, and behavior related to brucellosis. The knowledge and practice scores were described as frequency and percentage, and the awareness rate of knowledge about brucellosis was calculated. Unconditional logistic regression model was used to analyze the influencing factors of knowledge and behavior related to brucellosis. RESULTS: In total, 378 workers were recruited. The minority (25.1%) of the workers had heard of brucellosis, and the awareness rate of brucellosis was 22.0%. Occupational protective behaviors were poor, and the scoring rates of wearing protective clothes, mask and gloves were 58.7%, 76.5%, 71.7% respectively. The results of multivariate logistic regression analysis revealed that the awareness rate of knowledge about brucellosis decreased with age, while the low educational level was found to be associated with low awareness of knowledge about brucellosis, and occupation type had association with the awareness rate of knowledge. Besides, the awareness of knowledge about brucellosis was a protective factor and occupation type were associated with the behavior related to brucellosis. CONCLUSIONS: The knowledge and behavior related to brucellosis are poor among occupational workers in Jianyang. It is necessary to continuously implement targeted health education and health promotion programs in this region, and the people with low education level and livestock farmers should be paid special attention to.
Assuntos
Brucelose , Conhecimentos, Atitudes e Prática em Saúde , Exposição Ocupacional/prevenção & controle , Animais , Humanos , Modelos Logísticos , Ovinos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The protective effect of Neuregulin-1 (NRG-1) on heart failure is well established. In this study, we assessed whether NRG-1 could protect the heart by mimicking the cardioprotective effects of ischaemic postconditioning (IP). METHODS: We used a myocardial reperfusion injury rat model in vivo to compare the cardioprotective effects of NRG-1(3 µg/kg, iv. at the onset of reperfusion) and IP. In Langendorff isolated heart perfusion experiments, we used the erythroblastic leukaemia viral oncogene homolog 4 (ErbB4) inhibitor AG1478, a phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and a mitogen-activated protein/extracellular signal regulated kinase (MEK) inhibitor PD98059 to clarify whether the protective effects of NRG-1and IP depend on the NRG-1/ErbB4 signals and the reperfusion injury salvage kinase (RISK) pathway. Infarct size was detected by Evans blue and TTC. Apoptosis was detected by TUNEL assays. The expression of NRG-1/ErbB4 and downstream ERK1/2, AKT, AMPK and p70s6K were detected by western blotting. Hematoxylin/eosin (H&E) staining was used for histological analysis. RESULTS: We found that NRG-1 and IP had similar effects on reducing myocardial infarct size and apoptosis in vivo. NRG-1 heart protein levels were upregulated in the IP group. Phosphorylation of AKT, ERK1/2 and ErbB4 were also increased in both the IP and NRG-1 groups. Furthermore, in Langendorff analyses, the ErbB4 inhibitor AG1478 suppressed the phosphorylation of ErbB4 and the RISK pathway and aggravated myocardial edema and fiber fracture, thereby inhibited the cardioprotective effects in both the IP and NRG-1 groups. For assessment of downstream signals, the PI3K inhibitor LY294002 and the MEK inhibitor PD98059 suppressed the phosphorylation of AKT and ERK1/2 respectively and abolished the cardioprotective effects induced by IP and NRG-1. CONCLUSION: In conclusion, both IP and NRG-1 could reduce infarct size and apoptosis through ErbB4-dependent activation of the RISK pathway in the same model; these results indicated the therapeutic potential of NRG-1 as a pharmacological postconditioning agent against myocardial reperfusion injury.
Assuntos
Cardiotônicos/farmacologia , Pós-Condicionamento Isquêmico , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Neuregulina-1/farmacologia , Receptor ErbB-4/metabolismo , Animais , Apoptose/efeitos dos fármacos , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Infarto do Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
Silicon (Si) and selenium (Se) are beneficial for many higher plants when grown on stress conditions. However, the mechanisms underlying the differential effects between foliar Si and Se in alleviation of plant toxicity exposed to cadmium (Cd) stress are remained unclear. In this study, we investigated the discrepant mechanisms of foliar Si and Se on Cd absorption and compartmentation by roots, its translocation in xylem, and the antioxidant system within Chinese flowering cabbage (Brassica campestris L. ssp. chinensis var. utilis) under low and high Cd stress. Results showed that plant growth was significantly enhanced by foliar additions of Si or/and Se according to an increased plant tissue biomass at high Cd exposure. In addition, the foliar coupled addition of Si and Se showed little effects on the concentrations of Si or Se in plant tissues in comparison with the single addition of foliar Si or Se respectively. The foliar Si alone or combined with Se markedly reduced the Cd concentrations in plant shoots under two Cd treatments. This might be explained by the lower Cd concentrations in symplast and apoplast and the higher Cd concentrations in cell walls of plant roots, and the lower Cd concentrations in xylem sap. However, no great changes in these values were observed under the treatments of foliar Se alone. Moreover, the foliar additions of Si or/and Se all increased the antioxidant enzyme activities of SOD, CAT and APX in plant tissues, especially at high Cd dosage. No significant differences in the increasing degrees of these three antioxidant enzymes were found between the foliar Si and Se treatments. However, only the foliar Se alone or combined with Si markedly promoted the antioxidant enzyme activities of GR and DHAR in plant tissues. Our findings demonstrate that the alleviation of Cd toxicity by foliar Si maybe mainly responsible for inhibition of Cd absorption and its translocation to plant shoots, reinforcing its compartmentation into root cell walls, whilst enhancing the antioxidant enzyme system may be employed by foliar Se.
Assuntos
Brassica/metabolismo , Cádmio/farmacocinética , Selênio/farmacologia , Silício/farmacologia , Absorção Fisiológica , Antioxidantes/metabolismo , Transporte Biológico , Biomassa , Brassica/enzimologia , Brassica/crescimento & desenvolvimento , Parede Celular/metabolismo , Brotos de Planta/metabolismo , Xilema/metabolismoRESUMO
Organoarsenic arsanilic acid (ASA) contamination of paddy soil is a serious but less concerned hazard to agriculture and health of people consuming rice as staple food, for rice is one major pathway of arsenic (As) exposure to human food. To date little research has studied the effect of ASA on biochemical process of rice. Silicon (Si) application is able to reduce the toxicities of heavy metals in numerous plants, but little information about ASA. This work investigated whether and how Si influenced alleviation of ASA toxicity in rice at biochemical level to have a better understanding of defense mechanism by Si against ASA stress. Results showed that ASA reduced rice growth, disturbed protein metabolism, increased lipid peroxidation but decreased the efficiencies of antioxidant activities compared to control plants, more severe in roots than in shoots. The addition of Si in ASA-stressed rice plants noticeably increased growth and development as well as soluble protein contents, but decreased malondialdehyde (MDA) contents in ASA-stressed rice plants, suggesting that Si did have critical roles in ASA detoxification in rice. Furthermore, increased superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities along with elevated glutathione (GSH) and ascorbic acid (AsA) contents implied the active involvement of ROS scavenging and played, at least in part, to Si-mediated alleviation of ASA toxicity in rice, and these changes were related to rice genotypes and tissues. The study provided physio-chemical mechanistic evidence on the beneficial effect of Si on organoarsenic ASA toxicity in rice seedlings.
Assuntos
Ácido Arsanílico/toxicidade , Oryza/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Plântula/efeitos dos fármacos , Silício/farmacologia , Antioxidantes/farmacologia , Ácido Ascórbico/metabolismo , Catalase/metabolismo , Fenômenos Químicos , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Oryza/metabolismo , Peroxidase , Raízes de Plantas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Plântula/metabolismo , Solo/química , Superóxido Dismutase/metabolismoRESUMO
P-arsanilic acid (AsA) is a emerging but less concerned contaminant used in animal feeding operations, for it can be degraded to more toxic metabolites after being excreted by animals. Rice is the staple food in many parts of the world, and also more efficient in accumulating arsenic (As) compared to other cereals. However, the uptake and transformation of AsA by rice is unclear. This study aimed to evaluate the potential risk of using AsA as a feed additive and using the AsA contaminated animal manure as a fertilizer. Five rice cultivars were grown in soil containing 100mg AsA/kg soil, after harvest, As species and their concentrations in different tissues were determined. Total As concentration of the hybrid rice cultivar was more than conventional rice cultivars for whole rice plant. For rice organs, the highest As concentration was found in roots. AsA could be absorbed by rice, partly degraded and converted to arsenite, monomethylarsonic acid, dimethylarsinic acid, arsenate. The number of As species and their concentrations in each cultivar were related to their genotypes. The soil containing 100mg AsA/kg or more is unsuitable for growing rice. The use of AsA and the disposal of animal manure requires detailed attention.
Assuntos
Arsênio/metabolismo , Oryza/metabolismo , Ração Animal/análise , Animais , Ácido Arsanílico/metabolismo , Ácido Arsanílico/toxicidade , Arseniatos/metabolismo , Arsênio/análise , Arsenicais/metabolismo , Arsenitos/metabolismo , Arsenitos/toxicidade , Ácido Cacodílico/metabolismo , Fertilizantes/análise , Contaminação de Alimentos/análise , Esterco/análise , Raízes de Plantas/metabolismo , Solo/química , Poluentes do Solo/toxicidadeRESUMO
BACKGROUND: Corneal perforation in severe Stevens-Johnson syndrome (SJS) presenting great therapeutic difficulties, the imperative corneal transplantation always result in graft failure and repeated recurrence of perforation. The aim of this study was to evaluate the effectiveness of a modified small tectonic keratoplasty (MSTK) with minimal corneal graft in the management of refractory corneal perforation in severe SJS. METHODS: Refractory corneal perforations in ten patients (10 eyes) with severe SJS were mended with a minimal corneal patch graft, under the guidance of anterior chamber optical coherence tomography, combined with conjunctival flap covering. The outcome measures included healing of the corneal perforation, survival of the corneal graft and conjunctival flap, relevant complications, and improvement in visual acuity. RESULTS: Corneal perforation healed, and global integrity was achieved in all eyes. No immune rejection or graft melting was detected. Retraction of conjunctival flap occurred in one eye, which was treated with additional procedure. Visual acuity improved in six eyes (60%), unchanged in three eyes (30%) and declined in one eye (10%). CONCLUSIONS: The MSTK combined with conjunctival flap covering seems to be effective for refractory corneal perforation in severe SJS.
Assuntos
Perfuração da Córnea/cirurgia , Ceratoplastia Penetrante/métodos , Síndrome de Stevens-Johnson/complicações , Retalhos Cirúrgicos , Adulto , Idoso , Câmara Anterior/patologia , Túnica Conjuntiva/transplante , Perfuração da Córnea/diagnóstico , Perfuração da Córnea/etiologia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Stevens-Johnson/diagnóstico , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual , Adulto JovemRESUMO
Microangiogenesis is an important prognostic factor in various cancers, including hepatocellular carcinoma (HCC). The Vascular Endothelial Growth Factor (VEGF) has been shown to contribute to tumor angiogenesis. Recently, several studies have investigated the regulation of VEGF production by a single gene, with few researchers exploring all genes that affect VEGF production. In this study, we comprehensively analyzed all genes affecting VEGF production in HCC and developed a risk model and gene-based risk score based on VEGF production. Moreover, the model's predictive capacity on prognosis of HCCs was verified using training and validation datasets. The developed model showed good prediction of the overall survival rate. Patients with a higher risk score experienced poor outcomes compared to those with a lower risk score. Furthermore, we identified the immunological causes of the poor prognosis of patients with high-risk scores comparing with those with low-risk scores.