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1.
Cell Commun Signal ; 22(1): 222, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594767

RESUMO

Csn5 is subunit 5 of the COP9 signalosome (CSN), but the mechanism by which it strictly controls the pathogenicity of pathogenic fungi through autophagy remains unclear. Here, we found that Csn5 deficiency attenuated pathogenicity and enhanced autophagy in Magnaporthe oryzae. MoCSN5 knockout led to overubiquitination and overdegradation of MoTor (the core protein of the TORC1 complex [target of rapamycin]) thereby promoted autophagy. In addition, we identified MoCsn5 as a new interactor of MoAtg6. Atg6 was found to be ubiquitinated through linkage with lysine 48 (K48) in cells, which is necessary for infection-associated autophagy in pathogenic fungi. K48-ubiquitination of Atg6 enhanced its degradation and thereby inhibited autophagic activity. Our experimental results indicated that MoCsn5 promoted K48-ubiquitination of MoAtg6, which reduced the MoAtg6 protein content and thus inhibited autophagy. Aberrant ubiquitination and autophagy in ΔMocsn5 led to pleiotropic defects in the growth, development, stress resistance, and pathogenicity of M. oryzae. In summary, our study revealed a novel mechanism by which Csn5 regulates autophagy and pathogenicity in rice blast fungus through ubiquitination.


Assuntos
Ascomicetos , Virulência , Proteínas , Ubiquitinação , Autofagia
2.
Inflamm Res ; 73(4): 531-539, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38498178

RESUMO

Metabolic remodeling is a key feature of macrophage activation and polarization. Recent studies have demonstrated the role of tricarboxylic acid (TCA) cycle metabolites in the innate immune system. In the current review, we summarize recent advances in the metabolic reprogramming of the TCA cycle during macrophage activation and polarization and address the effects of these metabolites in modulating macrophage function. Deciphering the crosstalk between the TCA cycle and the immune response might provide novel potential targets for the intervention of immune reactions and favor the development of new strategies for the treatment of infection, inflammation, and cancer.


Assuntos
Ciclo do Ácido Cítrico , Macrófagos , Ciclo do Ácido Cítrico/fisiologia , Macrófagos/metabolismo
3.
Am J Emerg Med ; 80: 185-193, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38626653

RESUMO

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a significant cause of mortality and morbidity worldwide. Extracorporeal cardiopulmonary resuscitation (ECPR) is a potential intervention for OHCA, but its effectiveness compared to conventional cardiopulmonary resuscitation (CCPR) needs further evaluation. METHOD: We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov for relevant studies from January 2010 to March 2023. Pooled meta-analysis was performed to investigate any potential association between ECPR and improved survival and neurological outcomes. RESULTS: This systematic review and meta-analysis included two randomized controlled trials enrolling 162 participants and 10 observational cohort studies enrolling 4507 participants. The pooled meta-analysis demonstrated that compared to CCRP, ECPR did not improve survival and neurological outcomes at 180 days following OHCA (RR: 3.39, 95% CI: 0.79 to 14.64; RR: 2.35, 95% CI: 0.97 to 5.67). While a beneficial effect of ECPR was obtained regarding 30-day survival and neurological outcomes. Furthermore, ECPR was associated with a higher risk of bleeding complications. Subgroup analysis showed that ECPR was prominently beneficial when exclusively initiated in the emergency department. Additional post-resuscitation treatments did not significantly impact the efficacy of ECPR on 180-day survival with favorable neurological outcomes. CONCLUSIONS: There is no high-quality evidence supporting the superiority of ECPR over CCPR in terms of survival and neurological outcomes in OHCA patients. However, due to the potential for bias, heterogeneity among studies, and inconsistency in practice, the non-significant results do not preclude the potential benefits of ECPR. Further high-quality research is warranted to optimize ECPR practice and provide more generalizable evidence. Clinical trial registration PROSPERO, https://www.crd.york.ac.uk/prospero/, registry number: CRD42023402211.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidade , Humanos , Reanimação Cardiopulmonar/métodos , Oxigenação por Membrana Extracorpórea/métodos
4.
J Ultrasound Med ; 43(1): 151-160, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37812196

RESUMO

OBJECTIVES: To investigate whether the integration of high-frequency ultrasound (HFUS) to routine clinical examinations could improve diagnostic performance and management decision for pigmented skin tumors. METHODS: Three general practitioners trained previously and a dermatologist independently assessed pigmented skin tumors and rendered management decision based on clinical examinations alone or clinical examinations integrating HFUS. RESULTS: After integrating HFUS, the diagnostic area under the curve (AUC) (0.658-0.693 versus 0.848, all P < .05) and specificity (46.6-58.6% versus 89.7%, all P < .05) for pigmented skin malignancies were improved for general practitioners, meanwhile unnecessary biopsy rate reduced (42.9-53.6% versus 10.7%, P < .001). To the dermatologist, the diagnostic AUC (0.822 versus 0.949, P < .001), sensitivity (81.7% versus 96.7%, P = .012) and specificity (0.828 versus 0.931, P = .031) improved significantly, meanwhile both missed biopsy rate (14.5% versus 4.8%, P = .031) and unnecessary biopsy rate (19.6% versus 7.1%, P = .016) decreased. Additionally, the diagnostic performance of the general practitioner with integrating HFUS could be comparable with the dermatologist based on clinical examinations alone (all P > .05). CONCLUSIONS: As a complementary tool of clinical examinations, HFUS could help physicians differentiate pigmented skin malignancies and manage decision.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Sensibilidade e Especificidade , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Biópsia , Ultrassonografia
5.
Angew Chem Int Ed Engl ; 63(8): e202316454, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38155472

RESUMO

In the chemistry community, catalytic asymmetric synthesis of furan-based compounds bearing both axial and central chirality has proven to be a significant but challenging issue owing to the importance and difficulty in constructing such frameworks. In this work, we have realized the first catalytic asymmetric synthesis of five-five-membered furan-based compounds bearing both axial and central chirality via organocatalytic asymmetric (2+4) annulation of achiral furan-indoles with 2,3-indolyldimethanols with uncommon regioselectivity. By this strategy, furan-indole compounds bearing both axial and central chirality were synthesized in high yields with excellent regio-, diastereo-, and enantioselectivities. Moreover, theoretical calculations were conducted to provide an in-depth understanding of the reaction pathway, activation mode, and the origin of the selectivity.

6.
Carcinogenesis ; 44(5): 418-425, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37209099

RESUMO

Acute myeloid leukaemia (AML) is one of the most lethal cancers of the haematopoietic system with a poorly understood aetiology. Recent studies have shown that aberrant alternative splicing (AS) and a (RBP) regulators are highly associated with the pathogenesis of AML. This study presents an overview of the abnormal AS and differential expression of RNA-binding proteins (RBPs) in AML and further highlights their close relation to the remodelling of the immune microenvironment in AML patients. An in-depth understanding of the regulatory mechanism underlying AML will contribute to the future development of strategies for the prevention, diagnosis and therapy of AML and thus improve the overall survival of patients with AML.


Assuntos
Processamento Alternativo , Leucemia Mieloide Aguda , Humanos , Processamento Alternativo/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Leucemia Mieloide Aguda/patologia , Microambiente Tumoral/genética
7.
Altern Ther Health Med ; 29(3): 127-133, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36689360

RESUMO

Context: The persistent use of anticancer medicines can cause multidrug resistance in many tumors and serious cytotoxicity for healthy cells, including adriamycin (ADR), a treatment for breast cancer (BC). Cell resistance to ADR in patients with recurrent advanced BC can occur. Creating effective treatments that can grapple with multidrug resistance is still challenging. Traditional Chinese medicine (TCM) may offer a solution in D Rhamnose beta-hederin (DRß-H), an oleanane type of triterpenoid saponin. Objective: The study intended to assess the ability of DRß-H to inhibit the ADR resistance of two BC-lineage cell lines, MCF-7 and SUM-1315, and to explore the causal link between DRß-H and the reversal of chemoresistance. Design: The research team performed a cell biology study. Setting: The study took place at laboratory in China. Outcome Measures: The research team: (1) assessed cell viability and the migration and invasion the cell lines; (2) investigated the molecular mechanism and identified the downstream targets of DRß-H, and (3) comprehensively examined the expression pattern, underlying functions, and evident prognostic significance of NAP1L5 in BC by gathering the online information available. Results: DRß-H can inhibit the viability of the MCF-7/ADR and SUM-1315/ADR cancer cells in a dosage-dependent manner. NAP1L5 might be the main target of DRß-H in reversing ADR resistance. Its expression decreased in BC cells, and the more advanced the BC was, the lower the NAP1L5 expression was. Conclusion: DRß-H at nontoxic concentrations was related to ADR resistance in BC through its downstream target NAP1L5. NAP1L5 is potentially a preferable prognostic marker for BC.


Assuntos
Neoplasias da Mama , Saponinas , Humanos , Feminino , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Saponinas/farmacologia , Saponinas/uso terapêutico , Proteínas Nucleares/farmacologia , Proteínas Nucleares/uso terapêutico
8.
Int J Mol Sci ; 24(11)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37298247

RESUMO

Calcineurin, a key regulator of the calcium signaling pathway, is involved in calcium signal transduction and calcium ion homeostasis. Magnaporthe oryzae is a devastating filamentous phytopathogenic fungus in rice, yet little is known about the function of the calcium signaling system. Here, we identified a novel calcineurin regulatory-subunit-binding protein, MoCbp7, which is highly conserved in filamentous fungi and was found to localize in the cytoplasm. Phenotypic analysis of the MoCBP7 gene deletion mutant (ΔMocbp7) showed that MoCbp7 influenced the growth, conidiation, appressorium formation, invasive growth, and virulence of M. oryzae. Some calcium-signaling-related genes, such as YVC1, VCX1, and RCN1, are expressed in a calcineurin/MoCbp7-dependent manner. Furthermore, MoCbp7 synergizes with calcineurin to regulate endoplasmic reticulum homeostasis. Our research indicated that M. oryzae may have evolved a new calcium signaling regulatory network to adapt to its environment compared to the fungal model organism Saccharomyces cerevisiae.


Assuntos
Magnaporthe , Oryza , Virulência/genética , Calcineurina/genética , Calcineurina/metabolismo , Proteínas de Transporte/metabolismo , Sinalização do Cálcio , Cálcio/metabolismo , Magnaporthe/fisiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Oryza/metabolismo , Doenças das Plantas/microbiologia , Esporos Fúngicos
9.
Molecules ; 28(3)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36770726

RESUMO

Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.


Assuntos
Benzilisoquinolinas , Colite Ulcerativa , Colite , Animais , Camundongos , Humanos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Macrófagos , Colo/metabolismo , Benzilisoquinolinas/farmacologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Colite/metabolismo , Camundongos Endogâmicos C57BL
10.
Zhongguo Zhong Yao Za Zhi ; 48(6): 1597-1605, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-37005848

RESUMO

The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.


Assuntos
Isquemia Encefálica , Ferroptose , Traumatismo por Reperfusão , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Transdução de Sinais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Ciclo-Oxigenase 2/metabolismo , RNA Mensageiro , Infarto Cerebral , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Malondialdeído , Infarto da Artéria Cerebral Média
11.
Environ Microbiol ; 24(3): 1653-1671, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35229430

RESUMO

The development and pathogenicity of the fungus Magnaporthe oryzae, the causal agent of destructive rice blast disease, require it to perceive external environmental signals. Opy2, an overproduction-induced pheromone-resistant protein 2, is a crucial protein for sensing external signals in Saccharomyces cerevisiae. However, the biological functions of the homologue of Opy2 in M. oryzae are unclear. In this study, we identified that MoOPY2 is involved in fungal development, pathogenicity, and autophagy in M. oryzae. Deletion of MoOPY2 resulted in pleiotropic defects in hyphal growth, conidiation, germ tube extension, appressorium formation, appressorium turgor generation, and invasive growth, therefore leading to attenuated pathogenicity. Furthermore, MoOpy2 participates in the Osm1 MAPK pathway and the Mps1 MAPK pathway by interacting with the adaptor protein Mst50. The interaction sites of Mst50 and MoOpy2 colocalized with the autophagic marker protein MoAtg8 in the preautophagosomal structure sites (PAS). Notably, the ΔMoopy2 mutant caused cumulative MoAtg8 lipidation and rapid GFP-MoAtg8 degradation in response to nitrogen starvation, showing that MoOpy2 is involved in the negative regulation of autophagy activity. Taken together, our study revealed that MoOpy2 of M. oryzae plays an essential role in the orchestration of fungal development, appressorium penetration, autophagy and pathogenesis.


Assuntos
Magnaporthe , Oryza , Ascomicetos , Autofagia/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Magnaporthe/metabolismo , Oryza/microbiologia , Doenças das Plantas/microbiologia , Esporos Fúngicos/metabolismo , Virulência/genética
12.
J Sleep Res ; 31(6): e13562, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35166422

RESUMO

The beneficial effects of sleep for memory consolidation are assumed to rely on the reactivation of memories in conjunction with the coordinated interplay of sleep rhythms like slow oscillations and spindles. Specifically, slow oscillations are assumed to provide the temporal frame for spindles to occur in the slow oscillations up-states, enabling a redistribution of reactivated information within hippocampal-neocortical networks for long-term storage. Memory reactivation can also be triggered externally by presenting learning-associated cues (like odours or sounds) during sleep, but it is presently unclear whether there is an optimal time-window for the presentation of such cues in relation to the phase of the slow oscillations. In the present within-subject comparison, participants (n = 16) learnt word-pairs visually presented with auditory cues of the first syllable. These syllables were subsequently used for real-time cueing either in the up- or down-state of endogenous slow oscillations. Contrary to our hypothesis, we found differences in memory performance neither between up- and down-state cueing, nor between word-pairs that were cued versus uncued. In the up-state cueing condition, higher amounts of rapid eye movement sleep were associated with better memory for cued contents, whereas higher amounts of slow-wave sleep were associated with better memory for uncued contents. Evoked response analyses revealed signs of cue processing in both conditions. Interestingly, both up- and down-state cueing evoked a similar spindle response with the induced slow oscillations up-state at ~1000 ms post-cue. We speculate that our cueing procedure triggered generalised reactivation processes that facilitated the consolidation of both cued and uncued memories irrespective of the slow oscillation phase.


Assuntos
Consolidação da Memória , Sono de Ondas Lentas , Humanos , Consolidação da Memória/fisiologia , Sinais (Psicologia) , Eletroencefalografia/métodos , Sono/fisiologia , Sono de Ondas Lentas/fisiologia
13.
Int J Mol Sci ; 23(9)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35563048

RESUMO

Plant diseases caused by fungi are one of the major threats to global food security and understanding the interactions between fungi and plants is of great significance for plant disease control. The interaction between pathogenic fungi and plants is a complex process. From the perspective of pathogenic fungi, pathogenic fungi are involved in the regulation of pathogenicity by surface signal recognition proteins, MAPK signaling pathways, transcription factors, and pathogenic factors in the process of infecting plants. From the perspective of plant immunity, the signal pathway of immune response, the signal transduction pathway that induces plant immunity, and the function of plant cytoskeleton are the keys to studying plant resistance. In this review, we summarize the current research progress of fungi-plant interactions from multiple aspects and discuss the prospects and challenges of phytopathogenic fungi and their host interactions.


Assuntos
Fungos , Plantas , Doenças das Plantas/microbiologia , Imunidade Vegetal , Plantas/microbiologia , Fatores de Virulência
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(5): 904-910, 2022 Sep.
Artigo em Zh | MEDLINE | ID: mdl-36224695

RESUMO

Objective: To investigate the changes in social function impairment and quality of life and their predictive factors in patients with major depressive disorder (MDD) over the course of 1-year drug treatment. Methods: A total of 54 MDD patients were enrolled for the study. The 17-item Hamilton Rating Scale for Depression (HAMD-17, hereafter referred to simply as HAMD), Sheehan Disability Scale (SDS), and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) were used to evaluate depressive symptoms, social functioning, and quality of life, respectively, at baseline (0), as well as 1 month (1 m), 2 months (2 m), 3 months (3 m), 6 months (6 m), 9 months (9 m), and 12 months (12 m) after medication started. The symptoms and the recovery of social function at different time points was analyzed, and correlation analysis and regression analysis were done to explore the influencing factors of functional recovery. Results: Among the 54 MDD patients, 27 completed the 12-month follow-up, and 2 patients relapsed at 12 m. The total baseline score of SDS (SDS 0) in MDD patients was higher than that in healthy controls ( t=12.161, P<0.001), and the baseline score of Q-LES-Q-SF (Q-LES-Q-SF 0) was lower than that in the controls ( t=12.260, P<0.001). Comparison of the HAMD score, SDS total score and the factor scores, and Q-LES-Q-SF total scores of the MDD patients at different time points showed significant differences, presenting an F value of 65.987, 28.944, 23.589, 27.070 and 28.668, respectively (all P<0.001). HAMD 0 was negatively correlated with age. The HAMD score was positively correlated with SDS score of the same time point and negatively correlated with Q-LES-Q-SF score of the same time point. At 3 m, the change in HAMD score (HAMD 3 m-0) was positively correlated with the change in SDS score (SDS 3 m-0) and negatively correlated with the change in Q-LES-Q-SF score (Q-LES-Q 3 m-0). At 12 m, the change in HAMD score (HAMD 12 m-0) was positively correlated with the change in SDS score (SDS 12 m-0) and negatively correlated with the change in Q-LES-Q-SF score (Q-LES-Q 12 m-0). Regression analysis revealed that SDS 0 and Q-LES-Q 0 could be used to predict SDS 3 m-0, R 2=0.391, while SDS 0 and full-time employment status could be used to predict SDS 12 m-0, R 2=0.640. Q-LES-Q 0 could be used to predict Q-LES-Q 3 m-0, R 2=0.294, while Q-LES-Q 0 and full-time employment status could be used to predict Q-LES-Q 12 m-0, R 2=0.591. Conclusion: Long-term regular medication can improve social dysfunction in patients with MDD and symptom relief is the basis for improvement of social function level and quality of life, while increasing employment saturability to some extent may help improve the long-term social function and quality of life.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Qualidade de Vida , Inquéritos e Questionários
15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 22-27, 2021 Jan.
Artigo em Zh | MEDLINE | ID: mdl-33474884

RESUMO

Stress can improve an individual's ability to adapt to environmental changes. However, excessive stress can induce stress-related mental disorders, including anxiety disorder, depression disorder and post-traumatic stress disorder (PTSD). Stress can regulate the level of hormones and immune inflammation in the body through the brain network, neural circuits, hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, thereby causing the occurrence of mental disorders. In addition, stress can mediate the occurrence of mental disorders by regulating molecular changes in the level of genes, transcription, protein and metabolism, etc. Studies have shown that the brain-gut axis also plays an important role in the pathogenesis of stress-related mental disorders. However, the pathophysiological mechanism of stress-related mental disorders remains unclear. Besides, studies have also shown that the onset of stress-related mental disorders is closely associated with the individual's physiological and psychological qualities,which has a cross-talk with other mental and physical diseases as well. Therefore, it is important to study individual premorbid diathesis clinical, and to conduct clinical medical, basic medical, and psychological studies of the different stages of the disease, so as to obtain further understanding of the pathogenesis of stress-related mental disorders.


Assuntos
Sistema Hipotálamo-Hipofisário , Transtornos de Estresse Pós-Traumáticos , Transtornos de Ansiedade/etiologia , Humanos , Sistema Hipófise-Suprarrenal , Transtornos de Estresse Pós-Traumáticos/etiologia , Estresse Psicológico/complicações
16.
Mikrochim Acta ; 187(6): 333, 2020 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-32415377

RESUMO

A low-field nuclear magnetic resonance (LF-NMR) DNA-hydrogel (LNDH) nanoprobe was designed for bisphenol A (BPA) determination. It consists of Fe3O4 superparamagnetic iron oxide nanoparticles (SPIONs) and a DNA-hydrogel technology. Fe3O4 SPIONs were encapsulated in the DNA-hydrogel to form an aggregated state. After adding BPA, the gel system transformed into a sol gel due to the target-aptamer specific binding. The coated gathered particles dispersed and thus, the relaxation time T2 declined. The LNDH nanoprobe was developed to realize a simple, sensitive, and effective BPA determination method without repeated magnetic separation steps. Under the optimal experimental conditions, the determination range of the LNDH biosensor was 10-2~102 ng mL-1 and the limit of determination was 0.07 ng mL-1. The LNDH nanoprobe was applied to two kinds of water samples (tap water and bottled water). The recovery ranged from 87.85 to approximately 97.87%. This strategy offered a new method to detect BPA by LF-NMR. It is also expected to be applicable in related fields of food safety determination, environmental monitoring, and clinical diagnosis. Graphical abstract Schematic presentation of LNDH biosensor. Acrydite-modified ssDNA was copolymerized with acrylamide to form linear conjugates PS-A/B, adding aptamer and SPIONs to form DNA-hydrogel. When aptamer captured the target, the hydrogel was destroyed to disperse the coated SPIONs. T2 relaxation time declined.


Assuntos
Compostos Benzidrílicos/análise , DNA de Cadeia Simples/química , Água Potável/química , Hidrogéis/química , Nanopartículas de Magnetita/química , Fenóis/análise , Poluentes Químicos da Água/análise , Aptâmeros de Nucleotídeos/química , Compostos Benzidrílicos/química , Técnicas Biossensoriais , Limite de Detecção , Espectroscopia de Ressonância Magnética , Fenóis/química
17.
J Neurosci ; 37(18): 4717-4734, 2017 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-28381592

RESUMO

The lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) of the primate play distinctive roles in the mediation of complex cognitive tasks. Compared with the LPFC, integration of information by the ACC can span longer timescales and requires stronger engagement of inhibitory processes. Here, we reveal the synaptic mechanism likely to underlie these differences using in vitro patch-clamp recordings of synaptic events and multiscale imaging of synaptic markers in rhesus monkeys. Although excitatory synaptic signaling does not differ, the level of synaptic inhibition is much higher in ACC than LPFC layer 3 pyramidal neurons, with a significantly higher frequency (∼6×) and longer duration of inhibitory synaptic currents. The number of inhibitory synapses and the ratio of cholecystokinin to parvalbumin-positive inhibitory inputs are also significantly higher in ACC compared with LPFC neurons. Therefore, inhibition is functionally and structurally more robust and diverse in ACC than in LPFC, resulting in a lower excitatory: inhibitory ratio and a greater dynamic range for signal integration and network oscillation by the ACC. These differences in inhibitory circuitry likely underlie the distinctive network dynamics in ACC and LPC during normal and pathological brain states.SIGNIFICANCE STATEMENT The lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) play temporally distinct roles during the execution of cognitive tasks (rapid working memory during ongoing tasks and long-term memory to guide future action, respectively). Compared with LPFC-mediated tasks, ACC-mediated tasks can span longer timescales and require stronger engagement of inhibition. This study shows that inhibitory signaling is much more robust and diverse in the ACC than in the LPFC. Therefore, there is a lower excitatory: inhibitory synaptic ratio and a greater dynamic range for signal integration and oscillatory behavior in the ACC. These significant differences in inhibitory synaptic transmission form an important basis for the differential timing of cognitive processing by the LPFC and ACC in normal and pathological brain states.


Assuntos
Giro do Cíngulo/fisiologia , Rede Nervosa/fisiologia , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Córtex Pré-Frontal/fisiologia , Transmissão Sináptica/fisiologia , Animais , Feminino , Giro do Cíngulo/citologia , Macaca mulatta , Masculino , Rede Nervosa/citologia , Córtex Pré-Frontal/citologia
18.
J Org Chem ; 83(11): 5931-5946, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29733638

RESUMO

A chemodivergent reaction of 2-indolylmethanols with tryptophols has been established via an interrupted Nazarov-type cyclization in the presence of Brønsted acid, leading to the efficient synthesis of two series of cyclopenta[ b]indole derivatives in a broad substrate scope with high yields and excellent diastereoselectivities (42 examples, up to 99% yield, all >95:5 dr). It was found that the presence or absence of molecular sieves played an important role in controlling the chemoselectivity of the reaction. In the presence of 3 Å molecular sieves, tryptophol would utilize the nucleophilicity of its nitrogen atom to form a new C-N bond, while, in the absence of molecular sieves, tryptophol would utilize the nucleophilicity of its C2-position to generate a new C-C bond. Therefore, this reaction will provide a good example for additive-controlled chemoselectivity. In addition, this approach not only provides a useful strategy for the synthesis of structurally diversified cyclopenta[ b]indoles but also demonstrates the practicability of 2-indolylmethanols in organic synthesis.

19.
Child Dev ; 89(5): 1720-1734, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28594100

RESUMO

Abilities to encode and remember events in their spatiotemporal context (episodic memory) rely on brain regions that mature late during childhood and are supported by sleep. We compared the temporal dynamics of episodic memory formation and the role of sleep in this process between 62 children (8-12 years) and 57 adults (18-37 years). Subjects recalled "what-where-when" memories after a short 1-hr retention interval or after a long 10.5-hr interval containing either nocturnal sleep or daytime wakefulness. Although children showed diminished recall of episodes after 1 hr, possibly resulting from inferior encoding, unlike adults, they showed no further decrease in recall after 10.5 hr. In both age groups, episodic memory benefitted from sleep. However, children's more effective offline retention was unrelated to sleep.


Assuntos
Consolidação da Memória , Memória Episódica , Rememoração Mental , Adulto , Criança , Feminino , Humanos , Masculino , Memória de Longo Prazo , Sono , Fatores de Tempo , Adulto Jovem
20.
Molecules ; 22(10)2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-28937640

RESUMO

A series of novel sulfonylurea benzothiazolines was designed by splicing active groups and bioisosterism. A solvent-free synthetic route was developed for the sulfonylurea benzothiazoline derivatives via the cyclization and carbamylation. All compounds were characterized by IR, ¹H-NMR, 13C-NMR, HRMS. The biological activity tests indicated the compounds could protect maize against the injury caused by chlorsulfuron to some extent. The molecular docking result showed that the new compound competed with chlorsulfuron to bind with the herbicide target enzyme active site to attain detoxification.


Assuntos
Benzotiazóis/química , Compostos de Sulfonilureia/química , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Solventes/química , Sulfonamidas/química , Triazinas/química
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