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1.
BMC Public Health ; 24(1): 1928, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026227

RESUMO

BACKGROUND: The association between sarcopenia and cardiovascular disease (CVD) is well known. However, the clinical diagnosis of sarcopenia is complex and not suitable for early clinical identification and prevention of CVD. Relative muscle strength (RMS) is a relatively quantitative and straightforward indicator, but its association with CVD remains unclear. Hence, the objective of this research was to investigate the correlation between RMS and CVD incidence. METHODS: This was a cross-sectional study, using data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011. CVD events were assessed through self-reported physician diagnoses. The RMS was determined by dividing the maximum grip strength by the appendicular skeletal muscle mass (ASM). This study used multivariate logistic regression and restricted cubic spline (RCS) curves to explore the correlation between RMS and CVD incidence. Additionally, we conducted subgroup analyses to provide additional evidence supporting the association between the two variables. RESULTS: A total of 8,733 people were included in our study, with 1,152 (13.19%) CVD patients and 7,581 (86.81%) non-CVD patients. When the data were grouped according to quartiles (Q) of RMS, the inverse association between CVD and RMS remained statistically significant even after controlling for all potential confounding factors. Compared with participants in Q1 of RMS, the ORs (95% CIs) of CVD among those in Q2-Q4 were 0.99 (0.83, 1.17), 0.81 (0.67, 0.98), and 0.70 (0.57, 0.85), respectively. Moreover, the RCS results showed a negative linear correlation between the RMS and CVD incidence (P for nonlinearity = 0.555). Subgroup analysis revealed no significant interaction in any of the groups except for the sex group (P for interaction = 0.046). CONCLUSION: Our study indicated a stable negative correlation between RMS and CVD incidence. RMS is helpful for the early identification and prevention of CVD.


Assuntos
Doenças Cardiovasculares , Força Muscular , Humanos , China/epidemiologia , Doenças Cardiovasculares/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Força Muscular/fisiologia , Incidência , Estudos Longitudinais , Sarcopenia/epidemiologia
2.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2689-2698, 2024 May.
Artigo em Zh | MEDLINE | ID: mdl-38812169

RESUMO

This study aims to prepare co-loaded indocyanine green(ICG) and elemene(ELE) nano-emulsion(NE) in situ gel(ICG-ELE-NE-gel) and evaluate its physicochemical properties and antitumor activity in vitro. ICG-ELE-NE-gel was prepared by aqueous phase titration and cold solution methods, followed by characterization of the morphology, particle size, corrosion, and photothermal conversion characteristics. The human breast cancer MCF-7 cells were taken as the model, combined with 808 nm laser irradia-tion. Cell inhibition rate test and cell uptake test were performed. ICG-ELE-NE was spherical and uniform in size. The average particle size and Zeta potential were(85.61±0.35) nm and(-21.4±0.6) mV, respectively. The encapsulation efficiency and drug loading rate were 98.51%±0.39% and 10.96%±0.24%, respectively. ICG-ELE-NE-gel had a good photothermal conversion effect and good photothermal stability. The dissolution of ICG-ELE-NE-gel had both temperature and pH-responsive characteristics. Compared with free ELE, ICG-ELE-NE-gel combined with near-infrared light irradiation significantly enhanced the inhibitory effect on MCF-7 cells and could be uptaken in large amounts by MCF-7 cells. ICG-ELE-NE-gel was successfully prepared, and its antitumor activity was enhanced after 808 nm laser irradiation.


Assuntos
Neoplasias da Mama , Proliferação de Células , Emulsões , Verde de Indocianina , Humanos , Verde de Indocianina/química , Células MCF-7 , Emulsões/química , Proliferação de Células/efeitos dos fármacos , Feminino , Tamanho da Partícula , Géis/química , Nanopartículas/química , Composição de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Portadores de Fármacos/química
3.
EMBO Rep ; 22(6): e51649, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33855783

RESUMO

Pathological TDP-43 aggregation is characteristic of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP); however, how TDP-43 aggregation and function are regulated remain poorly understood. Here, we show that O-GlcNAc transferase OGT-mediated O-GlcNAcylation of TDP-43 suppresses ALS-associated proteinopathies and promotes TDP-43's splicing function. Biochemical and cell-based assays indicate that OGT's catalytic activity suppresses TDP-43 aggregation and hyperphosphorylation, whereas abolishment of TDP-43 O-GlcNAcylation impairs its RNA splicing activity. We further show that TDP-43 mutations in the O-GlcNAcylation sites improve locomotion defects of larvae and adult flies and extend adult life spans, following TDP-43 overexpression in Drosophila motor neurons. We finally demonstrate that O-GlcNAcylation of TDP-43 promotes proper splicing of many mRNAs, including STMN2, which is required for normal axonal outgrowth and regeneration. Our findings suggest that O-GlcNAcylation might be a target for the treatment of TDP-43-linked pathogenesis.


Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Esclerose Lateral Amiotrófica/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Splicing de RNA , RNA Mensageiro/genética
4.
J Nanobiotechnology ; 21(1): 210, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37408007

RESUMO

Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/metabolismo , Interferência de RNA , Neoplasias Encefálicas/tratamento farmacológico , Nanomedicina , Biomimética , RNA Interferente Pequeno , Hipóxia/tratamento farmacológico , Linhagem Celular Tumoral
5.
Eur Arch Psychiatry Clin Neurosci ; 272(2): 235-255, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33615398

RESUMO

The study aimed to evaluate the efficacy of group cognitive behavioural therapy (CBT) in medicated adults with attention-deficit/hyperactivity disorder (ADHD) with a multidimensional evaluation and follow-up to week 36. Ninety-eight adult ADHD were randomly allocated to the CBT combined with medication (CBT + M) group or the medication (M) only group. The primary endpoint was the ADHD-Rating Scale (ADHD-RS). Secondary endpoints included emotional symptoms, self-esteem, automatic thoughts, quality of life (QoL), and executive function (EF). The outcome measures were obtained at baseline (T1), after the 12-week CBT treatment (T2), and at two follow-up time points (week 24, T3, and week 36, T4). Compared to the M-only group, the patients in the CBT + M group showed an overall significantly greater reduction from baseline in ADHD core symptoms (ADHD-RS total score at T3, and inattention subscale at T2 and T3), depression and anxiety symptoms (T2-T4), state anxiety (T2 and T3) and trait anxiety (T2), automatic thoughts questionnaire at T3, and QoL (physical domain, psychological domain, and social domain, most significant at T3 and weakened at T4). These findings further confirmed the efficacy of CBT on multiple dimensions and verified improvements in automatic thinking in adult ADHD. The superiority of the combination treatment mainly manifested in reduced inattention, emotional symptoms, and maladaptive thoughts and improved QoL. Trial registration number ChiCTR1900021705 (March-05-2019).


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Terapia Cognitivo-Comportamental , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Terapia Cognitivo-Comportamental/métodos , Humanos , Resultado do Tratamento
6.
Langmuir ; 36(19): 5126-5133, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32336103

RESUMO

Iron incorporation is essential for the record activity of NiFe-(oxy)hydroxides to oxygen evolution reaction (OER), but the details of how Fe affects catalysis remain under active investigation. In this work, we present a double thin-layer strategy for finding unique and solid evidence for the role of Fe in the OER mechanism. A thin-layer catalyst of a few nanometers of thickness was deposited on a Ni substrate and a thin-layer electrolyte of 0.1 mm thickness was created using a thin-layer spectroelectrochemical cell. The OER activity, the catalyst composition, and the electrolyte species were investigated together as a function of the Fe deposition time. The results show that trace Fe incorporation favors the formation of ß-NiOOH in the thin-layer catalyst and effectively suppresses the dissolution of NiOOH into the electrolyte. The results of double-potential step chronoabsorptometry and cyclic voltabsorptometry demonstrate the potential-dependent formation of a Ni3+ intermediate in the electrolyte and, more importantly, the dissolution suppression effect due to Fe incorporation. These findings link the role of Fe in OER catalysis to the increased insolubility of Ni3+ active sites and highlight the importance of paying close attention to the active-site stability of an electrocatalyst impaired by the electrolyte at a reaction potential.

7.
BMC Plant Biol ; 19(1): 506, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747904

RESUMO

BACKGROUND: Ethylene-responsive factors (ERFs) play important roles in plant growth and development and the response to adverse environmental factors, including abiotic and biotic stresses. RESULTS: In the present study, we identified 160 soybean ERF genes distributed across 20 chromosomes that could be clustered into eight groups based on phylogenetic relationships. A highly ABA-responsive ERF gene, GmERF75, belonging to Group VII was further characterized. Subcellular localization analysis showed that the GmERF75 protein is localized in the nucleus, and qRT-PCR results showed that GmERF75 is responsive to multiple abiotic stresses and exogenous hormones. GmERF75-overexpressing Arabidopsis lines showed higher chlorophyll content compared to WT and mutants under osmotic stress. Two independent Arabidopsis mutations of AtERF71, a gene homologous to GmERF75, displayed shorter hypocotyls, and overexpression of GmERF75 in these mutants could rescue the short hypocotyl phenotypes. Overexpressing GmERF75 in soybean hairy roots improved root growth under exogenous ABA and salt stress. CONCLUSIONS: These results suggested that GmERF75 is an important plant transcription factor that plays a critical role in enhancing osmotic tolerance in both Arabidopsis and soybean.


Assuntos
Glycine max/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/fisiologia , Etilenos/metabolismo , Expressão Gênica , Hipocótilo/genética , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/fisiologia , Pressão Osmótica , Fenótipo , Filogenia , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/fisiologia , Glycine max/crescimento & desenvolvimento , Glycine max/fisiologia , Estresse Fisiológico , Fatores de Transcrição/genética
8.
Int J Mol Sci ; 20(6)2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30875808

RESUMO

A novel rice lesion mimic mutant (LMM) was isolated from the mutant population of Japonica rice cultivar Hitomebore generated by ethyl methane sulfonate (EMS) treatment. Compared with the wild-type (WT), the mutant, tentatively designated E40, developed necrotic lesions over the whole growth period along with detectable changes in several important agronomic traits including lower height, fewer tillers, lower yield, and premature death. To understand the molecular mechanism of mutation-induced phenotypic differences in E40, a proteomics-based approach was used to identify differentially accumulated proteins between E40 and WT. Proteomic data from isobaric tags for relative and absolute quantitation (iTRAQ) showed that 233 proteins were significantly up- or down-regulated in E40 compared with WT. These proteins are involved in diverse biological processes, but phenylpropanoid biosynthesis was the only up-regulated pathway. Differential expression of the genes encoding some candidate proteins with significant up- or down-regulation in E40 were further verified by qPCR. Consistent with the proteomic results, substance and energy flow in E40 shifted from basic metabolism to secondary metabolism, mainly phenylpropanoid biosynthesis, which is likely involved in the formation of leaf spots.


Assuntos
Metanossulfonato de Etila/efeitos adversos , Redes Reguladoras de Genes , Oryza/crescimento & desenvolvimento , Proteômica/métodos , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Oryza/efeitos dos fármacos , Oryza/genética , Fenótipo , Doenças das Plantas/induzido quimicamente , Doenças das Plantas/genética , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Metabolismo Secundário
9.
BMC Plant Biol ; 18(1): 320, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509166

RESUMO

BACKGROUND: Abiotic stress severely influences plant growth and development. MYB transcription factors (TFs), which compose one of the largest TF families, play an important role in abiotic stress responses. RESULT: We identified 139 soybean MYB-related genes; these genes were divided into six groups based on their conserved domain and were distributed among 20 chromosomes (Chrs). Quantitative real-time PCR (qRT-PCR) indicated that GmMYB118 highly responsive to drought, salt and high temperature stress; thus, this gene was selected for further analysis. Subcellular localization revealed that the GmMYB118 protein located in the nucleus. Ectopic expression (EX) of GmMYB118 increased tolerance to drought and salt stress and regulated the expression of several stress-associated genes in transgenic Arabidopsis plants. Similarly, GmMYB118-overexpressing (OE) soybean plants generated via Agrobacterium rhizogenes (A. rhizogenes)-mediated transformation of the hairy roots showed improved drought and salt tolerance. Furthermore, compared with the control (CK) plants, the clustered, regularly interspaced, short palindromic repeat (CRISPR)-transformed plants exhibited reduced drought and salt tolerance. The contents of proline and chlorophyll in the OE plants were significantly greater than those in the CK plants, whose contents were greater than those in the CRISPR plants under drought and salt stress conditions. In contrast, the reactive oxygen species (ROS) and malondialdehyde (MDA) contents were significantly lower in the OE plants than in the CK plants, whose contents were lower than those in the CRISPR plants under stress conditions. CONCLUSIONS: These results indicated that GmMYB118 could improve tolerance to drought and salt stress by promoting expression of stress-associated genes and regulating osmotic and oxidizing substances to maintain cell homeostasis.


Assuntos
Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Agrobacterium/metabolismo , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Desidratação , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/fisiologia , Raízes de Plantas/microbiologia , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Estresse Salino , Glycine max/genética , Glycine max/metabolismo , Glycine max/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia
10.
Lipids Health Dis ; 16(1): 85, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-28464894

RESUMO

BACKGROUND: The novel compound XH601 is a synthesized derivative of formononetin. The present study was to investigate the hypolipidemia effect and potential mechanism of XH601. METHODS: Male Golden Syrian hamsters were induced by high-fat diet (HFD) for eight weeks and the hyperlipidemic model was established successfully. After XH601 treatment, serum and hepatic biochemistry parameters of hamsters were detected and the effect of XH601 on adipose tissue was also analyzed. Furthermore, 3 T3-L1 cell differentiation by Oil-Red-O staining was observed and the mRNA and protein expression of peroxisome proliferator-activated receptors (PPARs) were measured by qRT-PCR and Western-blot in mature adipocytes. RESULTS: The in vivo results suggest that XH601 significantly decreased the adipose weight and levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), apolipoprotein B (Apo-B), apolipoprotein E (Apo-E), while increased serum high-density lipoprotein (HDL-C). The in vitro results implied that XH601 up-regulated the mRNA and protein expression of both PPARα and PPARß/δ in a dose-dependent manner. CONCLUSIONS: The study suggests that XH601 exhibited strong ability to improve the dyslipidemia in hamsters fed with high-fat diet. The potential mechanism of XH601 was associated with the up-regulation of PPARα and PPARß/δ mRNA and protein expression.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Isoflavonas/farmacologia , PPAR alfa/agonistas , PPAR delta/agonistas , PPAR beta/agonistas , Células 3T3-L1 , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Apolipoproteínas B/sangue , Apolipoproteínas E/sangue , Diferenciação Celular , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cricetinae , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Masculino , Mesocricetus , Camundongos , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR delta/genética , PPAR delta/metabolismo , PPAR beta/genética , PPAR beta/metabolismo , RNA Mensageiro/agonistas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Triglicerídeos/sangue
11.
Zhongguo Zhong Yao Za Zhi ; 42(7): 1344-1349, 2017 Apr.
Artigo em Zh | MEDLINE | ID: mdl-29052397

RESUMO

To study 48 h processing time of Polygoni Multiflori Radix on its contents and changes of chemical components. HPLC was used to determine the contents of various components in 22 Polygoni Multiflori Radix samples with different processing time, and then the fingerprint similarity analysis and clustering analysis were used for characteristics analysis. Results showed that the similarity was between 0.9-1.0, with good correlation between the samples. In the clustering analysis, the 22 Polygoni Multiflori Radix and processed Polygoni Multiflori Radix samples were classified into 4 types according to the composition changes. The results demonstrated that 4-5 h was the best processing time, providing references for quality control and further study of Polygoni Multiflori Radix.


Assuntos
Medicamentos de Ervas Chinesas/química , Polygonum/química , Cromatografia Líquida de Alta Pressão , Raízes de Plantas/química , Controle de Qualidade
12.
Phytother Res ; 29(8): 1259-64, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25963314

RESUMO

Rhei Radix et Rhizoma was one of the commonly used traditional Chinese medicines, and the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata was the basic herb pair applied in many Chinese traditional prescription. Rhubarb anthraquinones were the main bioactive materials of Rhei Radix et Rhizoma. To elucidate the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata, the pharmacokinetics of rhubarb anthraquinones as the main marker constituents were investigated. In the present study, pharmacokinetic differences of rhubarb anthraquinones were detected after oral administration of extract of Rheum palmatum L. and compatibility with Aconitum carmichaelii Debx. After oral administration, no difference of peak time can be found for anthraquinones between rhubarb group and compatibility group. But Cmax and area under the curve of aloe-emodin, emodin and chrysophanol in compatibility group were significantly higher than that in rhubarb group. Although the Cmax of rhein in compatibility group was much lower than that in rhubarb group, the area under the curve value was similar in two groups. The clearance and t1/2 of rhubarb anthraquinone were also changed after compatibility. The change of pharmacokinetics characteristics of rhubarb anthraquinone after compatibility may be caused by the drug-drug interaction medicated by chemical reaction and cytochromes P450.


Assuntos
Aconitum/química , Antraquinonas/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Rheum/química , Administração Oral , Animais , Antraquinonas/sangue , Interações Medicamentosas , Emodina , Masculino , Extratos Vegetais/farmacocinética , Raízes de Plantas/química , Ratos Sprague-Dawley , Rizoma/química
13.
Zhongguo Zhong Yao Za Zhi ; 40(13): 2656-60, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26697695

RESUMO

This paper is aim to investigate the pharmacokinetics and absolute bioavailability of neoline in Beagle dogs, and provide a theoretical basis for further study. Ethyl acetate was used for liquid-liquid extracting after 10% ammonia alkalizing. The method of UPLC-Q-TOF-MS was established for the determination of neoline plasma concentrations. Beagle dogs were orally or intravenously administered with neoline for pharmacokinetic and absolute bioavailability study. Good linear relationship of neoline was found over the range of 0.1-4 mg x L(-1) (R2 = 0.9982) and 2-100 microg x L(-1) (R2 = 0.9945). Intra-and inter-day precision, expressed as the relativestandard (RSD) were less than 5.0%. Accuracy, expressed as the relative error (RE) was within 90.0%-115%. The recovery of neoline in dog plasma was more than 80%. After 6 mg x kg(-1) for ig and 1 mg x kg(-1) for iv administration of neoline, the main pharmacokinetic parameters were analyzed with Winnonlin software. t(1/2) were (313.88 +/- 63.18), (236.33 +/- 229.84) min, and AUC(0-infinity) were (58,027.40 +/- 14,132.69), (473,578.02 +/- 82,333.08) min x microg x L(-1) for ig and iv administration respectively. The absolute bioavail ability was (73.15 +/- 10.29) %. The method of UPLC-Q-TOF-MS described in the report was sensitive, reliable and specific, and suitable for pharmacokinetic study of neoline in Beagle dog. The high absolute bioavailability of neoline in dog suggested good absorption of neline which was worth of further investigation.


Assuntos
Aconitina/análogos & derivados , Aconitina/química , Aconitina/farmacocinética , Animais , Disponibilidade Biológica , Cães , Estabilidade de Medicamentos , Feminino , Masculino
14.
Sci China Life Sci ; 67(6): 1089-1105, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38842635

RESUMO

Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or homologous recombination (HR). Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency. yKu70 and Rfa1 bind H3K36me2- or H3K36me3-modified peptides and chromatin, respectively. Disrupting these interactions impairs yKu70 and Rfa1 recruitment to damaged H3K36me2- or H3K36me3-rich loci, increasing DNA damage sensitivity and decreasing repair efficiency. Conversely, H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress. Importantly, human KU70 and RPA1, the homologs of yKu70 and Rfa1, exclusively associate with H3K36me2 and H3K36me3 in a conserved manner. These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways, highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Histonas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Histonas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Humanos , Metilação , Autoantígeno Ku/metabolismo , Autoantígeno Ku/genética , Proteína de Replicação A/metabolismo , Proteína de Replicação A/genética , Recombinação Homóloga , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Reparo do DNA , Cromatina/metabolismo , Cromatina/genética
15.
Front Psychiatry ; 14: 1200522, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547201

RESUMO

Background/objectives: Adults with attention-deficit/hyperactivity disorder (ADHD) have more maladaptive cognitions, emotional problems and a poorer quality of life (QoL). A verification of the psychological model in clinical samples is needed for a better understanding of the mechanisms of ADHD diagnosis on QoL via maladaptive cognitions, emotional symptoms, and their interactions. Methods: 299 ADHD participants and 122 healthy controls were recruited. ADHD core symptoms, maladaptive cognitions, emotional symptoms and psychological QoL were rated. Pearson's correlation and structural equation modeling were analyzed to explore the relationship and influence of ADHD diagnosis on QoL. Results: More maladaptive cognitions, emotional symptoms, and poorer QoL were found in the ADHD group, and the dysfunctional attitudes were on par between ADHD with or without medication (p = 0.368). Moderate to strong correlations were found between emotional symptoms, maladaptive cognitions and QoL, and ADHD core symptoms presented correlations among the above scores (r = 0.157 ~ 0.416, p < 0.01) in ADHD participants. The influence of ADHD diagnosis on QoL was mediated through maladaptive cognitions, emotional symptoms, and their bidirectional interactions (p < 0.05), especially those with stable medication. Conclusion: Our study is the first to verify the psychological model in adults with ADHD in China. The findings determined the direct influence of ADHD diagnosis on QoL and the indirect influence through maladaptive cognitions, emotional symptoms, and their interactions, emphasizing the importance of interventions for emotional symptoms and maladaptive cognitions for ADHD patients both with or without medication for a better QoL outcome.

16.
Front Oncol ; 12: 882202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912180

RESUMO

Background: The development of a new strategy to overcome chemoresistance to hepatocellular carcinoma (HCC) treatment is a long-standing issue. We have previously found that upregulated SETD3 levels are closely correlated with HCC. This study aims to explore the mechanism underlying how upregulation of SETD3 promotes liver carcinogenesis. Methods: RNA-Sequencing analysis was used to explore the correlation of SETD3 with regulatory targets. In vitro assays including cell proliferation and migration were performed to study the oncogenic roles of SETD3 and PLK1. Western blotting, immunohistochemical staining, and blood biochemical assays were performed to examine protein expression or pathological index in tumor tissues and mice liver tissues. Luciferase reporter system and chromatin immunoprecipitation assays were used to explore the mechanism. Results: We revealed that SETD3 regulates gene expression in subgroups, including cell division, cell proliferation, and cell cycle, in hepatocellular tumor cells. We found that SETD3 upregulation is associated with elevated PLK1 level in both hepatic tumor cells and clinical liver tissues. We further showed that overexpression of SETD3 promoted tumor cell proliferation and migration, whereas inhibition of PLK1 activity attenuated these phenotypes caused by SETD3. By taking advantage of the Sleep Beauty transposase system, we confirmed that upregulated mouse Setd3 promoted hepatic carcinogenesis in situ, but knockdown of mouse Plk1 mitigated Setd3-promoted tumorigenesis in mice. Mechanistically, we showed that SETD3 could be recruited to the promoter of PLK1 gene to facilitate PLK1 transcription. Conclusions: Our data demonstrate that elevated SETD3 may promote HCC by enhancing PLK1 expression, which suggests that SETD3 may act as a potential drug target combined with PLK1 inhibition to treat HCC.

17.
ChemSusChem ; 14(18): 3926-3934, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34288529

RESUMO

Platinum usually offers the most effective active center for hydrogen evolution reaction (HER), because of the optimal trade-off between the adsorption and desorption of hydrogeN atoms (H*) on Pt atoms. Herein, we report an unusual result regarding the active center of a HER catalyst, which was synthesized by electrodepositing traces of Pt nanoparticles (NPs) into a porous nitrogen-rich dodecahedron matrix derived from zeolitic imidazolate framework ZIF-8. With an ultra-low Pt loading of 2.76 µg cm-2 , the N-Pt-bonded catalyst can produce a current density of 117 mA cm-2 for the HER in 1.0 m H2 SO4 at an overpotential of 50 mV, whereas the commercial Pt/C (300 µg cm-2 Pt) can only reach 50 mA cm-2 under the same conditions. Cyclic voltammetry demonstrates that both the H* adsorption and the Pt oxidation are not allowed to occur on this catalyst, due to a full surface coverage of the trace Pt NPs by imidazole. The results from the specially designed experiments indicate that the imidazole N atoms may act as proton anchor-sites for the HER due to their electron donor nature. Density functional theory calculations also support a catalytic HER mechanism centered at the Pt-supported N active center, which needs a Gibbs free energy of H* absorption (ΔGH* ) significantly smaller than the absolute value of ΔGH* on the Pt(111) surface. We hope that the results of this study will encourage the research on novel N-centered catalysts for the HER.

18.
J Affect Disord ; 293: 97-108, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34175595

RESUMO

BACKGROUND: Adult attention-deficit/hyperactivity disorder (ADHD) is associated with impaired executive function (EF), depressive/anxiety symptoms, and poor quality of life (QoL). In this study, we aimed to investigate correlations among these variables and to build a simple or serial mediation model for exploring the mechanisms between adult ADHD and QoL. METHODS: This was a cross-sectional study. The sample included 223 participants with ADHD and 54 healthy volunteers. Participants were required to complete the following scales: ADHD Rating Scale (ADHD-RS), Brief Version of the World Health Organization Quality of Life Scale (WHOQOL-BREF), Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS). Correlations among EF, depressive/anxiety symptoms and QoL were analyzed using Pearson correlation. The simple and serial mediation models were analyzed using PROCESS (version 3.3). RESULTS: The correlations between EF and QoL, depressive/anxiety symptoms and QoL, and depressive/anxiety symptoms and EF were statistically significant. In ADHD adults with comorbidities, the correlation coefficients were between -0.19 and -0.47, -0.20 and -0.62, 0.28 and 0.50, respectively. In simple mediation models, EF and depressive/anxiety symptoms were significant mediators respectively between ADHD and QoL, respectively. In a serial two-mediator model, ADHD could affect QoL indirectly via EF and then via depressive/anxiety symptoms significantly. LIMITATIONS: The average age was young, the degree of education was high, and only self-reported scales were relied on. CONCLUSIONS: There is a mutual effect between EF and emotional symptoms. This was the first study to build a serial two-mediator model between ADHD and QoL, suggesting the importance of EF and depressive/anxiety symptoms.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Qualidade de Vida , Adulto , Ansiedade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estudos Transversais , Função Executiva , Humanos
19.
Zhonghua Yi Xue Za Zhi ; 90(26): 1827-9, 2010 Jul 13.
Artigo em Zh | MEDLINE | ID: mdl-20979828

RESUMO

OBJECTIVE: To understand the effect of resiniferatoxin on neurogenic bladder by intravesical filling. METHODS: Twenty-four male spinal cord injury patients with an obviously low cystometric capacity, 2 incomplete cervical cord injury, 5 complete thoracic cord injury, 4 incomplete thoracic cord injury, 5 incomplete lumbar cord injury and 8 complete lumbar cord injury were examined. The age range was 24 - 58 years old and the course of disease 1 - 6 years. There were 0.0063 mg/4 ml RTX in each bottle, it was dissolved in 50 ml physiologic saline and was infused into bladder slowly, kept 30 min, then was discharged by intermittent catheterization (IC). During the process, the patients were requested to fill a micturition chart and conduct urodynamic examination before and after the infusion. We regulated that it was utility when the amount of increased maximal cystometric capacity (MCC) exceeded or was 100 ml, otherwise it was invalid. RESULTS: The urodynamic examination before intravesical filling and 1 week after intravesical filling showed that the average MCC were (210 ± 23) ml and (360 ± 30) ml respectively, the average bladder compliance were (17 ± 3) ml/cm H2O and (24 ± 5) ml/cm H2O, there were statistic difference between them (both P < 0.01). The overall effective rate was 62.5%. It lasted 1 - 4 months. CONCLUSION: Resiniferatoxin is effective to increase the cystometric capacity and booster the bladder compliance.


Assuntos
Diterpenos/farmacologia , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Urinária/efeitos dos fármacos , Urodinâmica/efeitos dos fármacos , Adulto , Complacência (Medida de Distensibilidade) , Diterpenos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Bexiga Urinaria Neurogênica/tratamento farmacológico
20.
Autophagy ; 16(5): 956-958, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32054419

RESUMO

Macroautophagy/autophagy is a catabolic process that allows cells to adapt to environmental changes and maintain energy homeostasis. This multistep process is regulated at several levels, including transcriptionally regulating autophagy-related (ATG) gene expression through the action of transcription regulators. Very recently, Wen et al. and we have provided more evidence that two well-known transcription factors regulate different ATG genes to control either nonselective or selective forms of autophagy, respectively. Under nitrogen-starvation conditions, the Spt4-Spt5 complex derepresses ATG8 and ATG41 expression and upregulates bulk autophagy activity. By contrast, under glucose-starvation conditions, the Paf1 complex (the polymerase-associated factor 1 complex, Paf1C) specifically modulates expression of ATG11 and ATG32 to regulate mitophagy. These studies suggest the potential existence of other transcription regulators yet to be discovered that function in the regulation of diverse autophagy pathways.Abbreviations: AMPK: AMP-activated protein kinase; ATG: autophagy-related; NELF: negative elongation factor; Paf1C/PAF1C: polymerase-associated factor 1 complex; RNAP II: RNA polymerase II; Rpd3L: Rpd3 large complex.


Assuntos
Autofagia/fisiologia , Mitofagia/fisiologia , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Histona Desacetilases/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
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