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1.
Int J Biol Macromol ; 263(Pt 2): 130245, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38367779

RESUMEN

The dynamic adhesion between cells and their extracellular matrix is essential for the development and function of organs. During insect wing development, two epithelial sheets contact each other at their basal sites through the interaction of ßPS integrins with the extracellular matrix. We report that Osiris17 contributes to the maintenance of ßPS integrins localization and function in developing wing of Drosophila and locust. In flies with reduced Osiris17 expression the epithelia sheets fail to maintain the integrity of basal cytoplasmic junctional bridges and basal adhesion. In contrast to the continuous basal integrin localization in control wings, this localization is disrupted during late stages of wing development in Osiris17 depleted flies. In addition, the subcellular localization revealed that Osiris17 co-localizes with the endosomal markers Rab5 and Rab11. This observation suggests an involvement of Osiris17 in endosomal recycling of integrins. Indeed, Osiris17 depletion reduced the numbers of Rab5 and Rab11 positive endosomes. Moreover, overexpression of Osiris17 increased co-localization of Rab5 and ßPS integrins and partially rescued the detachment phenotype in flies with reduced ßPS integrins. Taken together, our data suggest that Osiris17 is an endosome related protein that contributes to epithelial remodeling and morphogenesis by assisting basal integrins localization in insects.


Asunto(s)
Proteínas de Drosophila , Integrinas , Animales , Integrinas/metabolismo , Drosophila/genética , Epitelio/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Matriz Extracelular/metabolismo
2.
Eur J Neurosci ; 59(7): 1428-1440, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38151046

RESUMEN

Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high-risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol-O-methyltransferase (COMT) genes, and paranoid and motor-impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor-impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor-impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high-risk psychotic symptoms in MAUD patients.


Asunto(s)
Metanfetamina , Polimorfismo de Nucleótido Simple , Humanos , Catecol O-Metiltransferasa/genética , Dopamina , Metanfetamina/efectos adversos , Genotipo , Metilación
3.
Virol J ; 20(1): 237, 2023 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-37848986

RESUMEN

BACKGROUND: Aspirin is widely used to treat various clinical symptoms. Evidence suggests that aspirin has antiviral properties, but little is known about its specific effect against rotavirus. METHODS: MA104, Caco-2, and CV-1 cells were infected with rotavirus, and aspirin was added after 12 h. Viral mRNA and titer levels were measured by qRT-PCR and immunofluorescence assays. For in vivo validation, forty specific-pathogen-free SD rats were randomly divided into oral aspirin (ASP) groups and control (NC) groups. 16 S rRNA gene sequencing was performed to identify gut microbiota. After 6 months of continuous ASP/NC administration, the rats were infected with rotavirus. Fecal samples were collected over a 30-day time course, and viral levels were quantified. Proinflammatory cytokines/chemokine levels were measured by ELISA. RESULTS: Aspirin inhibited rotavirus infection in cell lines and in rats. The effects of aspirin on viral replication were associated with the alteration of gut microbiota composition by aspirin, including increased abundance of Firmicutes and decreased abundance of Bacteroidetes after aspirin treatment. Mechanistically, aspirin reduced IL-2 and IL-10 levels, and increased IRF-1 and COX-2 levels. Aspirin blocked rotavirus replication in vitro and in vivo, which might be related to effects on IRF-1, COX-2, chemokines, and gut microbial composition. CONCLUSION: These results indicate that long-term oral aspirin administration reduces rotavirus infection. Intestinal virus infection may be suppressed in elderly patients who take aspirin for a long time. The change of their Gut microbiota may lead to functional disorder of the intestinal tract, which may provide some reference for clinical adjuvant probiotics treatment.


Asunto(s)
Microbioma Gastrointestinal , Infecciones por Rotavirus , Rotavirus , Humanos , Ratas , Animales , Anciano , Rotavirus/genética , Infecciones por Rotavirus/tratamiento farmacológico , Células CACO-2 , Ciclooxigenasa 2 , Ratas Sprague-Dawley , Aspirina/farmacología , ARN Ribosómico 16S/genética
4.
Food Res Int ; 169: 112882, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37254330

RESUMEN

The development of food-derived Xanthine Oxidase (XO) inhibitors is critical to the treatment of hyperuricemia and oxidative stress-related disease. Few studies report on milk protein hydrolysates' XO inhibitory activity, with the mechanism of their interaction remaining elusive. Here, different commercial enzymes were used to hydrolyze α-lactalbumin and bovine colostrum casein. The two proteins hydrolyzed by alkaline protease exhibited the most potent XO inhibitory activity (bovine casein: IC50 = 0.13 mg mL-1; α-lactalbumin: IC50 = 0.28 mg mL-1). Eight potential XO inhibitory peptides including VYPFPGPI, GPVRGPFPIIV, VYPFPGPIPN, VYPFPGPIHN, QLKRFSFRSFIWR, LVYPFPGPIHN, AVFPSIVGR, and GFININSLR (IC50 of 4.67-8.02 mM) were purified and identified from alkaline protease hydrolysates by using gel filtration, LC-MS/MS and PeptideRanker. The most important role of inhibiting activity of peptides is linked to hydrophobic interactions and hydrogen bonding based on the results of molecular docking and molecular dynamics simulation. The enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein could be a competitive candidates for hyperuricemia-resisting functional food.


Asunto(s)
Hiperuricemia , Lactalbúmina , Animales , Bovinos , Femenino , Embarazo , Lactalbúmina/química , Xantina Oxidasa , Caseínas/química , Cromatografía Liquida , Calostro , Simulación del Acoplamiento Molecular , Espectrometría de Masas en Tándem , Péptidos/química , Inhibidores Enzimáticos/farmacología
5.
Cell Prolif ; 56(10): e13478, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37060186

RESUMEN

Lactate is not only an endpoint of glycolysis but is gradually being discovered to play the role of a universal metabolic fuel for energy via the 'lactate shuttle' moving between cells and transmitting signals. The glycolytic-dependent metabolism found in tumours and fast-growing cells has made lactate a pivotal player in energy metabolism reprogramming, which enables cells to obtain abundant energy in a short time. Moreover, lactate can provide favourable conditions for tumorigenesis by shaping the acidic tumour microenvironment, recruiting immune cells, etc. and the recently discovered lactate-induced lactylation moves even further on pro-tumorigenesis mechanisms of lactate production, circulation and utilization. As with other epigenetic modifications, lactylation can modify histone proteins to alter the spatial configuration of chromatin, affect DNA accessibility and regulate the expression of corresponding genes. What's more, the degree of lactylation is inseparable from the spatialized lactate concentration, which builds a bridge between epigenetics and metabolic reprogramming. Here, we review the important role of lactate in energy reprogramming, summarize the latest finding of lactylation in tumorigenesis and try to explore therapeutic strategies in oncotherapy that can kill two birds with one stone.


Asunto(s)
Ácido Láctico , Neoplasias , Humanos , Neoplasias/genética , Carcinogénesis , Histonas , Transformación Celular Neoplásica , Epigénesis Genética , Microambiente Tumoral
6.
Acta Pharmacol Sin ; 44(8): 1536-1548, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37012494

RESUMEN

Autophagy-lysosome system plays a variety of roles in human cancers. In addition to being implicated in metabolism, it is also involved in tumor immunity, remodeling the tumor microenvironment, vascular proliferation, and promoting tumor progression and metastasis. Transcriptional factor EB (TFEB) is a major regulator of the autophagy-lysosomal system. With the in-depth studies on TFEB, researchers have found that it promotes various cancer phenotypes by regulating the autophagolysosomal system, and even in an autophagy-independent way. In this review, we summarize the recent findings about TFEB in various types of cancer (melanoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, colorectal cancer, breast cancer, prostate cancer, ovarian cancer and lung cancer), and shed some light on the mechanisms by which it may serve as a potential target for cancer treatment.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal Pancreático , Neoplasias Pulmonares , Neoplasias Pancreáticas , Masculino , Humanos , Autofagia , Microambiente Tumoral
7.
Food Res Int ; 165: 112545, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36869456

RESUMEN

IgG, a biologically active substance in bovine colostrum, is easily inactivated during heat treatment and edible process to lose its biological activity. Nanoemulsion can effectively protect IgG to maintain its biological activity from injurious treatment. In this study, a food-grade nanoemulsion system was developed to protect IgG from heat and acid damage. It can be found that the residual rate of nanoemulsion-protected IgG reaches 87.1 % after 10 min at 72 °C. After 5 min at 82 °C, the residual rate of IgG in nanoemulsion was 18.7 % higher than that in PBS. In the simulated gastric fluid at pH 2.0, the residual rate of IgG in the nanoemulsion reacted for 4 h was 21.5 % higher than that in PBS. It indicated that nanoemulsion system can improve the heat and acid resistance of IgG compared with others, which is attributed to the lowest water activity of nanoemulsion. The contents of hydroperoxide and malondialdehyde in the milk after storage for 72 h with nanoemulsion-protected IgG were 0.12 meq/kg and 0.04 mg/kg, respectively, less than that of PBS-protected IgG. IgG is protected by nanoemulsion can effectively protect its activity during processing, which provides a theoretical basis for its direct application in liquid milk.


Asunto(s)
Calor , Leche , Animales , Bovinos , Peróxido de Hidrógeno , Malondialdehído , Inmunoglobulina G
8.
Brain Behav ; 13(2): e2876, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36621889

RESUMEN

OBJECTIVE: Attractin (ATRN) is a widely expressed member of the cell adhesion and guidance protein family in humans that is closely related to cellular immunity and neurodevelopment. However, while previous studies in our laboratory have confirmed the effect of ATRN mutations on long-term memory, its specific role and the molecular mechanism by which it influences spatial cognition are poorly understood. METHODS: This study aimed to examine the effect of ATRN mutations on working memory in water maze with a novel ATRN-mutant rat generated by the CRISPR/Cas9 system; the mutation involved the substitution of the 505th amino acid, glycine (G), with cysteine (C), namely, a mutation from GGC to TGC. The changes in myelin basic protein (MBP) expression in rats were also analyzed with the western blot. RESULTS: The ATRN-G505C(KI/KI) rats exhibited significant increases in the required latency and distance traveled to locate the escape platform in a Morris water maze test of working memory. In addition, the expression of MBP was reduced in ATRN-mutant rats, as shown in the western blot analysis. CONCLUSION: Our results indicate that ATRN gene mutations may directly lead to the impairment of working memory in the water maze; this impairment may be due to the inhibition of MBP expression, which in turn affects the spatial cognition.


Asunto(s)
Memoria a Corto Plazo , Animales , Humanos , Ratas , Aprendizaje por Laberinto , Mutación
9.
Food Chem ; 405(Pt A): 134796, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36335724

RESUMEN

An allergen epitope is a part of molecules that can specifically bind to immunoglobulin E (IgE), causing an allergic reactions. To predict protein epitopes and their binding ability to IgE, quantitative structure-activity relationship (QSAR) models were established using four algorithms combined with the selected chemical descriptors. The model predicted the binding capabilities of the epitopes to IgE with the R2 and root mean squared error (RMSE) as 0.7494 and 0.2375, respectively. The model's performance was validated using an enzyme-linked immunosorbent assay (ELISA). The results showed that the established QSAR model could efficiently and accurately predict the allergic reaction of food protein epitopes. The prediction results of the model and the experimental results were consistent, with a Pearson correlation coefficient of 0.8956. The results from both the QSAR model and in vitro experiments indicated that amino acid sequence 116-130 was a novel IgE-binding epitope of ß-LG.


Asunto(s)
Hipersensibilidad a los Alimentos , Humanos , Epítopos/química , Inmunoglobulina E/metabolismo , Alérgenos/química , Aprendizaje Automático
10.
Food Funct ; 13(24): 12674-12685, 2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36382616

RESUMEN

With the acceleration of the pace of life, people may face all kinds of pressure, and anxiety has become a common mental issue that is seriously affecting human life. Safe and effective food-derived compounds may be used as anti-anxiety compounds. In this study, anti-anxiety compounds were collected and curated for database construction. Quantitative structure-activity relationship (QSAR) models were developed using a combination of various machine-learning approaches and chemical descriptors to predict natural compounds in food with anti-anxiety effects. High-throughput molecular docking was used to screen out compounds that could function as anti-anxiety molecules by inhibiting γ-aminobutyrate transaminase (GABA-T) enzyme, and 7 compounds were screened for in vitro activity verification. Pharmacokinetic analysis revealed three compounds (quercetin, lithocholic acid, and ferulic acid) that met Lipinski's Rule of Five and inhibited the GABA-T enzyme to alleviate anxiety in vitro. The established QSAR model combined with molecular docking and molecular dynamics was proved by the synthesis and discovery of novel food-derived anti-anxiety compounds.


Asunto(s)
Simulación de Dinámica Molecular , Relación Estructura-Actividad Cuantitativa , Humanos , Simulación del Acoplamiento Molecular , Ácido gamma-Aminobutírico
11.
Front Surg ; 9: 970178, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36277293

RESUMEN

Background: Pancreatic neuroendocrine tumors (pNETs) and solid pseudopapillary tumors (SPTs) are two of the most common pancreatic neoplasms with different treatment procedures. However, the broad heterogeneity of pNETs and SPTs in clinical manifestations and radiological features often confuse the presurgical discrimination in clinical practice, and the clinical and molecular differentiation of the two tumors remains elusive to date. We presume that a large and comprehensive study into the multimodality features of pNETs and SPTs is necessary for precise clinical management. Methods: We collected and analyzed the clinicopathological information and multimodality features of nonfunctional pNET and SPT patients, for a total of 631 cases from 2006 to 2021. Univariate analysis of imaging features, including contrast-enhanced computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound (EUS) and nuclear medicine imaging, and clinical characteristics was performed, and CT features and clinical information were integrated to establish a nomogram model. Results: We recruited 354 nonfunctional pNET and 277 SPT patients in our cohort. Regarding demographic information, pNET patients had a lower female percentage (55.4% vs. 72.9%), smaller tumor size (2.8 vs. 4.8 cm), and older age (53.4 vs. 35.3 years). In CT imaging and EUS, pNETs tended to appear as solid and homogenous lesions with strong enhancement intensity. Multifocal lesions, duct dilation, and lymph node (LN) enlargement were more likely to be observed in pNETs, while calcification was more common in SPT lesions. On positron emission tomography (PET)/CT, pNETs exhibited significant sensitivity to somatostatin receptor scintigraphy (SRS), with positive rates of 81.4% and 95% on 99mTc-HYNIC-TOC and 68Ga-DOTATATE PET/CT, respectively, while SPTs were all negative on SRS. Multivariate analysis identifies tumor size, age, enhancement intensity, calcification, and LN enlargement as statistically significant variables. Conclusions: Compared to SPT patients, pNET patients exhibit an older age and smaller tumor size. CT manifestations of strong intensity, LN enlargement, and no calcification could indicate a higher possibility of pNET. Meanwhile, the similarity in the immunohistochemical profile indicates that the two tumors could potentially develop from the same origin.

12.
Rev Sci Instrum ; 93(8): 084703, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36050067

RESUMEN

A beam scanning antenna based on an all-metal lens is presented for high-power microwave (HPM) application in this paper. This design includes a feed antenna and two layers of different all-metal lenses, whose prototypes operating at 14.25 GHz have been successfully designed and fabricated with an aperture radius of 300 mm. A full transmission phase range of 360° can be achieved with a transmission efficiency of over 99% by rotating the cross-slot on the lens elements. The results of the low-power tests depict that the designed antenna can realize a beam scanning range of 120° revolving cone angle with the side lobe below -10 dB and the reflection coefficient less than -16 dB. The high-power tests demonstrate that the power handling capacity of the antenna is higher than 350 MW in sulfur hexafluoride (SF6). In addition, both the designed lenses have a bandwidth of more than 100 MHz. All the merits show that our designed all-metal lens antenna has a great potential to be applied in HPM systems.

13.
Food Chem ; 373(Pt A): 130999, 2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-34710694

RESUMEN

Human health can be damaged by free radicals, and antioxidant peptides are excellent radical scavengers. Antioxidant tripeptides data set based on 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulofnic acid) (ABTS) assay was created, 9 types of descriptors were integrated and 4 quantitative structure-activity relationship (QSAR) models were constructed in this study. Several structural factors influencing the activity of antioxidant tripeptides and the dominant amino acids at each position of tripeptides were revealed by the optimal model. Ten food-derived tripeptides with higher activity were selected for synthesis and activity determination. Molecular docking results demonstrated that these tripeptides were stably bound to the Keap1 receptor, further elucidating the antioxidant mechanism. It was known from the simulation of gastrointestinal digestion experiments that the model results possessed a guiding effect on the selection of proteins with high antioxidant activity. The performance of the model was proved to be robust after validation.


Asunto(s)
Antioxidantes , Factor 2 Relacionado con NF-E2 , Humanos , Proteína 1 Asociada A ECH Tipo Kelch , Simulación del Acoplamiento Molecular , Péptidos
14.
Drug Alcohol Depend ; 229(Pt B): 109047, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34710713

RESUMEN

BACKGROUND: The Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) was developed to assess substance-use disorders and other psychiatric traits. We translated the SSADDA into Chinese and evaluated its inter-rater reliability and concurrent validity in diagnosing DSM-IV methamphetamine (MA) dependence and DSM-5 MA-use disorder (MUD). METHODS: The sample comprised 231 participants who were interviewed using the Chinese SSADDA and the Mini-International Neuropsychiatric Interview (Chinese MINI) for concurrent validation. Of the 231 participants, 191 were interviewed by two different interviewers two weeks apart. We evaluated the inter-rater reliability and concurrent validity of the diagnoses using percent agreement and Cohen's kappa coefficient (κ). Cohen's linear weighted kappa was used to assess the reliability of DSM-5 MUD severity. RESULTS: It showed good inter-rater reliability and no significant differences among the DSM-5 MUD (κ = 0.71), DSM-IV MA abuse or dependence (κ = 0.72), and the DSM-IV diagnoses of MA dependence (κ = 0.66) and abuse (κ = 0.68) tested separately. The weighted kappa was 0.67 across the three DSM-5 MUD severity levels. The reliability of each individual diagnostic criterion for DSM-5 MUD ranged from fair to excellent (κ = 0.41-0.80), except for "repeated attempts to quit/control use" (κ = 0.38). The concurrent validity based on MINI-derived diagnoses ranged from good to excellent (κ = 0.65-0.78). CONCLUSIONS: This study shows that the Chinese version of SSADDA has good reliability and validity among Chinese MA users.


Asunto(s)
Alcoholismo , Trastornos Relacionados con Anfetaminas , Metanfetamina , Alcoholismo/diagnóstico , Alcoholismo/epidemiología , Trastornos Relacionados con Anfetaminas/diagnóstico , China/epidemiología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Humanos , Reproducibilidad de los Resultados
15.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 579-583, 2021 Aug.
Artículo en Chino | MEDLINE | ID: mdl-34494529

RESUMEN

Objective To evaluate lateral pterygoid muscle(LPM)contraction in the patients with temporomandibular disorders(TMD)based on 3D-T2 weighted imaging(3D-T2WI).Multiplanar reconstruction(MPR)was employed to measure the length of LPM in the images taken in closed-and open-mouth positions. Methods Seventeen TMD patients [age of(29.82±10.70)years,males/females=8/9] and 13 normal volunteers [control,age of(23.54±3.31)years,males/females=6/7] received 3D-T2WI of the temporomandibular joints in closed-and open-mouth positions from November 2019 to April 2020 in Department of Radiology,Hainan Hospital of Chinese PLA General Hospital.According to the position of the discs,the subjects were classified into the following groups:TMD with disc displacement without reduction(TMD-DDwoR),TMD with disc displacement with reduction(TMD-DDwR),TMD without disc displacement(TMDwoDD),and normal control without disc displacement(NCwoDD).MPR was employed to measure the maximal length of the superior belly of LPM.One-way analysis of variance,receiver operating characteristic curve,and permutation test were employed for the statistical analyses. Results The contraction of LPM was significantly shorter in TMD-DDwoR group [(3.36±1.96)mm] than in TMDwoDD group [(7.90±3.95)mm],NCwoDD group [(8.77±3.13)mm](F=12.891,P=0.000),and TMD-DDwR group[(7.12±3.69)mm](χ2=5.314,P=0.031). Conclusion This study confirmed that the contraction of LPM decreased in patients with TMD-DDwoR,which provided imaging evidence for the study of disc displacement mechanism in TMD patients.


Asunto(s)
Luxaciones Articulares , Trastornos de la Articulación Temporomandibular , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Contracción Muscular , Músculos Pterigoideos/diagnóstico por imagen , Disco de la Articulación Temporomandibular , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Adulto Joven
16.
Neuroscience ; 466: 101-108, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34000322

RESUMEN

Attractin (ATRN), an autosomal recessive gene that is widely distributed in the brain, is involved in the execution of a variety of brain functions and associated with certain neuropsychiatric disorders. Here, we introduce a novel rat strain harboring a mutation in ATRN that was generated by knocking in ATRN-G505C via the CRISPR/Cas9 system. We assessed the behavioral performance of these mutant ATRN knock-in rats. The G505C mutation was introduced into exon 9, and a synthetic primer was inserted into introns 8-9 for genotyping. The 505th amino acid, a Gly (G) residue, was mutated to a Cys (C) residue, i.e., GGC was mutated to TGC. Behavioral experiments showed that homozygous ATRN rats spent significantly more time searching for the escape platform in the acquisition trial and significantly less time in the target area in the probe trial in the Morris water maze (MWM) test and traveled a significantly shorter distance in the open field test (OFT) than wild-type rats. In addition, Western blot analysis and immunohistochemistry showed that rats with the mutant ATRN gene exhibited significantly reduced expression of brain-derived neurotrophic factor (BDNF). In summary, our results indicate that mutations in the ATRN gene directly lead to learning and memory impairments and slight motor deficits. These findings provide new clues for the mechanism by which mutant ATRN induces neurodegenerative changes.


Asunto(s)
Encéfalo , Aprendizaje Espacial , Animales , Exones , Homocigoto , Aprendizaje por Laberinto , Mutación , Ratas
17.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(1): 57-62, 2021 Feb 28.
Artículo en Chino | MEDLINE | ID: mdl-33663664

RESUMEN

Objective To investigate the intra-and inter-observer reproducibility of iodine concentrations of abdominal parenchymal organs based on spectral CT.Methods The water-free iodine images of the venous phase were retrospectively obtained from 50 patients with abdominal dynamic spectral CT scans.The iodine concentrations were measured in the left,right and caudate lobes of liver,spleen,pancreas and bilateral kidneys.Intraclass correlation coefficient(ICC)and Bland-Altman plot were employed to analyze the intra-and inter-observer reproducibility.Results The intra-observer ICCs of the left,right and caudate lobes of liver,spleen,pancreas,and left and right kidneys were 0.938(0.894,0.965),0.932(0.884,0.961),0.939(0.895,0.965),0.947(0.909,0.970),0.912(0.851,0.949),0.946(0.906,0.969)and 0.907(0.842,0.946),which indicated good intra-observer reproducibility.The inter-observer ICCs of the left,right and caudate lobes of liver,spleen,pancreas,and left and right kidneys were 0.947(0.909,0.970),0.927(0.875,0.958),0.943(0.902,0.968),0.956(0.924,0.975),0.934(0.887,0.962),0.927(0.875,0.958)and 0.892(0.818,0.937),which indicated good inter-observer reproducibility.Bland-Altman plots presented that more than 95% points of the intra-observer differences located within 95% CI of limits of agreement for the caudate lobe of liver,spleen,pancreas and bilateral kidneys,which was same as inter-observer differences of the caudate lobe of liver,spleen and right kidney.Conclusion The iodine concentration measurement based on the spectral CT presented good intra-and inter-observer reproducibility for the caudate lobe of liver and spleen.


Asunto(s)
Yodo , Humanos , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
18.
Biomed Pharmacother ; 133: 111064, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33378966

RESUMEN

COVID-19 is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early reported symptoms include fever, cough, and respiratory symptoms. There were few reports of digestive symptoms. However, with COVID-19 spreading worldwide, symptoms such as vomiting, diarrhoea, and abdominal pain have gained increasing attention. Research has found that angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, is strongly expressed in the gastrointestinal tract and liver. Whether theoretically or clinically, many studies have suggested a close connection between COVID-19 and the digestive system. In this review, we summarize the digestive symptoms reported in existing research, discuss the impact of SARS-CoV-2 on the gastrointestinal tract and liver, and determine the possible mechanisms and aetiology, such as cytokine storm. In-depth exploration of the relationship between COVID-19 and the digestive system is urgently needed.


Asunto(s)
COVID-19/complicaciones , Enfermedades Gastrointestinales/etiología , Hepatopatías/etiología , Pandemias , SARS-CoV-2/patogenicidad , Enzima Convertidora de Angiotensina 2/metabolismo , Anorexia/etiología , Antivirales/efectos adversos , Conductos Biliares/metabolismo , Conductos Biliares/virología , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Comorbilidad , Síndrome de Liberación de Citoquinas/etiología , Efecto Citopatogénico Viral , Enfermedades Gastrointestinales/epidemiología , Microbioma Gastrointestinal , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/patología , Tracto Gastrointestinal/virología , Humanos , Inmunosupresores/efectos adversos , Hígado/metabolismo , Hígado/patología , Hígado/virología , Hepatopatías/epidemiología , Trasplante de Hígado , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/virología , Complicaciones Posoperatorias , Receptores Virales/metabolismo
19.
Neurosci Lett ; 731: 135024, 2020 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-32380142

RESUMEN

Prepulse inhibition (PPI), a measure of sensorimotor gating, has been shown to be disrupted in several animal models of neuropsychiatric disorders, such as schizophrenia. The neural circuits involving the hippocampus and nucleus accumbens (NAC) have been studied in rats to uncover the neurochemical and neuroanatomical substrates that regulate PPI. Majority of the studies of the hippocampus on PPI to date have been focused on CA1, CA2, and dentate gyrus (DG) area. Little is known about the role of the subiculum, which maintains the hippocampal formation intact, on the sensorimotor gating. In this study, the PPI disruption was induced by intraperitoneal injection of MK-801 in rats, and the neuronal activity in the dorsal and ventral subiculum by c-Fos immunostaining was examined. The projections from the subiculum to the nucleus accumbens (NAC) were detected by retrograde tracing of cholera toxin B subunit, in the PPI dysfunctional animals. The results showed an increase in neuronal activity in the ventral subiculum (vSub) while remaining constant in the dorsal subiculum during PPI disruption. The excitatory projections from the vSub to the NAC shell were significantly enhanced when PPI was disrupted. Muscimol Inhibition of vSub could significantly ameliorate the MK801-induced PPI deficit. This data suggests that the enhancement of neuronal activity in the vSub was associated with the PPI impairment, possibly due to the enhanced excitatory output from vSub the NAC shell.


Asunto(s)
Vías Nerviosas/fisiología , Neuronas/fisiología , Núcleo Accumbens/fisiología , Inhibición Prepulso/fisiología , Animales , Maleato de Dizocilpina/farmacología , Masculino , Vías Nerviosas/efectos de los fármacos , Neuronas/efectos de los fármacos , Inhibición Prepulso/efectos de los fármacos , Ratas Sprague-Dawley , Reflejo de Sobresalto/efectos de los fármacos , Reflejo de Sobresalto/fisiología
20.
Neural Regen Res ; 15(9): 1701-1708, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32209774

RESUMEN

The pathophysiology of migraine is complex. Neuroimaging studies reveal functional and structural changes in the brains of migraine patients. We sought to explore regional volume differences in intracranial structures in patients with episodic and chronic migraine. Sixteen episodic migraine patients, 16 chronic migraine patients, and 24 normal controls were recruited and underwent 3.0 T MRI scanning. The volumes of 142 brain regions were calculated by an automatic volumetric algorithm and compared with clinical variables. Results demonstrated that the volumes of specific regions in the frontal and occipital lobes, and the right putamen, were increased and the volume of the fourth ventricle was decreased in the episodic migraine patients compared with controls. The volumes of the left basal forebrain, optic chiasm, and, the fourth ventricle were decreased in the chronic migraine patients, while the occipital cortex and the right putamen were larger. Compared to episodic migraine patiants, chronic migraine patients displayed larger left thalamus and smaller frontal regions. Correlation analysis showed that headache frequency was negatively correlated with the volume of the right frontal pole, right lateral orbital gyrus, and medial frontal lobes and positively correlated with the volume of the left thalamus. The sleep disturbance score was negatively correlated with the volume of the left basal forebrain. This suggests that migraine patients have structural changes in regions associated with pain processing and modulation, affective and cognitive processing, and visual perception. The remodeling of selective intracranial structures may be involved in migraine attacks. This study was approved by the Ethics Committee of Chinese PLA General Hospital (approval No. S2018-027-02) on May 31, 2018.

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