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1.
Mol Cell ; 83(19): 3485-3501.e11, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37802024

RESUMO

p62 is a well-characterized autophagy receptor that recognizes and sequesters specific cargoes into autophagosomes for degradation. p62 promotes the assembly and removal of ubiquitinated proteins by forming p62-liquid droplets. However, it remains unclear how autophagosomes efficiently sequester p62 droplets. Herein, we report that p62 undergoes reversible S-acylation in multiple human-, rat-, and mouse-derived cell lines, catalyzed by zinc-finger Asp-His-His-Cys S-acyltransferase 19 (ZDHHC19) and deacylated by acyl protein thioesterase 1 (APT1). S-acylation of p62 enhances the affinity of p62 for microtubule-associated protein 1 light chain 3 (LC3)-positive membranes and promotes autophagic membrane localization of p62 droplets, thereby leading to the production of small LC3-positive p62 droplets and efficient autophagic degradation of p62-cargo complexes. Specifically, increasing p62 acylation by upregulating ZDHHC19 or by genetic knockout of APT1 accelerates p62 degradation and p62-mediated autophagic clearance of ubiquitinated proteins. Thus, the protein S-acylation-deacylation cycle regulates p62 droplet recruitment to the autophagic membrane and selective autophagic flux, thereby contributing to the control of selective autophagic clearance of ubiquitinated proteins.


Assuntos
Autofagossomos , Proteínas Ubiquitinadas , Camundongos , Ratos , Humanos , Animais , Autofagossomos/metabolismo , Proteínas Ubiquitinadas/metabolismo , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Autofagia/genética , Acilação , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mamíferos/metabolismo
2.
BMC Plant Biol ; 24(1): 145, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38413866

RESUMO

BACKGROUND: Alternative polyadenylation (APA) is an important pattern of post-transcriptional regulation of genes widely existing in eukaryotes, involving plant physiological and pathological processes. However, there is a dearth of studies investigating the role of APA profile in rice leaf blight. RESULTS: In this study, we compared the APA profile of leaf blight-susceptible varieties (CT 9737-613P-M) and resistant varieties (NSIC RC154) following bacterial blight infection. Through gene enrichment analysis, we found that the genes of two varieties typically exhibited distal poly(A) (PA) sites that play different roles in two kinds of rice, indicating differential APA regulatory mechanisms. In this process, many disease-resistance genes displayed multiple transcripts via APA. Moreover, we also found five polyadenylation factors of similar expression patterns of rice, highlighting the critical roles of these five factors in rice response to leaf blight about PA locus diversity. CONCLUSION: Notably, the present study provides the first dynamic changes of APA in rice in early response to biotic stresses and proposes a possible functional conjecture of APA in plant immune response, which lays the theoretical foundation for in-depth determination of the role of APA events in plant stress response and other life processes.


Assuntos
Oryza , Xanthomonas , RNA-Seq , Oryza/metabolismo , Poliadenilação/genética , Resistência à Doença/genética , Estresse Fisiológico , Xanthomonas/fisiologia , Doenças das Plantas/microbiologia , Regulação da Expressão Gênica de Plantas
3.
Theor Appl Genet ; 137(7): 170, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913206

RESUMO

The timely degradation of tapetum, the innermost somatic anther cell layer in flowering plants, is critical for pollen development. Although several genes involved in tapetum development have been characterized, the molecular mechanisms underlying tapetum degeneration remain elusive. Here, we showed that mutation in Abnormal Degraded Tapetum 1 (ADT1) resulted in overaccumulation of Reactive Oxygen Species (ROS) and abnormal anther development, causing earlier tapetum Programmed Cell Death (PCD) and pollen abortion. ADT1 encodes a nuclear membrane localized protein, which is strongly expressed in the developing microspores and tapetal cells during early anther development. Moreover, ADT1 could interact with metallothionein MT2b, which was related to ROS scavenging and cell death regulation. These findings indicate that ADT1 is required for proper timing of tapetum PCD by regulating ROS homeostasis, expanding our understanding of the regulatory network of male reproductive development in rice.


Assuntos
Regulação da Expressão Gênica de Plantas , Mutação , Oryza , Proteínas de Plantas , Pólen , Espécies Reativas de Oxigênio , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Pólen/crescimento & desenvolvimento , Pólen/genética , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Morte Celular , Flores/crescimento & desenvolvimento , Flores/genética , Apoptose
4.
Brain Behav Immun ; 119: 454-464, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38642614

RESUMO

BACKGROUND: Both functional brain imaging studies and autopsy reports have indicated the presence of synaptic loss in the brains of depressed patients. The activated microglia may dysfunctionally engulf neuronal synapses, leading to synaptic loss and behavioral impairments in depression. However, the mechanisms of microglial-synaptic interaction under depressive conditions remain unclear. METHODS: We utilized lipopolysaccharide (LPS) to induce a mouse model of depression, examining the effects of LPS on behaviors, synapses, microglia, microglial phagocytosis of synapses, and the C1q/C3-CR3 complement signaling pathway. Additionally, a C1q neutralizing antibody was employed to inhibit the C1q/C3-CR3 signaling pathway and assess its impact on microglial phagocytosis of synapses and behaviors in the mice. RESULTS: LPS administration resulted in depressive and anxiety-like behaviors, synaptic loss, and abnormal microglial phagocytosis of synapses in the hippocampal dentate gyrus (DG) of mice. We found that the C1q/C3-CR3 signaling pathway plays a crucial role in this abnormal microglial activity. Treatment with the C1q neutralizing antibody moderated the C1q/C3-CR3 pathway, leading to a decrease in abnormal microglial phagocytosis, reduced synaptic loss, and improved behavioral impairments in the mice. CONCLUSIONS: The study suggests that the C1q/C3-CR3 complement signaling pathway, which mediates abnormal microglial phagocytosis of synapses, presents a novel potential therapeutic target for depression treatment.


Assuntos
Complemento C1q , Complemento C3 , Depressão , Modelos Animais de Doenças , Microglia , Fagocitose , Transdução de Sinais , Sinapses , Animais , Complemento C1q/metabolismo , Microglia/metabolismo , Sinapses/metabolismo , Camundongos , Transdução de Sinais/fisiologia , Depressão/metabolismo , Fagocitose/fisiologia , Complemento C3/metabolismo , Masculino , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL
5.
BMC Med Imaging ; 24(1): 48, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373912

RESUMO

INTRODUCTION: The purpose of our study was to differentiate uterine carcinosarcoma (UCS) from endometrioid adenocarcinoma (EAC) by the multiparametric magnetic resonance imaging (MRI) features. METHODS: We retrospectively evaluated clinical and MRI findings in 17 patients with UCS and 34 patients with EAC proven by histologically. The following clinical and pathological features were evaluated: post- or pre-menopausal, clinical presentation, invasion depth, FIGO stage, lymphaticmetastasis. The following MRI features were evaluated: tumor dimension, cystic degeneration or necrosis, hemorrhage, signal intensity (SI) on T2-weighted images (T2WI), relative SI of lesion to myometrium on T2WI, T1WI, DWI, ADCmax, ADCmin, ADCmean (RSI-T2, RSI-T1, RSI-DWI, RSI-ADCmax, RSI-ADCmin, RSI-ADCmean), ADCmax, ADCmin, ADCmean, the maximum, minimum and mean relative enhancement (RE) of lesion to myometrium on the arterial and venous phases (REAmax, REAmin, REAmean, REVmax, REVmin, REVmean). Receiver operating characteristic (ROC) analysis and the area under the curve (AUC) were used to evaluate prediction ability. RESULTS: The mean age of UCS was higher than EAC. UCS occurred more often in the postmenopausal patients. UCS and EAC did not significantly differ in depth of myometrial invasion, FIGO stage and lymphatic metastasis. The anterior-posterior and transverse dimensions were significantly larger in UCS than EAC. Cystic degeneration or necrosis and hemorrhage were more likely occurred in UCS. The SI of tumor on T2WI was more heterogeneous in UCS. The RSI-T2, ADCmax, ADCmean, RSI-ADCmax and RSI-ADCmean of UCS were significantly higher than EAC. The REAmax, REAmin, REAmean, REVmax, REVmin and REVmean of UCS were all higher than EAC. The AUCs were 0.72, 0.71, 0.86, 0.96, 0.89, 0.84, 0.73, 0.97, 0.88, 0.94, 0.91, 0.69 and 0.80 for the anterior-posterior dimension, transverse dimension, RSI-T2, ADCmax, ADCmean, RSI-ADCmax, RSI-ADCmean, REAmax, REAmin, REAmean, REVmax, REVmin and REVmean, respectively. The AUC was 0.997 of the combined of ADCmax, REAmax and REVmax. Our study showed that ADCmax threshold value of 789.05 (10-3mm2/s) can differentiate UCS from EAC with 100% sensitivity, 76.5% specificity, and 0.76 AUC, REAmax threshold value of 0.45 can differentiate UCS from EAC with 88.2% sensitivity, 100% specificity, and 0.88 AUC. CONCLUSION: Multiparametric MRI features may be utilized as a biomarker to distinguish UCS from EAC.


Assuntos
Carcinoma Endometrioide , Carcinossarcoma , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias Uterinas , Feminino , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Carcinoma Endometrioide/diagnóstico por imagem , Estudos Retrospectivos , Neoplasias Uterinas/diagnóstico por imagem , Hemorragia , Necrose , Carcinossarcoma/diagnóstico por imagem
6.
Nucleic Acids Res ; 50(5): 2417-2430, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35191495

RESUMO

Two families of DNA glycosylases (YtkR2/AlkD, AlkZ/YcaQ) have been found to remove bulky and crosslinking DNA adducts produced by bacterial natural products. Whether DNA glycosylases eliminate other types of damage formed by structurally diverse antibiotics is unknown. Here, we identify four DNA glycosylases-TxnU2, TxnU4, LldU1 and LldU5-important for biosynthesis of the aromatic polyketide antibiotics trioxacarcin A (TXNA) and LL-D49194 (LLD), and show that the enzymes provide self-resistance to the producing strains by excising the intercalated guanine adducts of TXNA and LLD. These enzymes are highly specific for TXNA/LLD-DNA lesions and have no activity toward other, less stable alkylguanines as previously described for YtkR2/AlkD and AlkZ/YcaQ. Similarly, TXNA-DNA adducts are not excised by other alkylpurine DNA glycosylases. TxnU4 and LldU1 possess unique active site motifs that provide an explanation for their tight substrate specificity. Moreover, we show that abasic (AP) sites generated from TxnU4 excision of intercalated TXNA-DNA adducts are incised by AP endonuclease less efficiently than those formed by 7mG excision. This work characterizes a distinct class of DNA glycosylase acting on intercalated DNA adducts and furthers our understanding of specific DNA repair self-resistance activities within antibiotic producers of structurally diverse, highly functionalized DNA damaging agents.


Assuntos
Adutos de DNA , DNA Glicosilases , Aminoglicosídeos , Antibacterianos/farmacologia , Dano ao DNA , DNA Glicosilases/metabolismo , Reparo do DNA
7.
J Integr Neurosci ; 23(1): 11, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38287859

RESUMO

Parkinson's disease (PD) is a chronic neurodegenerative disease whose main pathological features are the degeneration of dopamine neurons and deposition of α-synuclein in neurons. At present, the most important treatment strategy for PD is drugs, and one of the most used drugs is levodopa. However, this therapy shows many problems, such as tolerance and long-term effects, so other treatment strategies need to be explored. As a traditional Chinese medicine treatment method with effective and few side effects, electroacupuncture is considered a non-drug therapy. It serves as a novel, promising therapeutic approach for the treatment of PD. In this review, the application and the effects of electroacupuncture on PD have been described. Besides, the underlying molecular mechanisms of electroacupuncture on PD that contribute to protecting dopaminergic neurons and reducing α-synuclein levels have been illustrated, including ① anti-oxidant stress response, ② anti-neuroinflammatory response, ③ up-regulation of neurotrophic factors and reduction of nerve cell apoptosis, ④ down-regulation of endoplasmic reticulum stress and improvement of mitochondrial function, ⑤ improvement of the function of the ubiquitin-proteasome system, ⑥ anti-excitatory toxicity response, ⑦ activation of autophagy, and ⑧ modulation of gut microbiota. Achieving a better understanding of the neuroprotective effects of electroacupuncture on PD will provide a theoretical basis and facilitate the application of electroacupuncture on PD.


Assuntos
Eletroacupuntura , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , alfa-Sinucleína , Fármacos Neuroprotetores/farmacologia , Doenças Neurodegenerativas/patologia , Neurônios Dopaminérgicos/patologia
8.
Molecules ; 29(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38893487

RESUMO

Under-deposit corrosion is widely present in the pipelines of oil and gas production, causing significant corrosion damage. In this paper, a novel electrochemical cathodic-polarization method was carried out to accelerate the formation of CaCO3 scale on a X65 steel surface in a simulated solution containing scaling ions. Subsequently, pre-scaled X65 steel was placed in a high temperature and pressure autoclave to conduct corrosion weight-loss experiments and in situ electrochemical measurements. The study mainly compared the corrosion inhibition behavior of four quaternary ammonium salt corrosion inhibitors, pyridinium quaternary salt (BPC), quinolinium quaternary salt (BQC), 8-hydroxyquinolinium quaternary salt (BHQ) and pyridinium (1-chloromethyl naphthalene) quaternary salt (1-CPN), in a simulated oilfield scale under corrosive conditions. The results of the weight-loss experiments demonstrated that the inhibition efficiencies of the corrosion inhibitors from high to low were as follows: 1-CPN < BHQ < BQC < BPC. The in situ electrochemical measurements showed that the immersion time and type of corrosion inhibitor had a pronounced influence on the corrosion and corrosion inhibition behavior of X65 steel with CaCO3 coating. It was also proved using both EIS and PC that 1-CPN shows the best inhibition performance in all. Lastly, the inhibition mechanism of corrosion inhibitors at under-deposit conditions was analyzed via a surface morphology observation of SEM.

9.
J Transl Med ; 21(1): 223, 2023 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-36973787

RESUMO

BACKGROUND: The prognostic management of bladder cancer (BLCA) remains a great challenge for clinicians. Recently, bulk RNA-seq sequencing data have been used as a prognostic marker for many cancers but do not accurately detect core cellular and molecular functions in tumor cells. In the current study, bulk RNA-seq and single-cell RNA sequencing (scRNA-seq) data were combined to construct a prognostic model of BLCA. METHODS: BLCA scRNA-seq data were downloaded from Gene Expression Omnibus (GEO) database. Bulk RNA-seq data were obtained from the UCSC Xena. The R package "Seurat" was used for scRNA-seq data processing, and the uniform manifold approximation and projection (UMAP) were utilized for downscaling and cluster identification. The FindAllMarkers function was used to identify marker genes for each cluster. The limma package was used to obtain differentially expressed genes (DEGs) affecting overall survival (OS) in BLCA patients. Weighted gene correlation network analysis (WGCNA) was used to identify BLCA key modules. The intersection of marker genes of core cells and genes of BLCA key modules and DEGs was used to construct a prognostic model by univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Differences in clinicopathological characteristics, immune microenvironment, immune checkpoints, and chemotherapeutic drug sensitivity between the high and low-risk groups were also investigated. RESULTS: scRNA-seq data were analyzed to identify 19 cell subpopulations and 7 core cell types. The ssGSEA showed that all 7 core cell types were significantly downregulated in tumor samples of BLCA. We identified 474 marker genes from the scRNA-seq dataset, 1556 DEGs from the Bulk RNA-seq dataset, and 2334 genes associated with a key module identified by WGCNA. After performing intersection, univariate Cox, and LASSO analysis, we obtained a prognostic model based on the expression levels of 3 signature genes, namely MAP1B, PCOLCE2, and ELN. The feasibility of the model was validated by an internal training set and two external validation sets. Moreover, patients with high-risk scores are predisposed to experience poor OS, a larger prevalence of stage III-IV, a greater TMB, a higher infiltration of immune cells, and a lesser likelihood of responding favorably to immunotherapy. CONCLUSION: By integrating scRNA-seq and bulk RNA-seq data, we constructed a novel prognostic model to predict the survival of BLCA patients. The risk score is a promising independent prognostic factor that is closely correlated with the immune microenvironment and clinicopathological characteristics.


Assuntos
Análise da Expressão Gênica de Célula Única , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , RNA-Seq , Neoplasias da Bexiga Urinária/genética , Mapeamento Cromossômico , Microambiente Tumoral/genética
10.
J Immunol ; 206(8): 1832-1843, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33789983

RESUMO

CARD9 is an essential adaptor protein in antifungal innate immunity mediated by C-type lectin receptors. The activity of CARD9 is critically regulated by ubiquitination; however, the deubiquitinases involved in CARD9 regulation remain incompletely understood. In this study, we identified ovarian tumor deubiquitinase 1 (OTUD1) as an essential regulator of CARD9. OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-κB and MAPK pathway. OTUD1 deficiency impaired CARD9-mediated signaling and inhibited the proinflammatory cytokine production following fungal stimulation. Importantly, Otud1 -/- mice were more susceptible to fungal infection than wild-type mice in vivo. Collectively, our results identify OTUD1 as an essential regulatory component for the CARD9 signaling pathway and antifungal innate immunity through deubiquitinating CARD9.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Candida albicans/fisiologia , Candidíase/imunologia , Enzimas Desubiquitinantes/metabolismo , Neutrófilos/imunologia , Proteases Específicas de Ubiquitina/metabolismo , Animais , Células Cultivadas , Citotoxicidade Imunológica , Enzimas Desubiquitinantes/genética , Modelos Animais de Doenças , Humanos , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Células RAW 264.7 , Transdução de Sinais , Proteases Específicas de Ubiquitina/genética , Ubiquitinação
11.
Int J Mol Sci ; 24(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38139187

RESUMO

Late spring cold is a disastrous weather condition that often affects early rice seedlings in southern China, limiting the promotion of direct seeding cultivation. However, there are few reports on the effect of these events and on the growth recovery mechanism of rice root systems after rice seedlings are exposed to this stress. This study selected the strong-growth-recovery variety B116 (R310/R974, F17) and the slow-recovery variety B811 (Zhonghui 286) for direct seeding cultivation and exposed them to low temperature and low-light stress to simulate a late spring cold event in an artificial climate chamber. The treatment consisted of 4 days of exposure to a day/night temperature of 14/10 °C and a light intensity of 266 µmol m-2s-1 while the control group was kept at a day/night temperature of 27/25 °C and light intensity of 533 µmol m-2s-1. The results showed that 6 days after stress, the total length, surface area, and volume of B116 roots increased by 335.5%, 290.1%, and 298.5%, respectively, while those of B811 increased by 228.8%, 262.0%, and 289.1%, respectively. In B116, the increase in root fresh weight was 223.1%, and that in B811 was 165.6%, demonstrating rapid root recovery after stress and significant differences among genotypes. The content of H2O2 and MDA in the B116 roots decreased faster than that in the B811 roots after normal light intensity and temperature conditions were restored, and the activity of ROS metabolism enzymes was stronger in B116 roots than in B811 roots. The correlation analysis between the transcriptome and metabolome showed that endogenous signal transduction and starch and sucrose metabolism were the main metabolic pathways affecting the rapid growth of rice seedling roots after exposure to combined stress from low temperature and low light intensities. The levels of auxin and sucrose in the roots of the strong-recovery variety B116 were higher, and this variety's metabolism was downregulated significantly faster than that of B811. The auxin response factor and sucrose synthesis-related genes SPS1 and SUS4 were significantly upregulated. This study contributes to an understanding of the rapid growth recovery mechanism in rice after exposure to combined stress from low-temperature and low-light conditions.


Assuntos
Oryza , Plântula , Plântula/metabolismo , Transcriptoma , Oryza/metabolismo , Temperatura , Peróxido de Hidrogênio/metabolismo , Ácidos Indolacéticos/metabolismo , Metaboloma , Sacarose/metabolismo , Raízes de Plantas/metabolismo
12.
Molecules ; 28(3)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36770908

RESUMO

Food allergies are a serious food safety and public health issue. Soybean, dairy, aquatic, poultry, and nut products are common allergens inducing allergic reactions and adverse symptoms such as atopic dermatitis, allergic eczema, allergic asthma, and allergic rhinitis. Probiotics are assumed as an essential ingredient in maintaining intestinal microorganisms' composition. They have unique physiological roles and therapeutic effects in maintaining the mucosal barrier, immune function, and gastrointestinal tract, inhibiting the invasion of pathogenic bacteria, and preventing diarrhea and food allergies. Multiple pieces of evidence reveal a significant disruptive effect of probiotics on food allergy pathology and progression mechanisms. Thus, this review describes the allergenic proteins as an entry point and briefly describes the application of probiotics in allergenic foods. Then, the role of probiotics in preventing and curing allergic diseases by regulating human immunity through intestinal flora and intestinal barrier, modulating host immune active cells, and improving host amino acid metabolism are described in detail. The anti-allergic role of probiotics in the function and metabolism of the gastrointestinal tract has been comprehensively explored to furnish insights for relieving food allergy symptoms and preventing food allergy.


Assuntos
Dermatite Atópica , Hipersensibilidade Alimentar , Probióticos , Humanos , Hipersensibilidade Alimentar/tratamento farmacológico , Dermatite Atópica/tratamento farmacológico , Alérgenos/uso terapêutico , Probióticos/farmacologia , Probióticos/uso terapêutico , Imunidade , Imunomodulação
13.
Rev Esp Enferm Dig ; 115(9): 529-530, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36562526

RESUMO

Due to low incidence rate of pancreatic duct stones,Authoritative consensus has not been reached regarding therapeutic choices in clinical practice. This article reports the treatment of a young woman with chronic pancreatitis complicated with refractory multiple pancreatic duct stones, which provides clinical experience for treatment and provides a new way to study the pathogenesis of chronic pancreatitis complicated with pancreatic duct stones.


Assuntos
Litotripsia , Pancreatopatias , Pancreatite Crônica , Feminino , Humanos , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Pancreatopatias/complicações , Pancreatite Crônica/complicações , Pancreatite Crônica/diagnóstico por imagem , Pancreatite Crônica/patologia , Colangiopancreatografia Retrógrada Endoscópica
14.
Psychol Med ; 52(1): 48-56, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32501194

RESUMO

BACKGROUND: Major depressive disorder is characterized by a high risk of relapse. We aimed to compare the prophylactic effects of different antidepressant medicines (ADMs). METHODS: PubMed, Cochrane Central Register of Controlled Trials, Embase and the Web of Science were searched on 4 July 2019. A pooled analysis of parametric survival curves was performed using a Bayesian framework. The main outcomes were hazard ratios (HRs), relapse-free survival and mean relapse-free months. RESULTS: Forty randomized controlled trials were included. The 1-year relapse-free survival for ADM (76%) was significantly better than that for placebo (56%). Most of the relapse difference (86.5%) occurred in the first 6 months. Most HRs were not constant over time. Proof of benefit after 6 months of follow-up was not established partially because of small differences between the drug and placebo after 6 months. Almost all studies used an 'enriched' randomized discontinuation design, which may explain the high relapse rates in the first 6 months after randomization. CONCLUSIONS: The superiority of ADM v. placebo was mainly attributed to the difference in relapse rates that occurred in the first 6 months. Our analysis provided evidence that the prophylactic efficacy was not constant over time. A beneficial effect was observed, but the prevention of new episodes after 6 months was questionable. These findings may have implications for clinical practice.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/prevenção & controle , Teorema de Bayes , Antidepressivos/uso terapêutico , Recidiva , Doença Crônica
15.
BMC Geriatr ; 22(1): 511, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729501

RESUMO

BACKGROUND: To explore the optimal Mediterranean diet (MedDiet) adherence score threshold for the association between inflammatory markers and cognitive performance among older adults. METHODS: In this cross-sectional study, we selected data of the elderly (≥ 60 years old) from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 (n = 2830). Participants completed at least one cognitive measurement and two 24-h food recalls. By analyzing the relation between inflammatory markers and cognitive performance using the subdivided MedDiet adherence score, we got the optimal MedDiet adherence score threshold. Then the optimal threshold was used to divide participants into high and low MedDiet adherence groups and multivariate logistic regression models were developed to examine the association between inflammatory markers and cognitive performance in each group. Subgroup analysis was conducted based on gender, race, BMI, physical activity level, and chronic diseases. RESULTS: We chose 4 as the optimal MedDiet adherence score threshold and included these participants whose MedDiet adherence score was 4 or above into the high MedDiet adherence group, while the MedDiet adherence score of the low adherence group was less than 4. We found that the increased white blood cell (WBC) count (OR = 1.44, 95% CI: 1.09-1.90, P = 0.008), neutrophil count (OR = 1.30, 95% CI: 1.03-1.65, P = 0.023), and neutrophil-albumin ratio (NAR) (OR = 1.34, 95% CI: 1.06-1.70, P = 0.012) were all related to a higher risk of low cognitive performance in the low MedDiet adherence group. A higher PLR was linked to a reduced risk of low cognitive performance (OR = 0.86, 95% CI: 0.74-1.00, P = 0.036) in the high MedDiet adherence group. Significant differences were found in the associations of WBC count, neutrophil count and NAR with low cognitive performance between the low and high MedDiet adherence groups (all P < 0.001). The weakened negative association between inflammatory markers and cognitive performance in the high MedDiet adherence group also existed among male, non-Hispanic white, normal-weight, overweight, moderate work activity, moderate recreational activity, non-depression, hypertension, non-hypertension, non-diabetes, non-stroke, non-heart failure, non-coronary heart disease, or non-heart attack subpopulations of older adults. CONCLUSIONS: The optimal threshold for the MedDiet adherence score was 4, and the negative association between inflammation and cognitive performance could be weakened in older adults whose MedDiet adherence score was ≥ 4.


Assuntos
Dieta Mediterrânea , Idoso , Biomarcadores , Cognição , Estudos Transversais , Humanos , Masculino , Inquéritos Nutricionais
16.
Nucleic Acids Res ; 48(2): 709-718, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31713613

RESUMO

DNA interstrand crosslinks (ICLs) induced by the highly genotoxic agent azinomycin B (AZB) can cause severe perturbation of DNA structure and even cell death. However, Streptomyces sahachiroi, the strain that produces AZB, seems almost impervious to this danger because of its diverse and distinctive self-protection machineries. Here, we report the identification of a novel endonuclease-like gene aziN that contributes to drug self-protection in S. sahachiroi. AziN expression conferred AZB resistance on native and heterologous host strains. The specific binding reaction between AziN and AZB was also verified in accordance with its homology to drug binding proteins, but no drug sequestering and deactivating effects could be detected. Intriguingly, due to the high affinity with the drug, AziN was discovered to exhibit specific recognition and binding capacity with AZB-mediated ICL structures, further inducing DNA strand breakage. Subsequent in vitro assays demonstrated the structure-specific endonuclease activity of AziN, which cuts both damaged strands at specific sites around AZB-ICLs. Unravelling the nuclease activity of AziN provides a good entrance point to illuminate the complex mechanisms of AZB-ICL repair.


Assuntos
Proteínas de Transporte/química , DNA/química , Peptídeos e Proteínas de Sinalização Intercelular/química , Proteínas de Transporte/genética , Reagentes de Ligações Cruzadas/química , DNA/genética , Dano ao DNA/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Endonucleases/química , Endonucleases/genética , Humanos , Naftalenos/química , Streptomyces/genética
17.
Biochem Genet ; 60(6): 2268-2285, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35325440

RESUMO

To further understand the molecular mechanism for rice male reproduction, a rice male sterile mutant paa1 was screened from the rice mutant library generated by treatment with 60Coγ-rays. Genetic analysis revealed that paa1 is controlled by a single- recessive nuclear gene, and the anthers of the paa1 mutant were smaller than those of WT plants with a white color. Histological analysis demonstrated that the anthers of the paa1 mutant began to turn abnormal at the microspore stage after meiosis, with abnormal degradation of tapetum, deformed Ubisch bodies, and defective pollen exine. TUNEL assay results also confirmed the delay of tapetum PCD in paa1. Map-based cloning was performed for the PAA1 location. As a result, PAA1 was located in a 88-kb region at the end of chromosome 10, which comprises a total of seven candidate genes, and no genes related to anther development have been reported in this region. The results indicate that PAA1 is an essential gene in regulating tapetum development and pollen/microspore formation after rice meiosis.


Assuntos
Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pólen/genética , Pólen/metabolismo , Meiose/genética , Flores/genética
18.
Small ; 17(6): e2006882, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33470524

RESUMO

The inherent features of covalent organic frameworks (COFs) make them highly attractive for uranium recovery applications. A key aspect yet to be explored is how to improve the selectivity and efficiency of COFs for recovering uranium from seawater. To achieve this goal, a series of robust and hydrophilic benzoxazole-based COFs is developed (denoted as Tp-DBD, Bd-DBD, and Hb-DBD) as efficient adsorbents for photo-enhanced targeted uranium recovery. Benefiting from the hydroxyl groups and the formation of benzoxazole rings, the hydrophilic Tp-DBD shows outstanding stability and chemical reduction properties. Meanwhile, the synergistic effect of the hydroxyl groups and the benzoxazole rings in the π-conjugated frameworks significantly decrease the optical band gap, and improve the affinity and capacity to uranium recovery. In seawater, the adsorption capacity of uranium is 19.2× that of vanadium, a main interfering metal in uranium extraction.

19.
Anal Biochem ; 632: 114390, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560055

RESUMO

Nanobodies (Nbs) as capture antibodies in enzyme-linked immunosorbent assays (ELISAs) is greatly hampered by their poor performance after attaching onto polystyrene microplates. Reasons behind those phenomena remain unknown. One of possible explanation is that Nbs with a single domain might lose their accessibility of paratope when adsorbed on the plates. Increasing their binding sites might improve performance in capture Nbs-based ELISA. In this study, anti-3-phenoxybenzoic acid (3-PBA) Nbs was assembled to trivalent form (Nb3) in tandem with flexible linkers (G4S)3. Direct competitive ELISA on the basis of Nb3 and 3-PBA-horseradish peroxidase was developed for detection of 3-PBA in livestock urine. The ELISA had a half-maximum (IC50) inhibition concentration of 0.51 ng/mL, with a limit of detection of 0.02 ng/mL, which was more sensitive than that of the parental Nb with a IC50 of 2.39 ng/mL. The average recoveries of 3-PBA spiked in swine, sheep and dairy cow urine samples by the assay ranged from 89.52% to 114.25% and agreed well with those of liquid chromatography mass spectrometry (LC-MS). The above results indicated that multivalent Nbs could be treated as the capture antibody in ELISA for routine screening analysis of 3-PBA residues in urine.


Assuntos
Anticorpos/química , Benzoatos/urina , Ensaio de Imunoadsorção Enzimática , Anticorpos de Domínio Único/química , Animais , Bovinos , Ovinos , Suínos
20.
Ther Drug Monit ; 43(6): 797-806, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34780392

RESUMO

BACKGROUND: Paraquat ( PQ) is very poisonous to humans and animals and there is no effective clinical antidote . The efficacy of hemoperfusion (HP) treatment for PQ poisoning remains controversial. To explore new ways to predict the prognosis of patients with acute PQ poisoning and assist in the development of better hemopurification treatment strategies. METHODS: The clinical data of patients who were intoxicated with PQ through contact were diagnosed with PQ poisoning by high-performance liquid chromatography. Samples were collected by the Emergency Intensive Care Unit of the First Affiliated Hospital of Wenzhou Medical University from January 2012 to November 2016. Based on the prognosis, the patients were grouped into survival and death groups. Comparisons of the differences in the clinical indexes were performed, including the initial concentration of PQ at admission, PQ concentration after first HP, the number of HP cartridges used for the first hemoperfusion, whether HP was combined with continuous renal replacement therapy, and the number of concurrent organ injuries between the 2 groups. In addition, data were analyzed using multivariate logistic regression models and receiver operating characteristic curves. Moreover, prognostic factors in patients with acute PQ poisoning were analyzed. RESULTS: Overall, 128 patients with acute PQ poisoning were enrolled in this study. The median plasma PQ concentrations of the patients at admission were 21 and 834 ng/mL (range: 50-1,099,118 ng/mL). The multiple logistic regression model revealed that the initial concentration of PQ and the PQ concentration after the first perfusion were independent risk factors for death in patients with acute PQ poisoning. The PQ concentration in the survival group after the first HP was <516 ng/mL and was mainly distributed at approximately 100 ng/mL. The percentage of patients whose concentration after the first HP was <516 ng/mL in the death group was only 19%. CONCLUSIONS: The initial plasma PQ concentration after admission and PQ concentration after the first HP are risk factors for death in patients with acute PQ poisoning. Moreover, PQ concentration after the first HP had a high predictive value for death. When the initial plasma PQ concentration after admission ranges from 50 ng/mL to 5000 ng/mL, the rapid reduction in plasma PQ concentration after HP treatment could improve the prognosis of patients with acute PQ poisoning.


Assuntos
Hemoperfusão , Venenos , Hemoperfusão/métodos , Humanos , Paraquat , Prognóstico , Curva ROC
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