Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
1.
Nanotechnology ; 35(30)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38636478

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid plaques in the brain. The toxicity of amyloid to neuronal cell surfaces arises from interactions between small intermediate aggregates, namely amyloid oligomers, and the cell membrane. The nature of these interactions changes with age and disease progression. In our previous work, we demonstrated that both membrane composition and nanoscale structure play crucial roles in amyloid toxicity, and that membrane models mimicking healthy neuron were less affected by amyloid than model membranes mimicking AD neuronal membranes. This understanding introduces the possibility of modifying membrane properties with membrane-active molecules, such as melatonin, to protect them from amyloid-induced damage. In this study, we employed atomic force microscopy and localized surface plasmon resonance to investigate the protective effects of melatonin. We utilized synthetic lipid membranes that mimic the neuronal cellular membrane at various stages of AD and explored their interactions with amyloid-ß(1-42) in the presence of melatonin. Our findings reveal that the early diseased membrane model is particularly vulnerable to amyloid binding and subsequent damage. However, melatonin exerts its most potent protective effect on this early-stage membrane. These results suggest that melatonin could act at the membrane level to alleviate amyloid toxicity, offering the most protection during the initial stages of AD.


Assuntos
Peptídeos beta-Amiloides , Melatonina , Microscopia de Força Atômica , Ressonância de Plasmônio de Superfície , Melatonina/farmacologia , Melatonina/química , Microscopia de Força Atômica/métodos , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Bicamadas Lipídicas/química , Doença de Alzheimer/metabolismo , Humanos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/química
2.
Mol Immunol ; 169: 86-98, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552285

RESUMO

Acute liver failure (ALF) is a life-threatening disease with high mortality. Given excessive inflammation is one of the major pathogenesis of ALF, candidates targeting inflammation could be beneficial in the condition. Now the effect of hyperactivated succinate dehydrogenase (SDH) on promoting inflammation in lipopolysaccharide (LPS)-treated macrophages has been studied. However, its role and mechanism in ALF is not well understood. Here intraperitoneal injection of D-galactosamine and LPS was conducted in male C57BL/6 J mice to induce the ALF model. Dimethyl malonate (DMM), which inhibited SDH activity, was injected intraperitoneally 30 min before ALF induction. Macrophage pyroptosis was induced by LPS plus adenosine triphosphate (ATP). Pyroptosis-related molecules and proteins including GSDMD oligomer were examined by ELISA and western blot techniques, respectively. ROS production was assessed by fluorescence staining. The study demonstrated SDH activity was increased in liver macrophages from ALF mice. Importantly, DMM administration inhibited ROS, IL-1ß, and pyroptosis-associated proteins levels (NLRP3, cleaved caspase-1, GSDMD-N, and GSDMD oligomers) both in the ALF model and in macrophages stimulated with LPS plus ATP. In vitro, ROS promoted pyroptosis by facilitating GSDMD oligomerization. Additionally, when ROS levels were increased through the addition of H2O2 to the DMM group, the levels of GSDMD oligomers were reverted. In conclusion, SDH hyperactivation promotes macrophage pyroptosis by ROS-mediated GSDMD oligomerization, suggesting that targeting this pathway holds promise as a strategy for treating ALF and other inflammatory diseases.


Assuntos
Falência Hepática Aguda , Animais , Masculino , Camundongos , Trifosfato de Adenosina/metabolismo , Linhagem Celular , Peróxido de Hidrogênio/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Falência Hepática Aguda/induzido quimicamente , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Espécies Reativas de Oxigênio/metabolismo , Succinato Desidrogenase/metabolismo , Succinato Desidrogenase/farmacologia
3.
Cell Death Dis ; 15(1): 102, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291031

RESUMO

Early metastasis is the primary factor in the very poor prognosis of pancreatic ductal adenocarcinoma (PDAC), with liver metastasis being the most common form of distant metastasis in PDAC. To investigate the mechanism of PDAC liver metastasis, we found that PDAC cells can promote the formation of pre-metastatic niches (PMNs) through exosomes to facilitate liver metastasis in the early stage. In our study, hepatic stellate cells (HSCs) were treated with PDAC-derived exosomes (PDAC-exo), and the activation of HSCs was detected. A novel transfer RNA-derived fragment, the tRF-GluCTC-0005 was obtained by small RNA sequencing from serum exosomes of PDAC patients. Bioinformatics analysis and RNA pull-down assays revealed the interaction between WDR1 and tRF-GluCTC-0005. A KPC transgenic mouse model and an AAV-mediated sh-WDR1 mouse model were used to detect the mechanism of liver metastasis in vivo. Finally, the dual luciferase reporter assay, protein mutation truncation assay, Co-IP assay, and flow cytometry assay were used to explore the molecular mechanism in HSCs activation and PMNs formation. We found that the tRF-GluCTC-0005 in exosomes binds to the 3' untranslated region of the mRNA of the WDRl in HSCs and increases mRNA stability. The N-terminals of WDR1 bind to the YAP protein directly, inhibit YAP phosphorylation, and promote the expression of YAP transcription factors. The tRF-GluCTC-0005 in PDAC-exo significantly recruits myeloid-derived suppressor cells (MDSCs) in the liver, creating a PMNs immunosuppressive microenvironment and further advancing liver metastasis from PDAC. Our results suggest that the key of PDAC liver metastasis is the activation of HSCs through upregulation of WDR1 by tRF-GluCTC-0005 in exosomes, which mediates the infiltration of MDSCs to form PMNs.


Assuntos
Carcinoma Ductal Pancreático , Exossomos , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Células Estreladas do Fígado/metabolismo , Exossomos/metabolismo , Linhagem Celular Tumoral , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias Hepáticas/patologia , RNA de Transferência/metabolismo , Microambiente Tumoral
4.
Cancer Nurs ; 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206596

RESUMO

BACKGROUND: Patients with advanced cancer may experience symptom clusters during treatment (eg, fatigue, pain, sleep disturbance, depression). Understanding the characteristics and factors associated with symptom cluster classes among this patient population is essential for effective symptom management. OBJECTIVE: The aims of this study were to identify symptom cluster (fatigue-pain-sleep disturbance-depression) classes and explore influencing factors in patients with advanced cancer during the treatment. METHODS: A cross-sectional survey was conducted in an oncology department of a tertiary hospital in China from September 2020 to March 2021. Cancer patients (stage III/IV) 18 years or older completed the questionnaires on pain, fatigue, sleep disturbance, depression, physical activity, and exercise self-efficacy. Latent class analysis and multinomial logistic regression were used. RESULTS: Three hundred sixty-five patients who were male (65.2%) and younger than 60 years (59.5%) completed questionnaires. Three symptom cluster classes were identified: class 1 ("low symptom burden" class), class 2 ("fatigue-insomnia" class), and class 3 ("high symptom burden" class), with a percentage of 54.5%, 38.6%, and 6.8%, respectively. The quality-of-life score, introversion/extroversion, economic burden, Karnofsky Performance Status, albumin level, and exercise self-efficacy were significantly different among the 3 classes (P < .05). CONCLUSION: Patients with advanced cancer were classified into 3 distinct classes, with class 1 having the best function. Results from this study reveal that Karnofsky Performance Status, albumin level, and exercise self-efficacy were significant factors for the latent classes of symptom cluster. IMPLICATIONS FOR PRACTICE: Exercise self-efficacy is important for personalized interventions and improving symptom management efficiency.

5.
Plants (Basel) ; 12(22)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-38005706

RESUMO

Abscisic acid (ABA) is an important stress hormone that affects plants' tolerance to stress. Changes in the content of abscisic can have an impact on plant responses to abiotic stress. The abscisic acid aldehyde oxidase (AAO) plays a crucial role in the final step in the synthesis of abscisic acid; therefore, understanding the function of the AAO gene family is of great significance for insight into plants' response to abiotic stresses. In this study, Solanum tuberosum AAO (StAAO) members were exhaustively explored using genome databases, and nine StAAOs were identified. Chromosomal location analysis indicated that StAAO genes mapped to 4 of the 14 potato chromosomes. Further analyses of gene structure and motif composition showed that members of the specific StAAO subfamily showed relatively conserved characteristics. Phylogenetic relationship analysis indicated that StAAOs proteins were divided into three major clades. Promoter analysis showed that most StAAO promoters contained cis-elements related to abiotic stress response and plant hormones. The results of tissue-specific expression analysis indicated that StAAO4 was predominantly expressed in the roots. Analysis of transcriptome data revealed that StAAO2/4/6 genes responded significantly to drought treatments. Moreover, further qRT-PCR analysis results indicated that StAAO2/4/6 not only significantly responded to drought stress but also to various phytohormone (ABA, SA, and MeJA) and abiotic stresses (salt and low temperature), albeit with different expression patterns. In summary, our study provides comprehensive insights into the sequence characteristics, structural properties, evolutionary relationships, and expression patterns of the StAAO gene family. These findings lay the foundation for a deeper understanding of the StAAO gene family and offer a potential genetic resource for breeding drought-resistant potato varieties.

6.
Front Microbiol ; 14: 1267746, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954244

RESUMO

Introduction: Soil microorganisms are an important component of soil ecosystems with an indispensable role in forest ecosystems. We analyzed the soil microbial diversity in birch secondary forest formed by natural restoration or artificial reconstruction after interference by burning, clear cutting, and gradient cutting, and the Betula platyphylla Suk undisturbed forest in the Greater Khingan Mountains in China. Methods: Illumina high-throughput sequencing technology was used to analyze the characteristics of the soil microbial community during the restoration process of birch secondary forest caused by the different types of interference. The relationships between bacteria and fungi were analyzed. The gene functions of the soil bacterial community and the ecological functions of soil fungi were predicted using PICRUSt and FunGuild, respectively. Results: At the phylum level, the species and quantity of bacteria were more abundant than that of fungi. At the genus level, no obvious differences in the abundance of bacteria were observed; there were obvious differences in the abundance of fungi. Among the eight sample plots, the artificial larch forest belt had the highest bacterial and fungal alpha diversity, which was slightly higher than undisturbed forest, while the other sample plots were significantly lower. Gradual cutting pure birch forest bacteria and fungi had the highest beta diversity, and artificial larch forest belt bacteria and heavy burn sample plot fungi had the lowest beta diversity. Samples from the cutting and burning sample plots were significantly different from the undisturbed forest at the phylum level of Acidobacteriae, Acidimicrobiia, Mortierellomycetes and Sordariomycetes. We found statistical differences in biomarkers between bacterial and fungal communities in undisturbed forest and artificial larch forest belt and burn sample plots. PICRUSt prediction and FunGuild prediction showed that soil bacterial and fungal communities were rich in gene and ecological functions, respectively. In the microbial network, the stability or anti-interference performance of the fungal community was higher than that of bacteria. Conclusion: Our data reveal the characteristics of the soil microbial community during the restoration process of Betula platyphylla Suk secondary forest under different types of disturbance, which is of great significance for understanding the role of soil microorganisms in the forest ecological cycle.

7.
Exp Neurol ; 370: 114549, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37774765

RESUMO

Single therapeutic interventions have not yet been successful in restoring function after spinal cord injury. Accordingly, combinatorial interventions targeting multiple factors may hold greater promise for achieving maximal functional recovery. In this study, we applied a combinatorial approach of chronic chemogenetic neuronal activation and physical exercise including treadmill running and forelimb training tasks to promote functional recovery. In a mouse model of cervical (C5) dorsal hemisection of the spinal cord, which transects almost all descending corticospinal tract axons, combining selective activation of corticospinal motoneurons (CMNs) by intersectional chemogenetics with physical exercise significantly promoted functional recovery evaluated by the grid walking test, grid hanging test, rotarod test, and single pellet-reaching tasks. Electromyography and histological analysis showed increased activation of forelimb muscles via chemogenetic stimuli, and a greater density of vGlut1+ innervation in spinal cord grey matter rostral to the injury, suggesting enhanced neuroplasticity and connectivity. Combined therapy also enhanced activation of mTOR signaling and reduced apoptosis in spinal motoneurons, Counts revealed increased numbers of detectable choline acetyltransferase-positive motoneurons in the ventral horn. Taken together, the findings from this study validate a novel combinatorial approach to enhance motor function after spinal cord injury.


Assuntos
Traumatismos da Medula Espinal , Animais , Camundongos , Neurônios Motores/fisiologia , Medula Espinal/patologia , Tratos Piramidais/patologia , Axônios/patologia , Exercício Físico , Recuperação de Função Fisiológica/fisiologia
8.
Food Funct ; 14(2): 990-1002, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36545693

RESUMO

In today's society, obesity is becoming increasingly serious, and controlling food intake and maintaining weight balance have become increasingly important. Here, we found that a stearic acid diet can increase food intake without causing obesity in mice compared with an oleic acid diet. Stearic acid increases food intake in mice by reducing serum leptin and increasing NPY neuronal excitability through the JAK2/STAT3 pathway. The impaired anorexic effect of leptin is probably due to repressive cholesterol-oxysterol-LXR-α/SREBP-1c-mediated leptin expression in mouse iWAT. At the same time, we found that stearic acid was not only poorly absorbed by itself in the small intestine but also reduced the entire absorption system of the small intestine. In conclusion, we have proven that a stearic acid diet can increase food intake in mice and avoid obesity, but whether a stearic acid diet could cause adverse reactions in the body remains to be studied.


Assuntos
Leptina , Ácido Oleico , Camundongos , Animais , Dieta , Obesidade/metabolismo , Ingestão de Alimentos , Peso Corporal
9.
Front Pediatr ; 10: 1032659, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568422

RESUMO

Background: Deafness is the most common sensory defect in humans worldwide. Approximately 50% of cases are attributed to genetic factors, and about 70% are non-syndromic hearing loss (NSHL). Objectives: To identify clinically relevant gene variants associated with NSHL in a Chinese family using trio-based whole-exome sequencing (WES). Materials and methods: WES was performed on the 18-month-old female proband, and her parents. Gene variants specific to the family were identified by bioinformatics analysis and evaluated for their relevance to NSHL. We verified the novel variant in this family by the next-generation sequencing.In order to elucidate the frameshift mutation of TMPRSS3 in a Chinese family, we used the Mass spectrometry to detect the gene from 1,010 healthy subjects. Results: We identified a novel homozygous deletion (c.51delA) in exon 2 of the type II transmembrane serine protease 3 gene TMPRSS3, which resulted in a frameshift mutation just before the protein transmembrane domain (p.Q17fs). The deletion was present in the proband and her father, but not in her mother and the healthy controls. We also found mutations with potential relevance to hearing loss in DCAF17, which encodes a protein of unknown function (c. T555A: p.H185Q), and ZNF276, which encodes zinc finger protein 276 (c.1350-2A > G). Conclusions and significance: We shown a novel frameshift mutation in TMPRSS3 associated with autosomal recessive NSHL in a Han Chinese family.

10.
Front Genet ; 13: 1034832, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406123

RESUMO

We previously screened 6 differentially expressed miRNAs in ovarian tissues of 4-vinylcyclohexene diepoxide (VCD)-treated premature ovarian failure (POF) model in SD rats, including miRNA-190a-5p, miRNA-98-5p, miRNA-29a-3p, miRNA-144-5p, miRNA-27b-3p, miRNA-151-5p. In this study, to investigate the mechanisms causing the onset of POF, we first identified miRNAs with earlier differential expression at consecutive time points in the VCD-treated rat POF model and explored the mechanisms by which the target miRNAs promote POF. The SD rats were injected with VCD for 15 days to induce POF. Additionally, we collected rat blood and ovaries at the same time every day for 15 consecutive days, and luteinizing hormone (LH), follicle-stimulating hormone (FSH), Anti-Mullerian hormone (AMH), and estradiol (E2) serum levels were detected by ELISA. Six miRNAs expression were measured in rat ovaries by qRT-PCR. Dual-luciferase reporter gene assays were employed to predict and verify the target gene (PHLPP1) of target miRNAs (miRNA-190a-5p). Western blot was examined to detect the expression levels of PHLPP1, AKT, p-AKT, FOXO3a, p-FOXO3a, and LHR proteins on the target gene PHLPP1 and its participation in the primordial follicular hyperactivation-related pathways (AKT-FOXO3a and AKT-LH/LHR). During the VCD modeling POF rat ovaries, miRNA-190a-5p was the first to show significant differential expression, i.e., 6th of VCD treating, and PHLPP1 was verified to be a direct downstream target of it. Starting from the 6th of VCD treatment, the more significant the up-regulation trend of miRNA-190a-5p expression, the more obvious the down-regulation trend of PHLPP1 and LHR mRNA and protein expression, accompanied by the more severe phosphorylation of AKT and FOXO3a proteins, thus continuously over-activating the rat primordial follicle to promote the development of POF. In conclusion, miRNA-190a-5p may become a potential biomarker for early screening of POF, and it can continuously activate primordial follicles in rats by targeting the expression of PHLPP1 and key proteins in the AKT-FOXO3a and AKT-LH/LHR pathways.

11.
Chemosphere ; 298: 134290, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35278446

RESUMO

Working fluid preparation using treated drilling wastewater is of great potential for drilling wastewater reuse, especially in water-deficient and ecologically fragile areas, which require low levels of organic matter and suspended solids (SS). This study established the dissolved ozone flotation (DOF) process as the advanced treatment process to replace the original electrocatalytic system (ECS) which exhibited low organic and suspended solids removal efficiency. Higher and more stable organic matter, suspended solids and turbidity removal efficiency were obtained for the DOF process. Consequently, the lower fouling potential and higher water production rate of treated water from DOF process was observed for the following reverse osmosis (RO) system. In addition, brine drilling fluids can be successfully prepared using DOF effluent directly, which exhibited promising practical implications in the advanced drilling wastewater treatment. Based on organic matter fractionation and redundancy analysis (RDA), the hydrophobic acid (HOA), hydrophobic neutral (HON) and hydrophilic fraction (HI) contents significantly impacted brine drilling fluid preparation. Based on X-ray photoelectron spectroscopy (XPS) analysis, the aromatic carbon species in the HOA, HON and HI fractions were found to be the critical factors deteriorating the brine drilling fluid preparation. However, oxygen-containing groups played a positive role. The favorable brine drilling fluid preparation performance using DOF effluent directly can be ascribed to the removal of HOA, HON and HI fractions and enhanced generation of oxygen-containing groups in ozone flotation zone.


Assuntos
Ozônio , Poluentes Químicos da Água , Purificação da Água , Ácidos , Campos de Petróleo e Gás , Ozônio/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Água/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos
12.
Food Addit Contam Part B Surveill ; 15(1): 38-41, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34714220

RESUMO

Selenium-rich rice samples of 52 brands were bought from supermarkets on line in China and analysed for Se with ICP-MS. The Se concentration of Se-rich rice in China ranged from 0.012 ± 0.001 to 0.558 ± 0.057 mg/kg with an average of 0.090 ± 0.092 mg/kg. Rice samples with Se concentrations below 0.04 mg/kg accounted for 36.5% of the total samples. Se concentrations between 0.04 and 0.3 mg/kg accounted for 61.6%. Taking the upper tolerable limit of 400 µg/d as the risk standard, the risk of selenium intake by selenium-rich rice was low and the risk index was far less than 100%. With the upper intake limit of 100 µg/d and the adequate intake of 70 µg/d as the risk standard, the maximum intake risk index was higher than 100%, indicating a certain risk in the consumption of selenium-rich rice.


Assuntos
Oryza , Selênio , China , Contaminação de Alimentos/análise , Estado Nutricional , Medição de Risco , Selênio/análise
13.
Front Med (Lausanne) ; 8: 769132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869485

RESUMO

Purpose: To explore the therapeutic effect of a dietary supplement on dry eye with meibomian gland dysfunction (MGD). Methods: Sixty patients with MGD-related dry eye were included in this prospective and randomized, placebo-controlled study. All the subjects were treated with eye hot compress, artificial tears, and antibiotic ointment. After that, the patients received dietary supplementary or placebo daily for 12 weeks. The dry eye signs, function of MG, and visual quality of the patients were assessed at 4, 8, and 12 weeks after the treatment. Results: Twelve weeks after the treatment, patients who received dietary supplement had a significantly better improvement of dry eye symptoms, in terms of ocular surface diseases index and tear breaking-up time (TBUT), than those who received placebo (P < 0.05). The functions of MG, in terms of meibum quality and MG exclusion and MG obstruction scores, were significantly improved in both dietary supplement and placebo groups (P < 0.05). Patients who received dietary supplement had a significantly better improvement in the MG structure, in terms of acinar diameter and acinar density, than those who received placebo (P < 0.05). The number of inflammatory cells near MG was significantly lower in the dietary supplement group when compared with the placebo group (P < 0.05). The objective visual quality was significantly improved in the dietary supplement group, but not in the placebo group (P < 0.05). Conclusion: The dietary supplement can effectively improve the symptoms and signs of MGD-related dry eye, reduce the inflammatory reaction of MG, restore the gland structure, and indirectly improve the visual quality.

14.
Org Lett ; 23(18): 7028-7032, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34459610

RESUMO

A versatile copper-catalyzed [3 + 1 + 1] annulation of oximes and isocyanates with AgNO3 is described. In this conversion, AgNO3 and isocyanates instead of conventional azide or diazonium reagents were used as the nitrogen source. This three-component transformation was achieved by cleaving N-O/C-H/C-N bonds and building C═N/N-N bonds, which provides a strategy to prepare N-2-aryl-1,2,3-triazoles with a good substrate and functional compatibility.

16.
Org Biomol Chem ; 19(21): 4783-4787, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-33982036

RESUMO

A simple and practical method for α-ketoamide synthesis via a decarboxylative strategy of isocyanates with α-oxocarboxylic acids is described. The reaction proceeds at room temperature under mild conditions without an oxidant or an additive, showing good substrate scope and functional compatibility. Moreover, the applicability of this method was further demonstrated by the synthesis of various bioactive molecules and different application examples through a two-step one-pot operation.

17.
Trends Neurosci ; 44(5): 366-377, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33568331

RESUMO

Dopamine (DA) neurons of the dorsal raphe nucleus (DRN) were traditionally viewed as an extension of the ventral tegmental area (VTA) DA population. While the VTA DA population is known to play important roles in reward processing, emerging evidence now supports the view that DRN DA neurons are a specialized midbrain DA subsystem that performs distinct functions in parallel to the VTA DA population. Recent studies have shed new light on the roles of DRN DA neurons in encoding incentive salience and in regulating memory expression and arousal. Here, we review recent findings using mouse models about the physiology and behavioral functions of DRN DA neurons, highlight the engagement of DRN DA neurons and their upstream circuits in opioid addiction, and discuss emerging lines of investigation that reveal multifaceted heterogeneity among DRN DA neurons.


Assuntos
Dopamina , Área Tegmentar Ventral , Animais , Nível de Alerta , Neurônios Dopaminérgicos , Camundongos , Recompensa
18.
Neuron ; 106(3): 498-514.e8, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32145184

RESUMO

The brain dopamine (DA) system participates in forming and expressing memory. Despite a well-established role of DA neurons in the ventral tegmental area in memory formation, the exact DA circuits that control memory expression remain unclear. Here, we show that DA neurons in the dorsal raphe nucleus (DRN) and their medulla input control the expression of incentive memory. DRN DA neurons are activated by both rewarding and aversive stimuli in a learning-dependent manner and exhibit elevated activity during memory recall. Disrupting their physiological activity or DA synthesis blocks the expression of natural appetitive and aversive memories as well as drug memories associated with opioids. Moreover, a glutamatergic pathway from the lateral parabrachial nucleus to the DRN selectively regulates the expression of reward memories associated with opioids or foods. Our study reveals a specialized DA subsystem important for memory expression and suggests new targets for interventions against opioid addiction.


Assuntos
Neurônios Dopaminérgicos/fisiologia , Memória , Núcleos da Rafe/fisiologia , Recompensa , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Feminino , Ácido Glutâmico/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfina/farmacologia , Entorpecentes/farmacologia , Núcleos da Rafe/citologia , Núcleos da Rafe/metabolismo
19.
Brain Behav Immun ; 85: 120-127, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31255682

RESUMO

Evidence shows that gut microbiota may play important roles in schizophrenia pathogenesis via the "gut-brain" axis, but the mechanisms remain unclear. Here, eighty-four patients with schizophrenia and 84 sex- and age-matched healthy controls were enrolled. Shotgun metagenomic sequencing and 16S rRNA sequencing were performed, and the gut microbiota-associated epitopes (MEs) were predicted, which, together with IgA content, were used to determine the gut microbiota composition associated with gut immune status. Patients with schizophrenia had significantly reduced gut microbiota richnesses compared with those of the healthy controls, and the gut microbiota compositions clearly distinguished the patients with schizophrenia from the healthy controls. Based on two-stage metagenomic-wide association studies, nineteen gut microbiota taxonomies were associated with schizophrenia, and the microbial dysbiosis (MD) index was calculated based on the abundance of differential taxonomies. We found that MD index was positively correlated with MEs diversity and gut IgA levels, and negatively correlated with gut microbiota richness. Glutamate synthase (GOGAT) was more active in the guts of patients with schizophrenia than in those of healthy controls, and high GOGAT activity was associated with altered gut microbiota taxonomies associated with gut IgA levels. Our results may imply a role of the microbiome in the etiology of schizophrenia and contribute to the development of microbiome targeted interventions for schizophrenia.


Assuntos
Microbioma Gastrointestinal , Esquizofrenia , Disbiose , Humanos , Imunidade nas Mucosas , RNA Ribossômico 16S/genética
20.
Medicine (Baltimore) ; 97(51): e13553, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572456

RESUMO

BACKGROUND: Diagnosing schizophrenia is primarily based on the presentation of defined signs and symptoms, none of which is pathognomonic for this group of syndromes. However, few significant genome-wide associations between schizophrenia and individual have detected. Protein profiling of candidate serum biomarkers in schizophrenia is therefore an area of great interest. METHODS: In the present study, we used a combination of 7% polyethylene glycol (PEG) enrichment of immune complexes and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to separate abnormal band, then analyse the band with liquid chromatography mass spectrometry (LC-MS). RESULTS: There is a special 150-kD electrophoretic band in patients with schizophrenia, bipolar disorder, or depression relative to healthy controls (each 30 samples). Analysis of the band using LC-MS resulted in the identification of 11 serum proteins whose abundance was altered between patients and controls. Among them, 8 proteins (CFH, CFB, cDNA FLJ75416, zinc finger protein 729, isoform 2 of nidogen-1, diaphanous-1, cDNA FLJ77762, and cDNA FLJ58411) were up regulated, while one protein (isoform 1 of collagen alpha-1 (II) was down regulated in patients with schizophrenia, but only zinc finger protein 729 has statistics significance (P < .05). No differences were noted with regard to thrombospondin-1 or collagen alpha-2 (I) among the 3 groups. These proteins take part in several biological functions such as focal adhesion, complement cascades, ECM-receptor interaction, and Staphylococcus aureus infection. CONCLUSIONS: The 150-kD electrophoretic band or zinc finger protein 729 may become biomarkers in patients with schizophrenia. In the future increasing sample size and function research of zinc finger protein 729 should be executed continuously.


Assuntos
Cromatografia Líquida , Eletroforese em Gel de Poliacrilamida , Espectrometria de Massas , Proteínas/metabolismo , Esquizofrenia/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...