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1.
Artigo em Inglês | MEDLINE | ID: mdl-33221327

RESUMO

BACKGROUND: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms. METHODS: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14. RESULTS: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003). CONCLUSIONS: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores.

2.
Nat Commun ; 11(1): 5717, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177521

RESUMO

While the yeast Chz1 acts as a specific histone-chaperone for H2A.Z, functions of CHZ-domain proteins in multicellular eukaryotes remain obscure. Here, we report on the functional characterization of OsChz1, a sole CHZ-domain protein identified in rice. OsChz1 interacts with both the canonical H2A-H2B dimer and the variant H2A.Z-H2B dimer. Within crystal structure the C-terminal region of OsChz1 binds H2A-H2B via an acidic region, pointing to a previously unknown recognition mechanism. Knockout of OsChz1 leads to multiple plant developmental defects. At genome-wide level, loss of OsChz1 causes mis-regulations of thousands of genes and broad alterations of nucleosome occupancy as well as reductions of H2A.Z-enrichment. While OsChz1 associates with chromatin regions enriched of repressive histone marks (H3K27me3 and H3K4me2), its loss does not affect the genome landscape of DNA methylation. Taken together, it is emerging that OsChz1 functions as an important H2A/H2A.Z-H2B chaperone in dynamic regulation of chromatin for higher eukaryote development.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33199628

RESUMO

Nucleosome Assembly Protein 1 (NAP1) family proteins are evolutionarily conserved histone chaperones that play important roles in diverse biological processes. In this study, we determined the crystal structure of Arabidopsis NAP1-Related Protein 1 (NRP1) complexed with H2A-H2B and uncovered a previously unknown interaction mechanism in histone chaperoning. Both in vitro binding and in vivo plant rescue assays proved that interaction mediated by the N-terminal α-helix (αN) domain is essential for NRP1 function. In addition, the C-terminal acidic domain (CTAD) of NRP1 binds to H2A-H2B through a conserved mode similar to other histone chaperones. We further extended previous knowledge of the NAP1-conserved earmuff domain by mapping the amino acids of NRP1 involved in association with H2A-H2B. Finally, we showed that H2A-H2B interactions mediated by αN, earmuff, and CTAD domains are all required for the effective chaperone activity of NRP1. Collectively, our results reveal multiple interaction modes of a NAP1 family histone chaperone and shed light on how histone chaperones shield H2A-H2B from nonspecific interaction with DNA.

4.
BMC Musculoskelet Disord ; 21(1): 740, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183264

RESUMO

BACKGROUND: There is a paucity of reports clarifying the implication of knee osteoarthritis (OA) on spinal sagittal alignment of patients undergone surgery for lumbar spine. This study aimed to analyze how osteoarthritic knee affects radiographic and clinical results of degenerative lumbar disease patients undergone lumbar fusion. METHODS: We retrospectively reviewed the medical records and radiographs of 74 consecutive degenerative lumbar disease patients who underwent posterior instrumentation and fusion surgery between May 2016 and June 2017 and were followed up for minimum 3 years postoperatively. The patients were divided into 2 groups according to the severity of knee OA by Kellgren-Lawrence grading (KLG) scale (group I, KLG 1 or 2 [n = 39]; group II, KLG 3 or 4 [n = 35]). Patient demographic data, comorbidities, spinal sagittal parameters and clinical scores were extracted and compared at preoperative, postoperative 1 month and the ultimate follow-up between the groups. In radiographic assessment, sagittal alignment parameters and sagittal balance were used. In clinical assessment, the scores of Oswestry disability index (ODI) and Scoliosis Research Society questionnaire (SRS-22) were used. For the frequency analysis of categorical variables across the groups, chi-square test was used and student t tests was used to compare the differences of continuous variables. RESULTS: In radiographic assessment, TLK (thoracolumbar kyphosis), LL (lumbar lordosis), PT (pelvic tilt), C7 SVA (sagittal vertical axis) in both groups improved significantly after surgery (p <  0.05). However, LL, PT, C7SVA improved at postoperative 1 month in the group II were not maintained at the ultimate postoperative follow-up. In clinical assessment, preoperative Oswestry disability index (ODI, %) and all SRS-22 subscores of the group I and II were not different (p > 0.05). There were significant differences between the groups at the ultimate follow-up in ODI (- 25.6 vs - 12.1, p <  0.001), SRS total score (%) (28 vs 20, p = 0.037), function subscore (1.4 vs 0.7, p = 0.016), and satisfaction subscore (1.6 vs 0.6, p < 0.001). CONCLUSION: Osteoarthritic knee with KLG 3 or 4 have a negative influence on maintaining postoperative spinal sagittal alignment, balance, and the clinical outcomes achieved immediately by posterior instrumentation and fusion for lumbar degenerative disease. TRIAL REGISTRATION: This study was retrospectively registered with approval by the institutional review board (IRB) of our institution (approval number: 2018-11-007).

5.
BMC Med ; 18(1): 278, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054810

RESUMO

BACKGROUND: Childhood trauma increases the risk for adult obesity through multiple complex pathways, and the neural substrates are yet to be determined. METHODS: Participants from three population-based neuroimaging cohorts, including the IMAGEN cohort, the UK Biobank (UKB), and the Human Connectome Project (HCP), were recruited. Voxel-based morphometry analysis of both childhood trauma and body mass index (BMI) was performed in the longitudinal IMAGEN cohort; validation of the findings was performed in the UKB. White-matter connectivity analysis was conducted to study the structural connectivity between the identified brain region and subdivisions of the hypothalamus in the HCP. RESULTS: In IMAGEN, a smaller frontopolar cortex (FPC) was associated with both childhood abuse (CA) (ß = - .568, 95%CI - .942 to - .194; p = .003) and higher BMI (ß = - .086, 95%CI - .128 to - .043; p < .001) in male participants, and these findings were validated in UKB. Across seven data collection sites, a stronger negative CA-FPC association was correlated with a higher positive CA-BMI association (ß = - 1.033, 95%CI - 1.762 to - .305; p = .015). Using 7-T diffusion tensor imaging data (n = 156), we found that FPC was the third most connected cortical area with the hypothalamus, especially the lateral hypothalamus. A smaller FPC at age 14 contributed to higher BMI at age 19 in those male participants with a history of CA, and the CA-FPC interaction enabled a model at age 14 to account for some future weight gain during a 5-year follow-up (variance explained 5.8%). CONCLUSIONS: The findings highlight that a malfunctioning, top-down cognitive or behavioral control system, independent of genetic predisposition, putatively contributes to excessive weight gain in a particularly vulnerable population, and may inform treatment approaches.

6.
Biosci Rep ; 40(9)2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32896857

RESUMO

The molecular weight of the polysaccharide and the chemical groups it contains has an important influence on its biological activity, relatively low molecular weight polysaccharides may have better antioxidant activity. Polysaccharides isolated from the fruiting bodies of Morchella sextelata (MSP) were treated by γ-irradiation at 10, 100 and 1000 kGy doses, and the physicochemical properties and antioxidant activity of irradiated MSP were investigated. Microscopic observation under a scanning electron microscope (SEM) showed that breakage and pores appeared on the surface of the irradiated polysaccharide. As the irradiation dose increased, the average molecular weight of MSP decreased significantly, while the particle size and thermal stability of MSP first increased at 10 and 100 kGy doses and then decreased at 1000 kGy doses. The antioxidant activities, measured by free radical scavenging tests and protective effect on PC12 cells injured by H2O2, were all increased after irradiation, especially when the concentration of MSP was low (50 and 100 µg/ml). Therefore, irradiation treatment was an effective method to enhance the activity of polysaccharides.

7.
EBioMedicine ; 58: 102910, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32739867

RESUMO

BACKGROUND: Abnormalities of functional activation and cortical volume in brain regions involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of social anxiety disorder (SAD). However, few studies have performed separate measurements of cortical thickness (CT) and cortical surface area (CSA) which reflect different neurobiological processes. Thus, we aimed to explore the cortical morphological anomaly separately in SAD using FreeSurfer. METHODS: High-resolution structural magnetic resonance images were obtained from 32 non-comorbid never-treated adult SAD patients and 32 demography-matched healthy controls. Cortical morphometry indices including CT and CSA were separately determined by FreeSurfer and compared between the two groups via whole-brain vertex-wise analysis, while partial correlation analysis using age and gender as covariates were conducted. FINDINGS: The patients with SAD showed decreased CT but increased CSA near-symmetrically in the bilateral prefrontal cortex (PFC) of the dorsolateral, dorsomedial, and ventromedial subdivisions, as well as the right lateral orbitofrontal cortex; increased CSA in the left superior temporal gyrus (STG) was also observed in SAD. The CSA in the left PFC was negatively correlated with the disease duration. INTERPRETATION: As the balloon model hypothesis suggests that the tangentially stretched cortex may cause dissociations in cortical morphometry and affect the cortical capacity for information processing, our findings of dissociated morphological alterations in the PFC and cortical expansion in the STG may reflect the morphological alterations of the functional reorganization in those regions, and highlight the important role of those structures in the pathophysiology and neurobiology of SAD. FUNDING: This study was funded by the National Natural Science Foundation of China (Grant Nos. 31700964, 31800963, 81621003, and 81820108018).

8.
BMC Urol ; 20(1): 134, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859184

RESUMO

BACKGROUND: Primary small cell carcinoma of the bladder (SCCB) is a rare disease of the genitourinary tract and reported limitedly. SCCB is very aggressive and always mixed with other histologic components, but coexistence of SCCB and prostate adenocarcinoma is extremely rare. CASES PRESENTATION: Two aged males (72 and 58 years) were included in this study. Both of them presented with gross hematuria as initial symptom. Magnetic resonance imaging (MRI) demonstrated protruding lesions in the urinary bladder. Pathological examination after radical cystectomy and prostatectomy showed the concurrence of SCCB and prostate adenocarcinoma. One patient died of liver and lung metastasis 8 months after surgery, and the other patient was still alive after 19 months of follow-up. CONCLUSION: In this paper, we reported two unusual cases of coexistence of SCCB and prostate adenocarcinoma, and reviewed relative literatures with respect to the epidemiology, clinical features, pathologic features, diagnosis, treatment and prognosis of SCCB.

9.
Urol J ; 2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-32798228

RESUMO

PURPOSE: To systematically analyze histopathologic features of pseudocapsule in small renal cell tumor (diameter≤4cm), assess the integrity of pseudocapsules by Computed Tomography (CT), and provide theoretical basis for the safety of nephron sparing surgery. MATERIALS AND METHODS: The pathological data of 116 patients who underwent surgery with clear cell renal cell carcinoma admitted from May 2010 to October 2017 were retrospectively analyzed. All patients underwent a CT scan of the abdomen including an unenhanced and triple-phase (arterial, nephrographic and excretory) post contrast series."All patients underwent a CT scan of the abdomen including an unenhanced and triple-phase (arterial, nephrographic and excretory) post contrast series."All patients underwent a CT scan of the abdomen including an unenhanced and triple-phase (arterial, nephrographic and excretory) post contrast seriesAll patients underwent a CT scan of the abdomen including an unenhanced and three-phase (arterial, nephrographic and excretory) post contrast series. Thorough gross examination and histological sections were used to determine the integrity of the pseudocapsule by two uropathologists. The consistency between pathological findings and CT imaging were evaluated by Kappa consistency test. RESULTS: The mean diameter of tumor was 3.0cm, range (2.6 ± 0.8) cm. On CT the pseudocapsule can present with one of the three following feathers:1) A regular and distinct halo; 2)lobulated clear margins;3) blurred margins. On histopathology, complete psuedocapsule was found in 85 tumors, incomplete psuedocapsule in 25 and no psuedocapsule was found in 6 tumors; CT scan findings demonstrated a regular halo in 82 tumors, lobulated clear margins in 26 and blurred margins in 8 tumors(Kappa=0.833,P=0.000). CONCLUSIONS: Most small renal cell tumors have an obvious psuedocapsule. Preoperative determination of the psuedocapsule's integrity is particularly important. CT scan can reliably evaluate the tumor margins and demonstrate the psuedocapsule when present. The imaging results are well correlated with the pathologic findings.

10.
Neuroimage Clin ; 28: 102377, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32805679

RESUMO

Triple network dysfunction theory of schizophrenia postulates that the interaction between the default-mode and the fronto-parietal executive network is disrupted by aberrant salience signals from the right anterior insula (rAI). To date, it is not clear how the proposed resting-state disruption translates to task-processing inefficiency in subjects with schizophrenia. Using a contiguous resting and 2-back task performance fMRI paradigm, we quantified the change in effective connectivity that accompanies rest-to-task state transition in 29 clinically stable patients with schizophrenia and 31 matched healthy controls. We found an aberrant task-evoked increase in the influence of the rAI to both executive (Cohen's d = 1.35, p = 2.8 × 10-6) and default-mode (Cohen's d = 1.22, p = 1.5 × 10-5) network regions occur in patients when compared to controls. In addition, the effective connectivity from middle occipital gyrus (dorsal visual cortex) to insula is also increased in patients as compared with healthy controls. Aberrant insula to executive network influence is pronounced in patients with more severe negative symptom burden. These findings suggest that control signals from rAI are abnormally elevated and directed towards both task-positive and task-negative brain regions, when task-related demands arise in schizophrenia. This aberrant, undiscriminating surge in salience signalling may disrupt contextually appropriate allocation of resources in the neuronal workspace in patients with schizophrenia.

11.
PLoS One ; 15(8): e0236470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750057

RESUMO

OBJECTIVES: Spinal cord injury (SCI) is associated with severe autonomic dysfunction. Patients with SCI often suffer from a lack of central nervous system control over the gastrointestinal system. Therefore, we hypothesized that patients with SCI would cause intestinal flora imbalance. We investigated alterations in the fecal microbiome in a group of patients with SCI. METHODS: Microbial communities in the feces of 23 patients and 23 healthy controls were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene. The relative abundances between the fecal microbiota at the genus level in patients with SCI and healthy individuals were determined using cluster analysis. RESULTS: The structure and quantity of fecal microbiota differed significantly between patients with SCI and healthy controls, but the richness and diversity were not significantly different. A two-dimensional heatmap showed that the relative abundances of forty-five operational taxonomic units (OTUs) were significantly enriched either in SCI or healthy samples. Among these, 18 OTUs were more abundant in healthy controls than in patients with SCI, and 27 OTUs were more abundant in the SCI group than in healthy controls. CONCLUSION: Our study showed that patients with SCI exhibited microbiome dysbiosis.


Assuntos
Disbiose/microbiologia , Fezes/microbiologia , Microbiota/genética , Traumatismos da Medula Espinal/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Disbiose/genética , Disbiose/patologia , Feminino , Microbioma Gastrointestinal/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Filogenia , RNA Ribossômico 16S/genética , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia
12.
Biomater Sci ; 8(16): 4595-4602, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32700684

RESUMO

Solid tumor cells in hypoxic regions resist chemotherapy treatment with conventional antitumor drugs (such as paclitaxel, PTX) because the inadequate O2 attenuates the intracellular generation of reactive oxygen species (ROS) and upregulates multidrug resistance protein expression. Hyperbaric O2 therapy concentrates on improving O2 delivery to the hypoxic tumor area, thereby enhancing the sensitivity of cancer cells to chemotherapy drugs. However, the implementation of this therapy often elicits immune response or potentiates toxicity of the drugs toward normal cells. In this work, we successfully fabricated RBC-based micro-vehicles for precise hypoxia-activated O2 delivery under the 980 nm laser irradiation. Interestingly, the subsequent chemotherapy of PTX for ovarian tumors was significantly enhanced owing to the alleviation of hypoxia tumor microenvironment. Meanwhile, the RBC-based micro-vehicles have low side tissue effects, superior biocompatibility, and ultra-low immune response. Overall, the RBC-based drug delivery system holds a fascinating perspective towards O2 delivery for chemotherapy enhancement in other clinical solid malignancies.

13.
J Integr Neurosci ; 19(2): 303-311, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706194

RESUMO

Cerebral ischemia-reperfusion injury is a common complication that occurs during stroke treatment. Increasingly, microRNAs have been found to participate in the modulation of neuron function; however, the role of microRNAs in cerebral ischemia-reperfusion injury remains unclear. We developed a mechanism of cerebral ischemia-reperfusion injury using a cellular model of oxygen-glucose deprivation and reoxygenation-induced injury in human neuroblastoma SH-SY5Y cells. We found that treatment of oxygen-glucose deprivation and reoxygenation promoted the apoptosis of SH-SY5Y cells. Analysis of microRNAs sequencing revealed that the expression of microRNA-27a-5p was induced, and microRNA-29b-3p expression was inhibited in neuroblastoma cells exposed to oxygen-glucose deprivation and reoxygenation. Either inhibition of microRNA-27a-5p or overexpression of microRNA-29b-3p mitigated oxygen-glucose deprivation and reoxygenation-induced cellular apoptosis. Bach1 was authenticated as a target gene of microRNA-27a-5p. Also, microRNA-27a-5p mediated the expression of Bach 1 along with its downstream signaling. N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine protected against oxygen-glucose deprivation and reoxygenation-induced apoptosis while decreasing miR-27a-5p expression and increasing microRNA-29b-3p expression. These results suggested that microRNA-27a-5p and microRNA-29b-3p may contribute to oxygen-glucose deprivation and reoxygenation-induced cellular injury. At the same time, N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine protects SH-SY5Y cells against oxygen-glucose deprivation and reoxygenation-induced injury partly through the inhibition of microRNA-27-a-5p and promotion of the Bach1/HO-1 signaling pathway.

14.
Microb Pathog ; 148: 104408, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32707310

RESUMO

Oxidative stress is implicated in the pathogenesis of influenza virus infection. Increasing evidences show that transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable non-selective cation channel, plays an important role in the pathomechanism of reactive oxygen species (ROS)-coupled diseases. The present study investigated the role of TRPM2 in pulmonary microvascular endothelial cells (PMVECs) during H9N2 influenza virus infection. We knocked down TRPM2 in PMVECs using TRPM2 shRNA lentiviral particles. Subsequently, we utilized enzyme-linked immunosorbent assay and flow cytometry to compare ROS levels, DNA damage, mitochondrial integrity, apoptosis, and inflammatory factors between control and TRPM2-knockdown PMVECs following H9N2 influenza virus infection. Inhibition of TRPM2 channels reduced H9N2 virus-induced intracellular ROS production, decreased DNA damage, and inhibited H9N2-induced cellular apoptosis. This study shows that the inhibition of TRPM2 channels may protect PMVECs from the damage caused by H9N2 virus infection. Our results highlight the importance of TRPM2 in modulating ROS production, apoptosis, mitochondrial dysfunction, cytokine expression, and DNA damage in H9N2 virus-infected PMVECs, and suggest that TRPM2 may be a potential antiviral target.

15.
Opt Lett ; 45(12): 3353-3356, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32538982

RESUMO

Periodically poled lithium niobate (PPLN) microcavities with additional reciprocal vectors attract attention as a platform for efficient parametric nonlinear optical processes with wavelength and polarization flexibility. Here, we report the simultaneous realization of multiple coupled parametric processes in PPLN microdisk cavities with dual periods as a result of the significantly increased number of reciprocal vectors to fulfill quasi-phase matchings for a series of nonlinear processes. PPLN microdisks with up to 1.43×105 quality factors and unit domain size of 90 nm in width were fabricated using CMOS compatible microfabrication techniques and electrically poled with the help of piezoresponse force microscopy. The conversion efficiency of second-harmonic signal was measured to be 51%W-1. Our work paves the way towards efficient cascaded parametric effects including third- and fourth-harmonic generations.

16.
Biol Psychiatry ; 88(6): 459-469, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414481

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) comorbid with sleep disturbances can produce profound disruption in daily life and negatively impact quality of life of both the child and the family. However, the temporal relationship between ADHD and sleep impairment is unclear, as are underlying common brain mechanisms. METHODS: This study used data from the Quebec Longitudinal Study of Child Development (n = 1601, 52% female) and the Adolescent Brain Cognitive Development Study (n = 3515, 48% female). Longitudinal relationships between symptoms were examined using cross-lagged panel models. Gray matter volume neural correlates were identified using linear regression. The transcriptomic signature of the identified brain-ADHD-sleep relationship was characterized by gene enrichment analysis. Confounding factors, such as stimulant drugs for ADHD and socioeconomic status, were controlled for. RESULTS: ADHD symptoms contributed to sleep disturbances at one or more subsequent time points in both cohorts. Lower gray matter volumes in the middle frontal gyrus and inferior frontal gyrus, amygdala, striatum, and insula were associated with both ADHD symptoms and sleep disturbances. ADHD symptoms significantly mediated the link between these structural brain abnormalities and sleep dysregulation, and genes were differentially expressed in the implicated brain regions, including those involved in neurotransmission and circadian entrainment. CONCLUSIONS: This study indicates that ADHD symptoms and sleep disturbances have common neural correlates, including structural changes of the ventral attention system and frontostriatal circuitry. Leveraging data from large datasets, these results offer new mechanistic insights into this clinically important relationship between ADHD and sleep impairment, with potential implications for neurobiological models and future therapeutic directions.

17.
Lab Invest ; 100(9): 1223-1237, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461588

RESUMO

MicroRNAs regulate gene expression at the posttranscriptional level, and this process has been shown to be implicated in the pathological processes of temporal lobe epilepsy. At present, studies about the impact of microRNA-181a (miR-181a) on epilepsy have focused on hippocampal neurons, and the effect of miR-181a on other cells in the hippocampus remains poorly understood. Herein, we explored the role of miR-181a-5p in a lithium-pilocarpine model of epilepticus in immature rats. We found that the hippocampal expression level of miR-181a-5p was increased. Inhibition of miR-181a-5p protected the hippocampus against epilepsy, including hippocampal insults, neuronal apoptosis, astrocyte and microglia activation, neuroinflammation, oxidative stress, mitochondrial function, and cognitive dysfunction. Moreover, miR-181a-5p inhibition exerted a seizure-suppressing effect via SIRT1 upregulation. Overall, our findings reveal the potential role of the miR-181a-5p/SIRT1 pathway in the development of temporal lobe epilepsy, and this pathway may represent a novel target for ameliorating epilepsy and its sequelae.

18.
Endocrine ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32419083

RESUMO

PURPOSE: To evaluate the safety and effectiveness of microwave ablation (MWA) versus lobectomy for the treatment of benign thyroid nodules > 4 cm. METHODS: We retrospectively analyzed the data of 48 patients who underwent MWA and 53 patients who underwent lobectomy to treat benign thyroid nodules > 4 cm. The patients were followed up for 12 months. The volume reduction ratio (VRR) was calculated. The operation time, incision length, hospitalization time, complications, thyroid function, symptoms, and cosmetic improvement were analyzed and compared between the two groups. RESULTS: During the 12-month follow-up, the mean nodule volume in the MWA group was reduced from 36.1 ± 23.1 to 4.0 ± 4.1 ml, and the mean VRR of the nodules was 90 ± 5% in the MWA group, which was comparable with that in the surgery group. No significant postoperative change in thyroid function was observed in the MWA group. Compared with the surgery group, the incidence of complications and postoperative pain in the MWA group were lower, the operation time, incision length, and hospitalization time in the MWA group were shorter, and satisfaction with the esthetic results in the MWA group was greater. CONCLUSION: MWA is safe and effective for the treatment of benign thyroid nodules > 4 cm. Moreover, MWA is associated with a faster recovery, fewer complications, better protection of thyroid function, and superior esthetic results relative to thyroid lobectomy.

19.
Am J Psychiatry ; 177(9): 844-854, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32375536

RESUMO

OBJECTIVE: The dual-pathway model has been proposed to explain the heterogeneity in symptoms of attention deficit hyperactivity disorder (ADHD) by two independent psychological pathways based on distinct brain circuits. The authors sought to test whether the hypothesized cognitive and motivational pathways have separable neural correlates. METHODS: In a longitudinal community-based cohort of 1,963 adolescents, the neuroanatomical correlates of ADHD were identified by a voxel-wise association analysis and then validated using an independent clinical sample (99 never-medicated patients with ADHD, 56 medicated patients with ADHD, and 267 healthy control subjects). The cognitive and motivational pathways were assessed by neuropsychological tests of working memory, intrasubject variability, stop-signal reaction time, and delay discounting. The associations were tested between the identified neuroanatomical correlates and both ADHD symptoms 2 years later and the polygenic risk score for ADHD. RESULTS: Gray matter volumes of both a prefrontal cluster and a posterior occipital cluster were negatively associated with inattention. Compared with healthy control subjects, never-medicated patients, but not medicated patients, had significantly lower gray matter volumes in these two clusters. Working memory and intrasubject variability were associated with the posterior occipital cluster, and delay discounting was independently associated with both clusters. The baseline gray matter volume of the posterior occipital cluster predicted the inattention symptoms in a 2-year follow-up and was associated with the genetic risk for ADHD. CONCLUSIONS: The dual-pathway model has both shared and separable neuroanatomical correlates, and the shared correlate in the occipital cortex has the potential to serve as an imaging trait marker of ADHD, especially the inattention symptom domain.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Sintomas Comportamentais , Cognição/fisiologia , Técnicas de Rastreamento Neuroanatômico/métodos , Lobo Occipital , Córtex Pré-Frontal , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/fisiopatologia , Ciências Biocomportamentais , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Estudos Longitudinais , Masculino , Motivação/fisiologia , Neuroimagem/métodos , Testes Neuropsicológicos , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/patologia , Tamanho do Órgão , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Medição de Risco/métodos
20.
Nanomedicine ; 28: 102198, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32334101

RESUMO

Failure of intraoperative detection, early minimal lesion and microscopic residual tumor margins elimination causes metastatic diffusion and lethal recurrence. However, during surgical process, surgeons can only rely largely on palpation and visual examination. Intraoperative bioimaging with the aid of the second near-infrared fluorescent (NIR II FL) light has entered the surgical excision area to bridge the gap of preoperative bioimaging and intraoperative resection. Here, we demonstrate that the follicle-stimulating hormone peptide (FSHP) engineered NIR II downshifting nanoparticles (DSNPs@FSHP) selectively undergo efficient ovarian tumor targeting property. Owing to the special biocompatibility of nanoprobes, this strategy provided rapid body clearance and efficient tumor targeting with significantly tumor to background (T/B) ratio enhanced for surgical excision. Based on these, this strategy can successfully empower the detection and surgical removal for both ovarian tumor lesions and ovarian tumor margins by NIR II FL bioimaging.

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