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1.
Mov Disord ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34820915

RESUMO

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.

2.
Amino Acids ; 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837554

RESUMO

Taurine (Tau) is one of the most abundant amino acids in the brain and regulates physiological functions in the central nervous system, including anti-inflammatory effects. There is growing evidence that microglia-mediated neuro-inflammatory responses are an integral part of Parkinson's disease (PD) onset and progression. Among the many factors regulating the inflammatory response, phosphatidylinositol-3 kinase (PI3K) is susceptible to activation by a variety of cytokines and physicochemical factors, and subsequently recruits signaling proteins containing the pleckstrin homology structural domain to further regulate protein kinase B (AKT) expression involved in the regulation of the intracellular immune response and inflammatory response. Therefore, we established a PD mouse model using paraquat (PQ) intraperitoneal injection staining to explore the mechanism of Tau action on PI3K/AKT signaling pathway. Our study showed that PD mice with Tau intervention recovered motor and non-motor functions to some extent, and the number of dopaminergic (DAc) neurons in the substantia nigra and the level of dopamine (DA) secretion in the striatum were also significantly increased compared with the PQ-dyed group, and the protein content of PI3K and PDK-1 and the phosphorylation level of AKT were reduced in parallel with the reduction in the expression of microglia and related inflammatory factors. In conclusion, our results suggest that Tau may regulate microglia-mediated inflammatory responses through inhibition of the PI3K/AKT pathway in the midbrain of PD mice, thereby reducing DAc neurons damage.

3.
Environ Pollut ; 293: 118505, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34785291

RESUMO

Perfluorooctanoic acid (PFOA) as an emerging environmental contaminant, has become ubiquitous in the environment. It is of significance to study bioconcentration and tissue distribution of aquatic organisms for predicting the persistence of PFOA and its adverse effects on the environment and human body. However, the distribution of PFOA in different tissues is a complex physiological process affected by many factors. It is difficult to be accurately described by a simple kinetic model. In present study, a new strategy was introduced to research the PFOA distribution in tissues and estimate the exposure stages. Zebrafish were continuously exposed to 25 mg/L PFOA for 30 days to simulate environmental process. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) method was used to monitor the spatio-temporal distribution of PFOA in zebrafish tissues. By analyzing the law of change obtained from the high spatial resolution MSI data, two different enrichment trends in ten tissues were summarized by performing curve fitting. Analyzing the ratio of two types of curves, a new "exposure curve" was defined to evaluate the exposure stages. With this model, three levels (mild, moderate, and deep pollution stage) of PFOA pollution in zebrafish can be simply evaluated.

4.
Exp Cell Res ; 408(1): 112813, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34492266

RESUMO

Keloids are benign skin tumors characterized by aggressive growth. To date, there is no exact treatment because little is known about its pathological mechanism. Therefore, it is important to investigate the mechanism of its occurrence and development to identify therapeutic targets. In this study, the expression of Kindlin-2 was higher in keloid fibroblasts (KFs) than in normal skin fibroblasts (NFs). In vitro experiments showed that knocking down Kindlin-2 in KFs could promote cell apoptosis and inhibit cell proliferation, cell migration and invasion, and contractile capability. Western blot results showed that the phosphorylation of Smad3 in KFs was inhibited after knocking down Kindlin-2, inhibiting the activation of the Smad pathway. Moreover, knocking down Kindlin-2 increased the expression of Fas and FasL in KFs, which demonstrated that knocking down Kindlin-2 promoted the activation of the exogenous apoptotic pathway of KFs and then facilitated apoptosis. The above results revealed that knocking down Kindlin-2 in KFs can inhibit the activation of the Smad pathway and promote the activation of the Fas/FasL exogenous apoptosis pathway, thereby altering the cytological function of KFs. Therefore, Kindlin-2 might play an important role in the occurrence and development of keloids and could become a new target to treat keloids.


Assuntos
Movimento Celular/fisiologia , Fibroblastos/metabolismo , Queloide/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Proliferação de Células/fisiologia , Células Cultivadas , Matriz Extracelular/metabolismo , Proteína Ligante Fas/metabolismo , Feminino , Fibroblastos/patologia , Humanos , Queloide/patologia , Masculino , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta1/metabolismo
5.
Langmuir ; 37(35): 10461-10468, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34431681

RESUMO

A colloidal nanocrystal cluster (CNC) is a hierarchical nanostructure formed by clustering several nanocrystals into one nano-ensemble, which may exhibit unique optical or catalytic properties different from individual nanocrystals owing to the mutual interactions among neighboring component nanocrystals. However, there is still no universal synthetic route that could be applicable to diverse material compositions with precisely controlled hierarchical structures (i.e., nanocrystal number density, component nanocrystal size, and overall diameter of the CNC) up to now. Herein, a general and novel synthetic strategy was reported for crafting a wide range of inorganic CNCs (i.e., noble metal, semiconductor, and metal oxide) via utilizing amphiphilic star-like poly(4-vinylpyridine)-block-polystyrene diblock copolymers as nanoreactors prepared by sequential atom transfer radical polymerization. The hierarchical structure of rationally designed CNCs could be readily tailored by varying the P4VP molecular weight of star-like nanoreactors and the parameter optimization during the CNC preparation process, which was inaccessible by conventional synthetic methods.

6.
Neurol Sci ; 42(10): 4095-4107, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34379238

RESUMO

Startle, a basic alerting reaction common to all mammals, is described as a sudden involuntary movement of the body evoked by all kinds of sudden and unexpected stimulus. Startle syndromes are heterogeneous groups of disorders with abnormal and exaggerated responses to startling events, including hyperekplexia, stimulus-induced disorders, and neuropsychiatric startle syndromes. Hyperekplexia can be attributed to a genetic, idiopathic, or symptomatic cause. Excluding secondary factors, hereditary hyperekplexia, a rare neurogenetic disorder with highly genetic heterogeneity, is characterized by neonatal hypertonia, exaggerated startle response provoked by the sudden external stimuli, and followed by a short period of general stiffness. It mainly arises from defects of inhibitory glycinergic neurotransmission. GLRA1 is the major pathogenic gene of hereditary hyperekplexia, along with many other genes involved in the function of glycinergic inhibitory synapses. While about 40% of patients remain negative genetic findings. Clonazepam, which can specifically upgrade the GABARA1 chloride channels, is the main and most effective administration for hereditary hyperekplexia patients. In this review, with the aim at enhancing the recognition and prompting potential treatment for hyperekplexia, we focused on discussing the advances in hereditary hyperekplexia genetics and the expound progress in pathogenic mechanisms of the glycinergic-synapse-related pathway and then followed by a brief overview of other common startle syndromes.


Assuntos
Hiperecplexia , Rigidez Muscular Espasmódica , Animais , Humanos , Hiperecplexia/genética , Recém-Nascido , Rigidez Muscular , Receptores de Glicina/genética , Reflexo de Sobressalto/genética , Rigidez Muscular Espasmódica/genética
7.
Angew Chem Int Ed Engl ; 60(40): 21918-21926, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34309164

RESUMO

The first example of luminescent monosubstituted polyacetylenes (mono-PAs) is presented, based on a contracted cis-cisoid polyene backbone. It has an excellent circularly polarized luminescence (CPL) performance with a high dissymmetric factor (up to the order of 10-1 ). The luminescence stems from the helical cis-cisoid PA backbone, which is tightly fixed by the strong intramolecular hydrogen bonds, thereby reversing the energy order of excited states and enabling an emissive energy dissipation. CPL switches are facilely achieved by the solvent and temperature through reversible conformational transition. By taking advantages of fast response and high sensitivity, the thin film of mono-PAs could be used as a CPL-based probe for quantitative detection of trifluoroacetic acid with a wider linear dynamic range than those of photoluminescence and circular dichroism. This work opens a new avenue to develop novel smart CPL materials through modulating conformational transition.

8.
Exp Cell Res ; 405(2): 112680, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34090862

RESUMO

Ferredoxin reductase (FDXR), a mitochondrial membrane-associated flavoprotein, is essential for electron transfer and modulates p53-dependent apoptosis in cancer cells.FDXR may be implicated in epidermal and sebocytic differentiation, but its explicit function in sebocytes remains to be elucidated. In the present study, immunohistochemistry revealed that FDXR expression was increased in sebaceous cells of acne lesions. FDXR, PPARγ, LXRα/ß, SREBP1 and Sox9 expression was incremental during sebocyte differentiation. FDXR overexpression induced by Ad-GFP-FDXR infection enhanced differentiation, reactive oxygen species (ROS), lipogenesis and PPARγ expression, and consequnently inhibited proliferation in SZ95 sebocytes. Flow cytometry showed that FDXR overexpression induced significant blockade of G2/M phase but had no effect on sub-G1 (apoptotic) sebocytes. Insulin-like growth factor-1 (IGF-1)-induced FDXR and PPARγ expression and lipogenesis were abolished by pretreatment with PI3K inhibitor LY294002. These results suggest that FDXR overexpression might promote differentiation and lipogenesis via ROS production and suppress proliferation via G2/S blockade in SZ95 sebocytes. IGF-1 could facilitate differentiation and lipogenesis through PI3K/Akt/FDXR pathway. FDXR could serve as a potential marker of advanced sebaceous differentiation, and its overexpression may be involved in the development of acne lesions.


Assuntos
Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Ferredoxinas/farmacologia , Lipogênese/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Humanos
9.
J Colloid Interface Sci ; 600: 421-429, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34023703

RESUMO

Multi-stimuli responsive fluorescence probe could pave the way for monitoring more complex environmental changes. Here we prepared multifunctional nanoparticle Fe3O4@SiO2@P(DMAEMA-co-TPEE), which displayed yolk-shell morphology with well-defined polymer brush. With superparamagnetic Fe3O4 component and pH/temperature dual sensitive PDMAEMA polymer brush, the as prepared nanoparticles (YS-NPs) exhibited as multi-stimuli responsive fluorescence probe for real-time visual monitoring of environmental changes such as magnetic field, temperature and pH. Such YS-NPs could also be applied as a sensitive detector for CO2 in aqueous solution. Notably, the solution of YS-NPs showed high colloidal stability during the environmental changes, and surface aggregation-induced emission (S-AIE) was proposed for the aggregation of TPE residue on the surface of YS-NPs.


Assuntos
Nanocompostos , Nanopartículas , Polímeros , Temperatura
10.
J Phys Chem Lett ; 12(13): 3456-3463, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33792312

RESUMO

The past few years witnessed the rapid development of bottom-up synthesis strategies for preparing various nanostructures (i.e., nanoparticles, nanorods, nanowires, etc.) with distinct morphology-dependent properties. In this study, we reported a facile and efficient synthesis method for preparing anatase titanium dioxide (TiO2) nanorings based on multiarm, starlike amphiphilic polystyrene-b-poly(acrylic acid) (PS-b-PAA) diblock copolymers as nanoreactors which were prepared via a sequential atom-transfer radical polymerization (ATRP) technique followed by the conversion of polystyrene-b-poly(tert-butyl acrylate) (PS-b-PtBA) to PS-b-PAA. The outer PAA block of nanoreactors possessed carboxylic acid groups which could coordinate with a titanium precursor followed by high-temperature calcination to form crystalline TiO2 nanorings. The living nature of ATRP enabled the precise preparation of starlike diblock copolymer nanoreactors with a controlled length of each block (i.e., PtBA and PS), thereby tailoring the inner diameter and wall thickness of the resulting TiO2 nanorings, which were inaccessible to conventional routes.

11.
Biomed Chromatogr ; 35(9): e5140, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33830528

RESUMO

Owing to the complexity of the composition of herbal and dietary supplements, it is a challenging problem to efficiently screen and identify active or toxic compounds. Psoralea corylifolia L. (PCL) was selected as the subbject to establish a methodology for rapid screening and identification of hepatotoxic compounds. High-content imaging, ultra-performance liquid chromatography and high-resolution mass spectrometry were used in this study to detect the hepatotoxicity and identify unknown compounds in PCL samples. Then, putative toxic compounds which are highly related to hepatotoxicity were screened by spectrum-toxicity correlation analysis, and the toxicity intensity verified by high-content imaging. The maximum nontoxic dose of processed samples with good detoxification effect reduced more than 9 times compared with unprocessed raw medicinal materials. Spectrum-toxicity correlation analysis showed that bavachinin A, bavachin, isobavachalcone and neobavaisoflavone had high correlation with the hepatotoxicity of PCL, and psoralen and isopsoralen had low correlation with hepatotoxicity. This study verified the hepatotoxicity of these six putative compound monomers, proving the results of spectrum-toxicity correlation analysis. Based on the correlation analysis of high-resolution mass spectrometry of detection compounds and high-content imaging of hepatocyte toxicity data, the potential toxic compound of herbal and dietary supplement products can be quickly and accurately screened.


Assuntos
Suplementos Nutricionais/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Hepatócitos/efeitos dos fármacos , Psoralea/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ficusina/toxicidade , Flavonoides/toxicidade , Humanos , Isoflavonas/toxicidade , Espectrometria de Massas/métodos , Imagem Molecular/métodos
12.
Diabetes Metab Syndr Obes ; 14: 1253-1266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33776462

RESUMO

Purpose: The activation of autophagy has potential protective effect on diabetic nephropathy (DN) podocyte injury, and the AMPK/mTOR signaling pathway is an important regulatory pathway of autophagy. Emodin has been reported to effectively delay DN progression; however, the therapeutic mechanisms involved in vivo remain ambiguous. The present study aimed to elucidate the mechanism of emodin in improving renal tissue and podocyte injury in DN by regulating the AMPK/mTOR-autophagy signaling pathway. Methods: All rats were divided into 4 groups: a Sham group, a Vehicle group, a low-dose emodin (LD-Emo) group (20 mg/kg/day) and a high-dose emodin (HD-Emo) group (40 mg/kg/day). The different doses of Emo and distilled water were daily administrated for 8 weeks after the induction of DN by the unilateral nephrectomy combined with intraperitoneal injections of streptozotocin (STZ). The rats' general status, blood glucose, biochemical parameters, urinary protein excretion, renal histological changes and cell apoptosis in renal tissue, as well as the key protein expressions in the AMPK/mTOR signaling pathway and apoptosis-related proteins were examined, respectively. Results: Emodin ameliorated the general condition, kidney weight and urinary protein excretion of the rats, but has little influence on serum biochemical parameters and did not lower blood glucose; emodin attenuated renal fibrosis including the cell numbers, extracellular matrix rate and collagen area in glomerulus, simultaneously relieved podocyte foot process fusion, up-regulated the expression of nephrin protein and suppressed glomerular and tubular epithelial cell apoptosis. In addition, emodin can induce and enhance autophagy in podocytes including increased expression of LC3-II/I, Beclin-1, p-AMPK protein and decreased expression of p62, p-mTOR protein, as well as increased autophagosomes in podocytes. Conclusion: We have demonstrated that emodin, as a natural regulator in vivo, reduced proteinuria and alleviated renal fibrosis without affecting hyperglycemia in DN rats. The potential mechanisms by which emodin exerts its renoprotective effects in vivo are through suppressing cell apoptosis and enhancing autophagy of podocytes via the AMPK/mTOR signaling pathway in the kidney.

13.
Front Med (Lausanne) ; 8: 644376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777984

RESUMO

Objectives: Autoimmune hepatitis (AIH) can progress into severe outcomes, i.e., decompensated cirrhosis, from remarkable and persistent inflammation in the liver. Considering the energy-expending nature of inflammation, we tried to define the metabolomics signatures of AIH to uncover the underlying mechanisms of cirrhosis development and its metabolic biomarkers. Methods: Untargeted metabolomics analysis was performed on sera samples from 79 AIH patients at the stages (phenotypes) of non-cirrhosis (n = 27), compensated cirrhosis (n = 22), and decompensated cirrhosis (n = 30). Pattern recognition was used to find unique metabolite fingerprints of cirrhosis with or without decompensation. Results: Out of the 294 annotated metabolites identified, 2 metabolic fingerprints were found associated with the development of cirrhosis (independent of the decompensated state, 42 metabolites) and the evolution of decompensated cirrhosis (out of 47 metabolites), respectively. The cirrhosis-associated fingerprints (eigenmetabolite) showed better capability to differentiate cirrhosis from non-cirrhosis patients than the aminotransferase-to-platelet ratio index. From the metabolic fingerprints, we found two pairs of metabolites (Mesobilirubinogen/6-Hydroxynicotinic acid and LysoPA(8:0/0:0)/7alpha-Hydroxycholesterol) calculated as ratio of intensities, which revealed robust abilities to identify cirrhosis or predict decompensated patients, respectively. These phenotype-related fingerprint metabolites featured fundamental energy supply disturbance along with the development of AIH cirrhosis and progression to decompensation, which was characterized as increased lipolysis, enhanced proteolysis, and increased glycolysis. Conclusions: Remodeling of metabolism to meet the liver inflammation-related energy supply is one of the key signatures of AIH in the development of cirrhosis and decompensation. Therefore, drug regulation metabolism has great potential in the treatment of AIH.

14.
Sci Total Environ ; 771: 144888, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33548699

RESUMO

Wildfires, or bushfires, are one of the most destructive natural disasters in Australia, which can cause many deaths of stock, native animals, sometimes humans, and huge impacts on infrastructure. Reconstructing past wildfires and exploring the links between wildfires and climate are essential for understanding the dynamics of wildfires and for predicting future risks. In this study, the frequency of wildfires in northeastern Australia over the past 25,000 years was reconstructed from the charcoal records preserved in peat and lake sediments. The results showed that the frequency of wildfires were relatively low during the cool last glacial period and the warm mid Holocene, indicating that the stable mean climate conditions, whether cool or warm, would not independently initiate increased wildfires in northeastern Australia. The most frequent wildfires occurred during the last deglaciation period, when Earth's climate warmed and the warming rate was the highest over the last 25,000 years, before recent anthropogenic warming. It suggested that the rapid global warming may greatly increase the likelihood of dangerous wildfires in northeastern Australia during the last deglaciation. The wildfires reactivated over the most recent 4000 years, coinciding with amplified climate variability and probably an expansion of human activity. The rapid warming of global climate during the last deglaciation period is an ideal analogue for current anthropogenic global warming. The comparison between fire count and temperature changes in Australia since 2003 also showed that the fire frequency in Australia in recent years is more closely correlated with the warming amplitude, rather than mean temperature. Our results implied that the wildfire risk in northeastern Australia may increase further under the expected accelerating global warming, if human management systems does not intrude. Wildfire modeling could benefit greatly by considering the relationship of fires with climate variability rather than only with stable climate scenarios.

15.
Aging (Albany NY) ; 13(1): 1410-1421, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33406501

RESUMO

In this study, we evaluated the association of modified Glasgow Prognostic Score (mGPS) with prognosis in pancreatic cancer (PC) by performing a meta-analysis. Potentially eligible studies were shortlisted by searching PubMed, Embase, Web of Science, Scopus, and the Cochrane Library. A total of 4,629 patients with PC from 25 studies were finally included in this meta-analysis. Meta-analyses were performed using a random-effects model or fixed-effect model according to heterogeneity. We pooled the hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the association between mGPS and overall survival (OS). The results showed that elevated mGPS correlated with poor OS in patients with PC (HR=1.92, 95% CI=1.60-2.30, p<0.002). In addition, subgroup analysis indicated that increased mGPS remained a significant prognostic factor irrespective of the study design, region, disease status, treatment, survival analysis, cancer type, study center, or the Newcastle-Ottawa Scale (NOS) score (all p<0.05). There was a significant correlation between higher mGPS and male gender (Odds ratio [OR]=1.30, 95% CI=1.01-1.67, p=0.038). Elevated pretreatment mGPS is a marker of poor prognosis in patients with PC. As an easily available and cost-effective inflammatory parameter, mGPS can serve as a promising tool for prognostication in PC.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Neoplasias Pancreáticas , Albumina Sérica/metabolismo , Biomarcadores/análise , Proteína C-Reativa/análise , Humanos , Masculino , Neoplasias Pancreáticas/mortalidade , Prognóstico , Albumina Sérica/análise , Índice de Gravidade de Doença , Análise de Sobrevida
16.
Biol Psychiatry ; 89(6): 615-626, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33190845

RESUMO

BACKGROUND: Deficiency in neuronal structural plasticity is involved in the development of major depressive disorder. TWIST1, a helix-loop-helix transcription factor that is essential for morphogenesis and organogenesis, is normally expressed at low levels in mature neurons. However, it is poorly understood what role TWIST1 plays in the brain and whether it is involved in the pathophysiology of depression. METHODS: Depressive-like behaviors in C57BL/6J mice were developed by chronic social defeat stress. Genetic and pharmacological approaches were used to investigate the role of the TWIST1-miR-214-PPAR-δ signaling pathway in depressive-like behaviors. Molecular biological and morphological studies were performed to define the molecular mechanisms downstream of TWIST1. RESULTS: The expression of TWIST1 was positively correlated with depressive behaviors in humans and mice. Chronic stress elevated TWIST1 expression in the medial prefrontal cortex of mice, which was reversed by fluoxetine treatment. While the overexpression of TWIST1 increased susceptibility to stress, the knockdown of TWIST1 prevented the defective morphogenesis of dendrites of pyramidal neurons in layer II/III of the medial prefrontal cortex and alleviated depressive-like behaviors. Mechanistically, this prodepressant property of TWIST1 was mediated, at least in part, through the repression of miR-214-PPAR-δ signaling and mitochondrial function, which was also mimicked by genetic and pharmacological inhibition of PPAR-δ. CONCLUSIONS: These results suggest that TWIST1 in the medial prefrontal cortex mediates chronic stress-induced dendritic remodeling and facilitates the occurrence of depressive-like behavior, providing new information for developing drug targets for depression therapy.


Assuntos
Transtorno Depressivo Maior , Animais , Depressão , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Córtex Pré-Frontal , Estresse Psicológico , Fatores de Transcrição , Proteína 1 Relacionada a Twist
17.
Insect Sci ; 28(2): 363-376, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32091660

RESUMO

Fruit flies usually harbor diverse communities of bacteria in their digestive systems, which are known to play a significant role in their fitness. However, little information is available on Zeugodacus tau, a polyphagous pest worldwide. This study reports the first extensive analysis of bacterial communities in different life stages and their effect on the development and reproduction of laboratory-reared Z. tau. Cultured bacteria were identified using the conventional method, and all bacteria were identified by high-throughput technologies (16S ribosomal RNA gene sequencing of V3-V4 region). A total of six bacterial phyla were identified in larvae, pupae, and male and female adult flies, which were distributed into 14 classes, 32 orders, 58 families and 96 genera. Proteobacteria was the most represented phylum in all the stages except larvae. Enterobacter, Klebsiella, Providencia, and Pseudomonas were identified by conventional and next-generation sequencing analysis in both male and female adult flies, and Enterobacter was found to be the main genus. After being fed with antibiotics from the first instar larvae, bacterial diversity changed markedly in the adult stage. Untreated flies laid eggs and needed 20 days before oviposition while the treated flies showed ovary development inhibited and were not able to lay eggs, probably due to the alteration of the microbiota. These findings provide the cornerstone for unexplored research on bacterial function in Z. tau, which will help to develop an environmentally friendly management technique for this kind of harmful insect.


Assuntos
Bactérias/isolamento & purificação , Microbiota , Tephritidae/microbiologia , Tephritidae/fisiologia , Animais , Bactérias/classificação , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Larva/crescimento & desenvolvimento , Larva/microbiologia , Masculino , Óvulo/crescimento & desenvolvimento , Óvulo/microbiologia , Pupa/crescimento & desenvolvimento , Pupa/microbiologia , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Reprodução , Tephritidae/crescimento & desenvolvimento
18.
Brain Imaging Behav ; 15(3): 1655-1666, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32705467

RESUMO

CSF1R-related leukoencephalopathy is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few studies have investigated the intrinsic brain alternations of patients with CSF1R-related leukoencephalopathy. We aim to evaluate the structural and functional changes in those patients. Seven patients with CSF1R-related leukoencephalopathy and 15 age-matched healthy controls (HCs) underwent multimodal magnetic resonance imaging (MRI), including high-resolution T1-weighted imaging, T2-weighted fluid attenuated inversion recovery imaging, diffusion-weighted imaging, diffusion kurtosis imaging (DKI) and resting-state functional MRI. First, to detect structural alterations, the gray matter volumes were compared using voxel-based morphometry analyses. Second, DKI parametric maps were used to evaluate the white matter (WM) connectivity changes. Finally, we constructed a seed-based resting-state functional connectivity matrix based on 90 regions of interest and examined the functional network changes of CSF1R-related leukoencephalopathy. Unlike the HCs, patients with CSF1R-related leukoencephalopathy predominantly had morphological atrophy in the bilateral thalamus and left hippocampus. In addition, the abnormal diffusivity was mainly distributed in the splenium of the corpus callosum, periventricular regions, centrum semiovale, subcortical U-fibers and midline cortex structures. Moreover, the patients had significantly reduced functional connectivity between the bilateral caudate nucleus and their contralateral hippocampus. Therefore, in addition to hyperintensity on the T2-weighted images, CSF1R-related leukoencephalopathy also showed abnormal structural and functional alterations, including subcortical atrophy and reduced functional connectivity, as well as altered diffuse parameters in the WM and subcortical regions. These findings expand our understanding of the potential pathophysiologic mechanism behind this hereditary disease.


Assuntos
Leucoencefalopatias , Substância Branca , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Imageamento por Ressonância Magnética , Substância Branca/diagnóstico por imagem
19.
Can Assoc Radiol J ; 72(3): 404-409, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32391717

RESUMO

PURPOSE: Owing to the increasing average age of first-time mothers, as well as advances in assistive reproductive technology, the number of hysterosalpingography (HSG) requests has continued to rise. This increases the likelihood of patients presenting with unsuspected early pregnancies prior to HSG. Currently, there is no standard of practice for the pre-procedural screening of pregnancy prior to HSG, with most institutions using patient-reported pregnancy status and unreliable menstrual cycle dating methods. We implemented a multi-institutional pre-procedural pregnancy screening protocol in order to determine the rate of unsuspected pregnancies prior to HSG and improve the quality and safety of these procedures. METHODS: Following multi-institutional and multidisciplinary input, a consensus protocol was formulated and implemented across 9 institutions in the Lower Mainland of British Columbia, Canada. Subsequent tracking of pregnancy testing was then performed over a period of 3 years. RESULTS: Pre-implementation review of protocols demonstrated large disparities between institutions. A total of 6333 HSG examinations were scheduled in the review period following implementation. Of these, 10 patients were found to have positive pregnancy tests (0.16%), despite self-reporting that they were not pregnant or had recent menstrual bleeding. DISCUSSION: Hysterosalpingography is contraindicated in pregnancy, yet we identified 10 unsuspected pregnancies in patients who would have otherwise undergone HSG examinations with existing guidelines. While there remains insufficient data on the deleterious effects of performing HSG on an unsuspected pregnancy, the potential physical, economical, and psychosocial consequences of performing an HSG during pregnancy are sufficient to merit consideration of relatively inexpensive routine pregnancy screening prior to HSG.


Assuntos
Histerossalpingografia , Testes de Gravidez , Gravidez , Adulto , Protocolos Clínicos , Contraindicações de Procedimentos , Feminino , Humanos , Histerossalpingografia/métodos , Estudos Retrospectivos , Adulto Jovem
20.
Seizure ; 84: 47-52, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33278788

RESUMO

BACKGROUND: Mutations in the IRF2BPL gene can cause neurodevelopmental disorders. We describe the clinical and genetic characteristics of a Chinese patient with a novel abnormality in this gene, explore the potential pathogenic mechanism and summarize the clinical characteristics of 25 patients with IRF2BPL mutations. METHODS: We identified the gene mutation sites by whole-exome and Sanger sequencing. The protein-protein interaction network of the IRF2BPL gene was constructed using bioinformatic techniques, and its function was enriched. We conducted a functional experiment to explore the potential pathogenicity of the identified IRF2BPL gene mutation. RESULTS: An 8-year-old girl presented with progressive cerebellar ataxia, including involuntary tremor and slurred speech. Electroencephalography and electromyography revealed no abnormalities. Structural cranial MRI was also normal, but genetic analysis identified a truncating de novo variant in IRF2BPL. Bioinformatics predicted that IRF2BPL would be associated with IRF2 and 10 other genes and involved in ubiquitin binding and other pathways. The cellular location of IRF2BPL was altered, and compared to control cells, the level of ubiquitinated proteins was significantly decreased in cells harbouring the mutation. CONCLUSION: In this study, we identified a truncating de novo variant of IRF2BPL as a causative gene in the neurodevelopmental disorder of a Chinese girl. Impairment of the ubiquitin-proteasome pathway caused by this IRF2BPL mutation may play an important role in this neurodevelopmental disorder.


Assuntos
Transtornos do Neurodesenvolvimento , Proteínas de Transporte/genética , Criança , Eletroencefalografia , Feminino , Humanos , Mutação/genética , Transtornos do Neurodesenvolvimento/genética , Proteínas Nucleares/genética , Sequenciamento Completo do Exoma
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