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1.
Mol Cell ; 82(20): 3810-3825.e8, 2022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-36108631

RESUMO

Human mixed-lineage leukemia (MLL) family methyltransferases methylate histone H3 lysine 4 to different methylation states (me1/me2/me3) with distinct functional outputs, but the mechanism underlying the different product specificities of MLL proteins remains unclear. Here, we develop methodologies to quantitatively measure the methylation rate difference between mono-, di-, and tri-methylation steps and demonstrate that MLL proteins possess distinct product specificities in the context of the minimum MLL-RBBP5-ASH2L complex. Comparative structural analyses of MLL complexes by X-ray crystal structures, fluorine-19 nuclear magnetic resonance, and molecular dynamics simulations reveal that the dynamics of two conserved tyrosine residues at the "F/Y (phenylalanine/tyrosine) switch" positions fine-tune the product specificity. The variation in the intramolecular interaction between SET-N and SET-C affects the F/Y switch dynamics, thus determining the product specificities of MLL proteins. These results indicate a modified F/Y switch rule applicable for most SET domain methyltransferases and implicate the functional divergence of MLL proteins.


Assuntos
Histona-Lisina N-Metiltransferase , Leucemia , Humanos , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Lisina/metabolismo , Flúor/metabolismo , Proteína de Leucina Linfoide-Mieloide/metabolismo , Tirosina , Fenilalanina
2.
Nature ; 576(7786): 301-305, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31801997

RESUMO

A central aspect of aging research concerns the question of when individuality in lifespan arises1. Here we show that a transient increase in reactive oxygen species (ROS), which occurs naturally during early development in a subpopulation of synchronized Caenorhabditis elegans, sets processes in motion that increase stress resistance, improve redox homeostasis and ultimately prolong lifespan in those animals. We find that these effects are linked to the global ROS-mediated decrease in developmental histone H3K4me3 levels. Studies in HeLa cells confirmed that global H3K4me3 levels are ROS-sensitive and that depletion of H3K4me3 levels increases stress resistance in mammalian cell cultures. In vitro studies identified SET1/MLL histone methyltransferases as redox sensitive units of the H3K4-trimethylating complex of proteins (COMPASS). Our findings implicate a link between early-life events, ROS-sensitive epigenetic marks, stress resistance and lifespan.


Assuntos
Longevidade , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Animais , Caenorhabditis elegans , Regulação para Baixo , Histonas/metabolismo , Larva
3.
Am J Emerg Med ; 80: 18-23, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479112

RESUMO

AIMS: To characterize the clinical features of ocular trauma resulting from lawn mower, identify determinants of unfavorable final visual acuity (FVA), and assess the spectrum of microbial in posttraumatic endophthalmitis. METHODS: This retrospective study enrolled patients who experienced ocular trauma due to lawn mower at Zhongshan Ophthalmic Center from January 2013 to August 2021. Demographics, clinical features, isolated microorganisms, risk factors influencing reduced visual acuity, treatment regimens, and utilization of eyewear were collected. RESULTS: The study included 140 participants (140 eyes) (49.47 ± 12.03 years, 95% male). The predominant injury manifestations were penetrating globe injuries (75.7%) and intraocular foreign bodies (51.4%). Endophthalmitis occurred in 35 cases (25%) and Bacillus cereus (23.5%) was the primary pathogen, followed by Staphylococcus epidermidis (11.8%) and Streptococcus species (11.8%). Following the initial assessment, where 77.9% of patients had initial visual acuity (IVA) at grade IV (ranging from light perception to 4/200) and only 0.7% attained grade I (better than 20/40), post-treatment results revealed that 5.7% achieved FVA at grade I, with a concurrent decrease in patients with grade IV vision to 64.3%. Multivariate logistic regression revealed that injury protection (p < 0.001, OR = 0.237, 95% CI = 0.126-0.446), IVA (p = 0.001, OR = 4.102, 95% CI = 1.730-9.729), and retinal detachment (p = 0.042, OR = 8.105, 95% CI = 1.075-61.111) were significant independent risk factors impacting FVA. CONCLUSION: Lawn mower often cause severe ocular injuries, with high-velocity metal foreign bodies that can lead to infections, most commonly caused by Bacillus cereus. Correct use of protective gear, initial vision assessment, and detecting retinal detachment are crucial for visual prognosis.


Assuntos
Endoftalmite , Acuidade Visual , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Endoftalmite/microbiologia , Endoftalmite/epidemiologia , Adulto , Corpos Estranhos no Olho/complicações , Corpos Estranhos no Olho/epidemiologia , Ferimentos Oculares Penetrantes/complicações , Ferimentos Oculares Penetrantes/epidemiologia , Traumatismos Oculares/epidemiologia , Traumatismos Oculares/complicações , Fatores de Risco , Idoso , China/epidemiologia
4.
Ophthalmic Res ; 67(1): 340-347, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38772353

RESUMO

INTRODUCTION: Weill-Marchesani syndrome (WMS) is a hereditary connective tissue disorder with substantial heterogeneity in clinical features and genetic etiology, so it is essential to define the full mutation spectrum for earlier diagnosis. In this study, we report Weill-Marchesani-like syndrome (WMS-like) change to autosomal dominance inheritance caused by novel haplotypic mutations in latent transforming growth factor beta-binding protein 2 (LTBP2). METHODS: Twenty-five members from a 4-generation Chinese family were recruited from Guangzhou, of whom nine were diagnosed with WMS-like disease, nine were healthy, and seven were of "uncertain" clinical status because of their young age. All members received detailed physical and ocular examinations. Whole-exome sequencing, Sanger sequencing, and real-time PCR were used to identify and verify the causative mutations in family members. RESULTS: Genetic sequencing revealed novel haplotypic mutations on the same LTBP2 chromosome associated with WMS-like, c. 2657C>A/p.T886K in exon 16 and deletion of exons 25-36. Real-time PCR and Sanger sequencing verified both mutations in patients with clinically diagnosed WMS-like, and in one "uncertain" child. In these patients, the haplotypic mutations led to ectopia lentis, short stature, and obesity. CONCLUSION: Our study revealed that WMS-like may be associated with haplotypic LTBP2 mutations with autosomal dominant inheritance.


Assuntos
Proteínas de Ligação a TGF-beta Latente , Mutação , Linhagem , Síndrome de Weill-Marchesani , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Análise Mutacional de DNA , População do Leste Asiático/genética , Sequenciamento do Exoma , Haplótipos , Proteínas de Ligação a TGF-beta Latente/genética , Reação em Cadeia da Polimerase em Tempo Real , Síndrome de Weill-Marchesani/genética , Síndrome de Weill-Marchesani/diagnóstico
5.
J Transl Med ; 21(1): 620, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700323

RESUMO

BACKGROUND: A significant proportion of septic patients with acute lung injury (ALI) are recognized late due to the absence of an efficient diagnostic test, leading to the postponed treatments and consequently higher mortality. Identifying diagnostic biomarkers may improve screening to identify septic patients at high risk of ALI earlier and provide the potential effective therapeutic drugs. Machine learning represents a powerful approach for making sense of complex gene expression data to find robust ALI diagnostic biomarkers. METHODS: The datasets were obtained from GEO and ArrayExpress databases. Following quality control and normalization, the datasets (GSE66890, GSE10474 and GSE32707) were merged as the training set, and four machine learning feature selection methods (Elastic net, SVM, random forest and XGBoost) were applied to construct the diagnostic model. The other datasets were considered as the validation sets. To further evaluate the performance and predictive value of diagnostic model, nomogram, Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) were constructed. Finally, the potential small molecular compounds interacting with selected features were explored from the CTD database. RESULTS: The results of GSEA showed that immune response and metabolism might play an important role in the pathogenesis of sepsis-induced ALI. Then, 52 genes were identified as putative biomarkers by consensus feature selection from all four methods. Among them, 5 genes (ARHGDIB, ALDH1A1, TACR3, TREM1 and PI3) were selected by all methods and used to predict ALI diagnosis with high accuracy. The external datasets (E-MTAB-5273 and E-MTAB-5274) demonstrated that the diagnostic model had great accuracy with AUC value of 0.725 and 0.833, respectively. In addition, the nomogram, DCA and CIC showed that the diagnostic model had great performance and predictive value. Finally, the small molecular compounds (Curcumin, Tretinoin, Acetaminophen, Estradiol and Dexamethasone) were screened as the potential therapeutic agents for sepsis-induced ALI. CONCLUSION: This consensus of multiple machine learning algorithms identified 5 genes that were able to distinguish ALI from septic patients. The diagnostic model could identify septic patients at high risk of ALI, and provide potential therapeutic targets for sepsis-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Sepse , Humanos , Consenso , Sepse/complicações , Acetaminofen , Lesão Pulmonar Aguda/diagnóstico , Lesão Pulmonar Aguda/etiologia , Aprendizado de Máquina , Inibidor beta de Dissociação do Nucleotídeo Guanina rho
6.
BMC Pulm Med ; 23(1): 435, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946194

RESUMO

BACKGROUND: Sepsis is a common cause of mortality in critically ill patients, and chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in septic patients. However, the impact of COPD on patients with sepsis remained unclear. Therefore, the purpose of this study aimed to assess the effect of COPD on the prognosis of septic patients based on Medical Information Mart for Intensive Care (MIMIC-III) database. METHODS: In this retrospective study based on the (MIMIC)-III database version 1.4 (v1.4), we collected clinical data and 28-day all-cause mortality from patients with sepsis in intensive care unit (ICU) and these patients met the diagnostic criteria of Sepsis 3 on ICU admission between 2008 and 2012. International Classification of Diseases (ICD-9) (4660, 490, 4910, 4911, 49120, 49121, 4918, 4919, 4920, 4928, 494, 4940, 4941, 496) was used to identified COPD. We applied Kaplan-Meier analysis to compare difference of 28-day all-cause mortality between septic patients with and without COPD. Cox proportional-hazards model was applied to explore the risk factor associated with 28-day all-cause mortality in patients with sepsis. RESULTS: Six thousand two hundred fifty seven patients with sepsis were included in this study, including 955 (15.3%) patients with COPD and 5302 patients without COPD (84.7%). Compared with patients without COPD, patients with COPD were older (median: 73.5 [64.4, 82.0] vs 65.8 [52.9, 79.1], P < 0.001), had higher simplified acute physiology score II (SAPSII) (median: 40.0 [33.0, 49.0] vs 38.0 [29.0,47.0], P < 0.001) and greater proportion of mechanical ventilatory support (MV) (55.0% vs 48.9%, P = 0.001). In our study, septic patients with COPD had higher 28-day all-cause mortality (23.6% vs 16.4%, P < 0.001) than patients without COPD. After adjusting for covariates, the results showed that COPD was an independent risk factor for the 28-day all-cause mortality of patients with sepsis (HR 1.30, 95%CI: 1.12-1.50, P = 0.001). CONCLUSIONS: COPD was an independent risk factor of 28-day all-cause mortality in septic patients. Clinically, septic patients with COPD should be given additional care.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Sepse , Humanos , Estudos Retrospectivos , Sepse/complicações , Unidades de Terapia Intensiva , Cuidados Críticos , Prognóstico
7.
J Biol Chem ; 296: 100635, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33823156

RESUMO

The methyltransferases MLL3 and MLL4 primarily catalyze the monomethylation of histone H3 lysine 4 (H3K4) on enhancers to regulate cell-type-specific gene expression and cell fate transition. MLL3 and MLL4 share almost identical binding partners and biochemical activities, but perform specific and nonredundant functions. The features and functions that distinguish MLL3 and MLL4 remain elusive. Here, we characterize the kinetic mechanisms of MLL3 and MLL4 ternary complexes containing the catalytic SET domain from MLL3 or MLL4 (MLL3SET or MLL4SET), the SPRY domain of ASH2L (ASH2LSPRY), and a short fragment of RBBP5 (RBBP5AS-ABM) to search for possible explanations. Steady-state kinetic analyses and inhibition studies reveal that the MLL3 complex catalyzes methylation in a random sequential bi-bi mechanism. In contrast, the MLL4 complex adopts an ordered sequential bi-bi mechanism, in which the cofactor S-adenosylmethionine (AdoMet) binds to the enzyme prior to the H3 peptide, and the methylated H3 peptide dissociates from the enzyme before S-adenosylhomocysteine (AdoHcy) detaches after methylation. Substrate-binding assays using fluorescence polarization (FP) confirm that AdoMet binding is a prerequisite for H3 binding for the MLL4 complex but not for the MLL3 complex. Molecular dynamic simulations reveal that the binding of AdoMet exclusively induces conformational constraints on the AdoMet-binding groove and the H3 substrate-binding pocket of MLL4, therefore stabilizing a specific active conformation to ease entry of the substrate H3. The distinct kinetic mechanisms and conformational plasticities provide important insights into the differential functions of MLL3 and MLL4 and may also guide the development of selective inhibitors targeting MLL3 or MLL4.


Assuntos
Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Histona-Lisina N-Metiltransferase/química , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Processamento de Proteína Pós-Traducional , Catálise , Proteínas de Ligação a DNA/genética , Histona-Lisina N-Metiltransferase/genética , Histonas/química , Humanos , Cinética , Metilação , Ligação Proteica
8.
BMC Infect Dis ; 22(1): 788, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36241980

RESUMO

BACKGROUND: Cytomegalovirus (CMV) has high seroprevalence, and its active infection is associated with several adverse prognoses in adult patients with acute respiratory distress syndrome (ARDS). However, the role of active CMV infection in ARDS-associated fibroproliferation is unknown. This study aimed at determining the association between active CMV infection and lung fibroproliferation in adult patients with ARDS. METHODS: We retrospectively reviewed the medical records of all adult patients with ARDS who were admitted to the intensive care unit (ICU) from January 2018 to December 2020 at a national university-affiliated hospital in China. Study subjects were divided into active and non-active CMV infection groups based on CMV DNAemia within a 28-day ICU hospitalization. Lung fibroproliferation was measured using chest high-resolution computed tomography (HRCT) and N-terminal peptide of serum procollagen III (NT-PCP-III) within the first 28 days of ICU admission. Pulmonary fibrosis, clinical features, laboratory findings, treatment measures, and clinical outcomes were compared between the two groups. RESULTS: Among the 87 ARDS patients included in this study, the incidence of active CMV infection was 16.1% within the 28-day ICU admission period. In logistic regression analyze, active CMV infection was found to be associated with higher pulmonary fibrogenesis, pulmonary fibrosis score, and NT-PCP-III level (P < 0.05). The duration of ICU stay in ARDS patients with active CMV infection was significantly higher than in those without active CMV infection (P < 0.05). CONCLUSIONS: Among adult patients with ARDS, active CMV infection was related to poor clinical outcomes. Active CMV infection was associated with ARDS-associated fibroproliferation. Prophylactic and preemptive use of anti-CMV agents on pulmonary fibrosis should be assessed to determine a consensus therapeutic strategy.


Assuntos
Infecções por Citomegalovirus , Fibrose Pulmonar , Síndrome do Desconforto Respiratório , Adulto , Citomegalovirus , Infecções por Citomegalovirus/complicações , Humanos , Unidades de Terapia Intensiva , Pulmão , Pró-Colágeno , Fibrose Pulmonar/etiologia , Estudos Retrospectivos , Estudos Soroepidemiológicos
9.
Int J Mol Sci ; 23(12)2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35743157

RESUMO

Traumatic optic neuropathy (TON) is a significant cause of vision loss and irreversible blindness worldwide. It is defined as retinal ganglion cell death and axon degeneration caused by injury. Optic nerve crush (ONC), a well-validated model of TON, activates retinal microglia and initiates neuroinflammation. High-mobility group box 1 (HMGB1), a non-histone chromosomal binding protein in the nucleus of eukaryotic cells, is an important inducer of microglial activation and pro-inflammatory cytokine release. The purpose of this study was to examine the protective effects and mechanism of the HMGB1 inhibitor BoxA to neuroinflammation-induced retinal ganglion cells (RGCs) damage in traumatic optic neuropathy. For that purpose, an optic nerve crush model was established in C57BL/6J mice at 10-12 weeks. Model mice received an intravitreal injection of PBS and the HMGB1 inhibitor BoxA. Our data demonstrated that HMGB1 expression increased after optic nerve crush. Retinal ganglion cell function and morphology were damaged, and retinal ganglion cell numbers were reduced after optic nerve crush. Intravitreal injection of BoxA after ONC can alleviate damage. Furthermore, BoxA reduced microglial activation and expression levels of nuclear factor κB (NF-kB), nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3), and apoptosis-associated speck-like protein containing a CARD (ASC) in experimental ONC mice. In summary, HMGB1 mediates NLRP3 inflammasome via NF-kB to participate in retinal inflammatory injury after ONC. Thus, intravitreal injection of BoxA has potential therapeutic benefits for the effective treatment of RGC death to prevent TON.


Assuntos
Proteína HMGB1 , Traumatismos do Nervo Óptico , Animais , Modelos Animais de Doenças , Proteína HMGB1/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Compressão Nervosa , Doenças Neuroinflamatórias , Traumatismos do Nervo Óptico/tratamento farmacológico , Traumatismos do Nervo Óptico/metabolismo , Células Ganglionares da Retina/metabolismo
10.
BMC Ophthalmol ; 19(1): 204, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31601186

RESUMO

BACKGROUND: The metabolic activity of retina is higher than other human tissues and is crucial to the vision. Cynomolgus macaques is widely used in ophthalmic disease research. The evaluation and comparison of macular and optic disc vascular circulation parameters between normal adult cynomolgus macaques and healthy adult humans using OCT-A can promote better use of nonhuman primate models in studies of ophthalmic vascular disease. METHODS: Twelve normal adult cynomolgus macaques with a mean age of 4.91 ± 0.43 years were studied for data collection. The macula of 28 adult healthy humans (14 males and 14 females), with a mean age of 25.11 ± 6.21 years and the optic discs of 9 adult healthy humans (4 males and 5 females) with a mean age of 28.56 ± 6.78 years were measured. The vessel density (VD) was measured using an RTVue XR with AngioVue. The scan sizes of the macular and optic discs were 3 × 3 mm and 4.5 × 4.5 mm, respectively. RESULTS: OCT-A can image the superficial and deep capillary plexuses and radial peripapillary capillary network. In RPC layer of the optic disc, the VD in the nasal quadrant was lower than the VD in the inferior temporal quadrant. Similarities and significant differences in VD between healthy humans and cynomolgus macaques were obtained using OCT-A. CONCLUSIONS: This study provides normal vascular parameters for adult cynomolgus macaques using OCT-A to help establish an optical parameter database for cynomolgus macaques and compare VD between healthy humans and cynomolgus macaques to promote choroid-retinopathy research. TRIAL REGISTRATION: Current Controlled Trials NCT03692169 , retrospectively registered on 26 sept 2018.


Assuntos
Angiofluoresceinografia/métodos , Disco Óptico/irrigação sanguínea , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto , Animais , Feminino , Fundo de Olho , Humanos , Macaca fascicularis , Masculino , Modelos Animais , Valores de Referência
11.
J Environ Manage ; 251: 109598, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563054

RESUMO

Antibiotic residues in soil may cause potential risks to human health and soil ecosystems. To avoid these potential risks, comprehensive study of the adsorption, transport and biodegradation of antibiotics in soil is very imperative. This review provided current views about the most recent studies, which have been conducted toward the adsorption, transport and biodegradation of antibiotics in soil. The influencing factors affecting the adsorption behaviors of antibiotics in soil, including the antibiotics properties (e.g., molecular structure, hydrophobicity, polarity, polarizability, and spatial configuration) and the soil characteristics (e.g., soil type, soil pH, coexisting ions, and soil organic matter), were discussed. The effects of fertilizer colloids, porous media, and pH of soil on the transport behaviors of antibiotics were analyzed. The biodegradation of antibiotics in soil were also highlighted by investigating the effects of soil microbiome, soil pH, soil temperature, and interactions between antibiotics. Prospects of antibiotics adsorption, transport and biodegradation were also proposed.


Assuntos
Poluentes do Solo , Solo , Adsorção , Antibacterianos , Ecossistema
12.
J Mater Sci Mater Med ; 29(11): 176, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30426241

RESUMO

Materials with low cell adhesion are advantageous for production of replacement intraocular lens (IOL) to prevent posterior capsular opacification (PCO). We evaluated the feasibility of compression molding for manufacture of silicone rubber with super-hydrophobic surface and low cell infiltrative characteristics compared to ordinary hydrophobic silicone rubber. Silicone specimens with complex surface topology (super-hydrophobic) or smooth surfaces (hydrophobic) were manufactured by vacuum deforming and molding. Contact angle, microscopic surface structure, and transparency were evaluated. Super-hydrophobic and smooth samples were compared for effects on proliferation, adhesion, and morphology of human lens epithelial cells (hLECs). Epithelial-mesenchymal transition (EMT) was examined by immunofluorescence expression of fibronectin (Fn), Alpha-smooth muscle actin (α-SMA), and vimentin. The surface contact angle of super-hydrophobic silicone was greater than that of smooth silicone (153.8° vs. 116°). The super-hydrophobic surface exhibited a micron-scale palisade structure under scanning electron microscopy (unit length, width, and height of 80, 25, and 25 µm, respectively). However, cell number per 50 × microscopic field on super-hydrophobic surfaces was markedly reduced 24 and 72 h post-seeding compared to smooth surfaces (p < 0.01). Cells were cuboidal or spherical after 72h on super-hydrophobic surfaces, and exhibited numerous surface microvilli with fluff-base polarity, while cells on smooth surfaces exhibited morphological characteristics of EMT. Expression levels of the α-SMA and vimentin were reduced on super-hydrophobic surfaces compared to smooth surfaces. Super-hydrophobic silicon inhibits proliferation, adhesion, and EMT of hLECs, properties that may prevent fibrosis following cataract surgery.


Assuntos
Diferenciação Celular/fisiologia , Células Epiteliais/fisiologia , Lentes Intraoculares , Elastômeros de Silicone , Linhagem Celular , Transição Epitelial-Mesenquimal , Humanos
14.
Growth Factors ; 33(2): 149-59, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25707536

RESUMO

In this study, we investigated the protective effect of mouse nerve growth factor (NGF) on retinal ganglion cell (RGC) injury induced by retinal ischemia-reperfusion (RIR) in rats and explored its possible mechanisms of action. RIR caused a significant injury to RGCs and an obvious impairment of the inner retina functions, which could be seen from flash electroretinogram and flash visual evoked potential recordings. RIR also increased the expression of the apoptotic protein Bax while decreasing the expression of Bcl-2 and the phosphorylation of protein kinase B (Akt) in RGCs. Preinjection (i.m.) of NGF for 22 d reversed the injury induced by RIR and ameliorated the inner retina functions. NGF also reduced the expression of Bax and reversed the reduction of Bcl-2 and the phosphorylated Akt induced by RIR. These results indicate that NGF produces a neuroprotective effect on RGCs against RIR injury and the protective effect of NGF is mainly mediated by the PI-3K/Akt signaling pathway.


Assuntos
Fator de Crescimento Neural/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Doenças Retinianas/prevenção & controle , Células Ganglionares da Retina/efeitos dos fármacos , Animais , Apoptose , Eletrorretinografia , Potenciais Evocados Visuais , Feminino , Masculino , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Doenças Retinianas/patologia , Visão Ocular , Proteína X Associada a bcl-2/metabolismo
16.
Zhong Yao Cai ; 37(6): 1014-20, 2014 Jun.
Artigo em Zh | MEDLINE | ID: mdl-25470969

RESUMO

OBJECTIVE: To study the protective effect and possible mechanisms of Dihydromyricetin(DMY)on PC12 cells injury in- duced by sodium nitroprusside( SNP). METHODS: SNP toxicity cellular model was established using PC12 cells treated with SNP. Cell via- bility was determined by MTT assay. The apoptosis of treated cells was detected by Hoechst Staining. Effect of DMY on accumulation of ROS in PC12 cells induced by SNP was detected by fluorometric analysis. The pathways involved were studied by kinase specific inhibi- tors; The level of phosphorylated Akt and ERK1/2 was detected by Western blot with specific phosphor-antibodies. RESULTS: SNP in- duced the apoptosis of PC12 cells in a dose-dependent manner. DMY dose-dependently protected PC12 cells from injury induced by SNP. Hoechst staining indicated that SNP decreased the number of viable cells and induced shrinkage and aggregation of the nucleus, whereas DMY attenuiated the toxic effects of SNP. The level of ROS induced by SNP in PC12 cells was decreased gradually by DMY. PI3K specific inhibitor LY294002 and the MAPK pathway specific inhibitor PD98059 attenuated the protective effect of DMY on SNP-induced injury of PC12 cells. However, the effect of DMY could be blocked by LY294002 and PD98059 respectively. CONCLUSION: DMY possesses protective effect against apoptosis induced by SNP in PC12 cells,and its mechanisms may be partially related with Akt and ERK1/2 signaling.


Assuntos
Citoproteção/efeitos dos fármacos , Flavonóis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose , Western Blotting , Nitroprussiato , Células PC12 , Fosfatidilinositol 3-Quinases , Fosforilação , Ratos , Transdução de Sinais
17.
Exp Anim ; 73(1): 20-28, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-37460311

RESUMO

Nonhuman primates are important research models for basic vision research, preclinical pathogenesis, and treatment studies due to strong similarities in retinal structure and function with humans. We compared retinal parameters between 10 healthy normal rhesus macaques (Macaca mulatta) and 10 cynomolgus macaques (Macaca fascicularis) by optical coherence tomography and electroretinography. The Heidelberg Spectralis® HRA+OCT and Roland multifocal electrophysiometer were used to analyze retinal morphology, multifocal electroretinograms (mfERGs), and full-field electroretinograms (ff-ERGs). Mean retinal thickness was lowest in the central fovea of macaques and did not differ significantly between species, but the retinal thicknesses of the nerve fiber ganglion cell layer and the inner plexiform layer were significantly different. The amplitude density of the N1 wave was lower in rhesus macaques than in cynomolgus macaques in ring and quadrant areas. Dark-adapted 3.0 oscillatory potentials (reflection of amacrine cell activity) and light-adapted 30-hz flicker ERG (a sensitive cone-pathway-driven response) waveforms of the ff-ERG were similar in both species, while the times to peaks in dark-adapted 0.01 ERG (the rod-driven response of bipolar cells) and dark-adapted 3.0 ERG (combined rod and cone system responses) as well as the implicit times of the a- and b-waves in light-adapted 3.0 ERG (the single-flash cone response) were substantially different. This study provides normative retinal parameters for nonhuman primate research on basic and clinical ophthalmology, as well as a reference for researchers in the appropriate selection of rhesus or cynomolgus macaques as models for ophthalmology studies.


Assuntos
Eletrorretinografia , Retina , Humanos , Animais , Macaca mulatta , Macaca fascicularis , Retina/fisiologia , Eletrorretinografia/métodos , Neurônios
18.
Water Res ; 257: 121707, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38705067

RESUMO

Solar steam generation (SSG) using hydrogels is emerging as a promising technology for clean water production. Herein, a novel oxygen-doped microporous carbon hydrogel (OPCH), rich in hydrophilic groups and micropores, has been synthesized from microalgae to optimize SSG. OPCH outperforms hydrogels with hydrophobic porous carbon or nonporous hydrophilic biochar, significantly reducing water's evaporation enthalpy from 2216.06 to 1107.88 J g-1 and activating 42.3 g of water per 100 g for evaporation, resulting in an impressive evaporation rate of 2.44 kg m-2 h-1 under one sun. A detailed investigation into the synergistic effects of hydrophilic groups and micropores on evaporation via a second derivative thermogravimetry method revealed two types of bonded water contributing to enthalpy reduction. Molecular dynamics simulations provided further insights, revealing that the hydrophilic micropores considerably decrease both the number and the lifetime of hydrogen bonds among water molecules. This dual effect not only reduces the energy barrier for evaporation but also enhances the kinetic energy needed for the phase transition, significantly boosting the water evaporation process. The sustained high evaporation rates of OPCH, observed across multiple cycles and under varying salinity conditions, underscore its potential as a highly efficient and sustainable solution for SSG applications.


Assuntos
Carbono , Hidrogéis , Interações Hidrofóbicas e Hidrofílicas , Vapor , Água , Hidrogéis/química , Carbono/química , Porosidade , Água/química , Simulação de Dinâmica Molecular
19.
Int J Biol Macromol ; 274(Pt 2): 133227, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38897512

RESUMO

This study aimed to develop an ammonia and pH super-sensitive label by incorporating methyl red and bromothymol blue (MR-BTB, MB) into gellan gum/sodium carboxymethyl cellulose (GG/CMC-Na, GC). Furthermore, E-nose as an auxiliary tool combined with the labels to monitor meat freshness. Results showed that MB had more color change than pure MR or BTB, and the detection limit of ammonia about the MR-BTB (1:2) group was only 2.82 ppm. The addition of MB significantly increased tensile strength, moisture content, and water solubility, but decreased elongation at break and transmittance of the GC label (p < 0.05). The result of FTIR and SEM indicated the formation of hydrogen bonds and well compatibility between MB and GC. Furthermore, the color of the GC-10.0MB label was constantly obviously changing during meat storage, indicating that the GC-10.0MB label had great potential for monitoring the freshness of the lamb meat. A high correlation was found between ΔE of GC-10.0MB label and TVB-N (R2 = 0.9092) and pH (R2 = 0.9114) of meat. Interestingly, the high correlation between ΔE of GC-10.0 MB label and the response value of S2 (R2 = 0.7531), S6 (R2 = 0.9921), and S7 sensor (R2 = 0.8325) of E-nose was also found.

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