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1.
PLoS Biol ; 22(5): e3002596, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38718086

RESUMO

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early postnatal Katnal2 re-expression prevents ciliary, ventricular, and behavioral phenotypes in Katnal2-KO adults, suggesting a causal relationship and a potential treatment. Therefore, Katnal2 negatively regulates ependymal ciliary function and its deletion in mice leads to ependymal ciliary hyperfunction and hydrocephalus accompanying ASD-related behavioral, synaptic, and transcriptomic changes.


Assuntos
Transtorno do Espectro Autista , Cílios , Epêndima , Camundongos Knockout , Fenótipo , Animais , Cílios/metabolismo , Epêndima/metabolismo , Camundongos , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/fisiopatologia , Hidrocefalia/genética , Hidrocefalia/metabolismo , Hidrocefalia/patologia , Hidrocefalia/fisiopatologia , Hipocampo/metabolismo , Masculino , Neurônios/metabolismo , Camundongos Endogâmicos C57BL , Sinapses/metabolismo , Comportamento Animal , Katanina/metabolismo , Katanina/genética , Transcriptoma/genética , Modelos Animais de Doenças
2.
PLoS One ; 19(4): e0298278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38683769

RESUMO

PURPOSE: To investigate the common CT findings of high-grade (HG) PanIN and clinical effects in the remnant pancreas in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. MATERIALS AND METHODS: Two hundred fifty-one patients with surgically confirmed IPMNs (118 malignant [invasive carcinoma/high-grade dysplasia] and 133 benign [low-grade dysplasia]) were retrospectively enrolled. The grade of PanIN (233 absent/low-grade and 18 high-grade) was recorded, and all patients underwent serial CT follow-up before and after surgery. Two radiologists analyzed CT findings of high-risk stigmata or worrisome features according to 2017 international consensus guidelines. They also analyzed tumor recurrence on serial follow-up CT after surgery. Statistical analyses were performed to identify significant predictors and clinical impact on postoperative outcomes of HG PanIN. RESULTS: PanIN grade showed a significant association with IPMN grade (p = 0.012). Enhancing mural nodules ≥5 mm, abrupt main pancreatic duct (MPD) changes with distal pancreatic atrophy, increased mural nodule size and MPD diameter were common findings in HG PanIN (P<0.05). In multivariate analysis, abrupt MPD change with distal pancreatic atrophy (odds ratio (OR) 6.59, 95% CI: 2.32-18.72, <0.001) and mural nodule size (OR, 1.05; 95% CI, 1.02-1.08, 0.004) were important predictors for HG PanIN. During postoperative follow-up, HG PanIN (OR, 4.98; 95% CI, 1.22-20.33, 0.025) was significantly associated with cancer recurrence in the remnant pancreas. CONCLUSION: CT can be useful for predicting HG PanIN using common features, such as abrupt MPD changes and mural nodules. In HG PanIN, extra caution is needed to monitor postoperative recurrence during follow-up.


Assuntos
Neoplasias Pancreáticas , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Gradação de Tumores , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Intraductais Pancreáticas/cirurgia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Adulto , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma in Situ/patologia , Carcinoma in Situ/diagnóstico por imagem , Carcinoma in Situ/cirurgia
3.
Med Res Rev ; 44(3): 897-918, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38084636

RESUMO

Fe-based nanostructures have possessed promising properties that make it suitable for chiral sensing and imaging applications owing to their ultra-small size, non-toxicity, biocompatibility, excellent photostability, tunable fluorescence, and water solubility. This review summarizes the recent research progress in the field of Fe-based nanostructures and places special emphases on their applications in chiral sensing and imaging. The synthetic strategies to prepare the targeted Fe-based structures were also introduced. The chiral sensing and imaging applications of the nanostructures are discussed in details.


Assuntos
Nanoestruturas , Pontos Quânticos , Humanos , Pontos Quânticos/química , Nanoestruturas/química , Diagnóstico por Imagem , Fluorescência , Solubilidade
4.
AJR Am J Roentgenol ; 222(2): e2330156, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37991335

RESUMO

BACKGROUND. Contrast-enhanced ultrasound (CEUS) with perfluorobutane has used varying protocols and diagnostic criteria for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of this article was to assess diagnostic performance for HCC of CEUS with perfluorobutane in high-risk patients using various criteria. METHODS. This retrospective post hoc study evaluating individual patient data from three earlier prospective studies from one hospital included 204 patients (136 men, 68 women; mean age, 63 ± 11 [SD] years) at high risk of HCC with 213 liver observations. Patients underwent CEUS using perfluorobutane from March 2019 to June 2022. Three radiologists (the examination's operator and two subsequent reviewers) independently interpreted examinations, assessing arterial, portal venous (arterial phase completion through 2 minutes), transitional (2-5 minutes after injection), and Kupffer (≥ 10 minutes after injection) phase findings. Six criteria for HCC were tested: 1, any arterial phase hyperenhancement (APHE) with Kupffer phase hypoenhancement; 2, nonrim APHE with Kupffer phase hypoenhancement; 3, nonrim APHE with portal venous washout; 4, nonrim APHE with portal venous washout and/or Kupffer phase hypoenhancement; 5, nonrim APHE with portal venous and/or transitional washout; 6, nonrim APHE with any of portal venous washout, transitional washout, or Kupffer phase hypoenhancement. Depending on the criteria, observations were instead deemed to be a non-HCC malignancy if showing rim APHE, early washout (at < 1 minute), or marked washout (at 2 minutes). Reference was pathology for malignant observations and pathology or imaging follow-up for benign observations. Diagnostic performance was assessed, pooling readers' data. RESULTS. Criterion 1 (no recognized features of non-HCC malignancy) had highest sensitivity (86.9%) but lowest specificity (43.2%) for HCC. Compared with nonrim APHE and portal venous washout (criterion 3), the addition of Kupffer phase hypoenhancement (criterion 4), transitional washout (criterion 5), or either feature (criterion 6) significantly increased sensitivity (34.4% vs 62.6-64.2%) and accuracy (61.8% vs 75.1-76.5%), but significantly decreased specificity (98.5% vs 91.9-94.1%). Criteria 2, 4, 5, and 6 (all incorporating transitional washout and/or Kupffer phase hypoenhancement) showed no significant differences in sensitivity (62.6-64.2%), specificity (91.9-94.1%), or accuracy (75.1-76.5%). CONCLUSION. Recognition of features of non-HCC malignancy improved specificity for HCC. Incorporation of the findings of transitional washout and/or Kupffer phase hypoenhancement improved sensitivity and accuracy, albeit lowered specificity, versus arterial and portal venous findings alone, without further performance variation among criteria incorporating those two findings. CLINICAL IMPACT. Kupffer phase acquisition may be optional for observations classified as HCC or non-HCC malignancy by arterial, portal venous, and transitional phases.


Assuntos
Carcinoma Hepatocelular , Fluorocarbonos , Neoplasias Hepáticas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Estudos Prospectivos , Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade , Ultrassonografia/métodos
5.
Medicine (Baltimore) ; 102(43): e35103, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37904476

RESUMO

Aberrant regulation of the long non-coding RNA SRY-box transcription factor 2 overlapping transcript (SOX2OT) has been reported in various diseases including gastric cancer (GC). However, an association between the well-studied rs9839776 single nucleotide polymorphism in SOX2OT and GC susceptibility has not been reported. This study aimed to evaluate the association between the rs9839776 single nucleotide polymorphism in SOX2OT and GC risk. Genotyping of rs9839776 was conducted using TaqMan genotyping assay for 460 patients with GC and 386 controls. We found that the dominant model (CT+TT) and rs9839776 T allele were significantly associated with decreased GC risk (P = .046, adjusted odds ratio [AOR] = 0.72, 95% confidence interval [CI] = 0.52-1.00 and P = .044, AOR = 0.74, 95% CI = 0.56-0.99, respectively). In addition, stratified analysis revealed that the dominant model (CT+TT) and rs9839776 T allele were significantly associated with decreased risk of lymph node metastasis-negative (P = .039, AOR = 0.67, 95% CI = 0.46-0.98 and P = .049, AOR = 0.71, 95% CI = 0.51-1.00, respectively) and tumor stage I (A+B)/II (A+B+C) (P = .028, AOR = 0.66, 95% CI = 0.50-0.96 and P = .041, AOR = 0.71, 95% CI = 0.52-0.99, respectively) GC. Our findings suggest that the rs9839776 T allele may be a protective factor against GC susceptibility. Further research is needed to clarify whether rs9839776 affects SOX2OT expression.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Fatores de Proteção , República da Coreia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/patologia
6.
Korean J Radiol ; 24(10): 983-995, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37793669

RESUMO

OBJECTIVE: To compare the diagnostic performance and interobserver agreement between contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CE-MRI) with magnetic resonance cholangiopancreatography (MRCP) for evaluating the resectability in patients with extrahepatic cholangiocarcinoma (eCCA). MATERIALS AND METHODS: This retrospective study included treatment-naïve patients with pathologically confirmed eCCA, who underwent both CECT and CE-MRI with MRCP using extracellular contrast media between January 2015 and December 2020. Among the 214 patients (146 males; mean age ± standard deviation, 68 ± 9 years) included, 121 (56.5%) had perihilar cholangiocarcinoma. R0 resection was achieved in 108 of the 153 (70.6%) patients who underwent curative-intent surgery. Four fellowship-trained radiologists independently reviewed the findings of both CECT and CE-MRI with MRCP to assess the local tumor extent and distant metastasis for determining resectability. The pooled area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of CECT and CE-MRI with MRCP were compared using clinical, surgical, and pathological findings as reference standards. The interobserver agreement of resectability was evaluated using Fleiss kappa (κ). RESULTS: No significant differences were observed between CECT and CE-MRI with MRCP in the pooled AUC (0.753 vs. 0.767), sensitivity (84.7% [366/432] vs. 90.3% [390/432]), and specificity (52.6% [223/424] vs. 51.4% [218/424]) (P > 0.05 for all). The AUC for determining resectability was higher when CECT and CE-MRI with MRCP were reviewed together than when CECT was reviewed alone in patients with discrepancies between the imaging modalities or with indeterminate resectability (0.798 [0.754-0.841] vs. 0.753 [0.697-0.808], P = 0.014). The interobserver agreement for overall resectability was fair for both CECT (κ = 0.323) and CE-MRI with MRCP (κ = 0.320), without a significant difference (P = 0.884). CONCLUSION: CECT and CE-MRI with MRCP showed no significant differences in the diagnostic performance and interobserver agreement in determining the resectability in patients with eCCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Masculino , Humanos , Colangiopancreatografia por Ressonância Magnética/métodos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos
7.
Mol Psychiatry ; 28(11): 4642-4654, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37730842

RESUMO

Dopamine (DA) neurons in the ventral tegmental area (VTA) promote social brain functions by releasing DA onto nucleus accumbens neurons, but it remains unclear how VTA neurons communicate with cortical neurons. Here, we report that the medial prefrontal cortex (mPFC)-lateral hypothalamus (LH)-VTA pathway contributes to social deficits in mice with IRSp53 deletion restricted to cortical excitatory neurons (Emx1-Cre;Irsp53fl/fl mice). LH-projecting mutant mPFC neurons display abnormally increased excitability involving decreased potassium channel gene expression, leading to excessive excitatory synaptic input to LH-GABA neurons. A circuit-specific IRSp53 deletion in LH-projecting mPFC neurons also increases neuronal excitability and induces social deficits. LH-GABA neurons with excessive mPFC excitatory synaptic input show a compensatory decrease in excitability, weakening the inhibitory LHGABA-VTAGABA pathway and subsequently over-activating VTA-GABA neurons and over-inhibiting VTA-DA neurons. Accordingly, optogenetic activation of the LHGABA-VTAGABA pathway improves social deficits in Emx1-Cre;Irsp53fl/fl mice. Therefore, the mPFC-LHGABA-VTAGABA-VTADA pathway contributes to the social deficits in Emx1-Cre;Irsp53fl/fl mice.


Assuntos
Região Hipotalâmica Lateral , Área Tegmentar Ventral , Animais , Camundongos , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Ácido gama-Aminobutírico/metabolismo , Região Hipotalâmica Lateral/metabolismo , Núcleo Accumbens/metabolismo , Área Tegmentar Ventral/metabolismo
9.
Ultrasound Med Biol ; 49(10): 2256-2263, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37495497

RESUMO

OBJECTIVE: The aim of the work described here was to evaluate the diagnostic performance of perfluorobutane (PFB)-enhanced ultrasound in differentiating hepatocellular carcinoma (HCC) from non-HCC malignancies and other benign lesions using different acquisition methods. METHODS: This prospective study included 69 patients with solid liver lesions larger than 1 cm who were scheduled for biopsy or radiofrequency ablation between September 2020 and March 2021. Lesion diagnosis was designated by three blinded radiologists after reviewing three different sets of acquired images selected according to the following presumed acquisition methods: (i) method A, acquisition up to 5 min after contrast injection; (ii) method B, acquisition up to 1 min after contrast injection with additional Kupffer phase; and (iii) method C, acquisition up to 5 min after contrast injection with additional Kupffer phase. RESULTS: After excluding 7 technical failures, 62 patients with liver lesions (mean size: 24.2 ± 14.8 mm), which consisted of 7 benign lesions, 37 non-HCC malignancies and 18 HCCs. For the HCC diagnosis, method C had the highest sensitivity (75.9%), followed by method B (72.2%) and method A (68.5%), but failed to exhibit statistical significance (p = 0.12). There was no significant difference with respect to the pooled specificity between the three methods (p = 0.28). Diagnostic accuracy was the highest with method C (87.1%) but failed to exhibit statistical significance (p = 0.24). CONCLUSION: Image acquisition up to 5 min after contrast injection with additional Kupffer phase could potentially result in high accuracy and sensitivity without loss of specificity in diagnosing HCC with PFB-enhanced ultrasound.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Prospectivos , Meios de Contraste , Ultrassonografia/métodos , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade , Estudos Retrospectivos
10.
Ultrasonography ; 42(4): 479-489, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37423603

RESUMO

Contrast-enhanced ultrasonography (CEUS) is a noninvasive imaging modality used to diagnose hepatocellular carcinoma (HCC) based on specific imaging features, without the need for pathologic confirmation. Two types of ultrasound contrast agents are commercially available: pure intravascular agents (such as SonoVue) and Kupffer agents (such as Sonazoid). Major guidelines recognize CEUS as a reliable imaging method for HCC diagnosis, although they differ depending on the contrast agents used. The Korean Liver Cancer Association-National Cancer Center guideline includes CEUS with either SonoVue or Sonazoid as a second-line diagnostic technique. However, Sonazoid-enhanced ultrasound is associated with several unresolved issues. This review provides a comparative overview of these contrast agents regarding pharmacokinetic features, examination protocols, diagnostic criteria for HCC, and potential applications in the HCC diagnostic algorithm.

11.
ACS Appl Mater Interfaces ; 15(29): 34779-34788, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37431988

RESUMO

The rational synthesis and tailoring of metal-organic frameworks (MOFs) with multifunctional micro/nanoarchitectures have emerged as a subject of significant academic interest owing to their promising potential for utilization in advanced energy storage devices. Herein, we explored a category of three-dimensional (3D) NiCo2S4 nanospikes that have been integrated into a 1D Fe3C microarchitecture using a chemical surface transformation process. The resulting electrode materials, i.e., Fe3C@NiCo2S4 nanospikes, exhibit immense potential for utilization in high-performance hybrid supercapacitors. The nanospikes exhibit an elevated specific capacity (1894.2 F g-1 at 1 A g-1), enhanced rate capability (59%), and exceptional cycling stability (92.5% with 98.7% Coulombic efficiency) via a charge storage mechanism reminiscent of a battery. The augmented charge storage characteristics are attributed to the collaborative features of the active constituents, amplified availability of active sites inherent in the nanospikes, and the proficient redox chemical reactions of multi-metallic guest species. When using nitrogen-doped carbon nanofibers as the anode to fabricate hybrid supercapacitors, the device exhibits high energy and power densities of 62.98 Wh kg-1 and 6834 W kg-1, respectively, and shows excellent long-term cycling stability (95.4% after 5000 cycles), which affirms the significant potential of the proposed design for applications in hybrid supercapacitors. The DFT study showed the strong coupling of the oxygen from the electrolyte OH- with the metal atom of the nanostructures, resulting in high adsorption properties that facilitate the redox reaction kinetics.

12.
Korean J Radiol ; 24(6): 482-497, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37271203

RESUMO

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiologia , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Ultrassonografia/métodos , Meios de Contraste , República da Coreia
13.
Nat Commun ; 14(1): 3547, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37321992

RESUMO

Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and juvenile seizure-related death. Ank2-cKO cortical neurons show abnormally increased excitability and firing rate. These changes accompanied decreases in the total level and function of the Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels and the density of these channels in the enlengthened axon initial segment. Importantly, the Kv7 agonist, retigabine, rescued neuronal excitability, juvenile seizure-related death, and hyperactivity in Ank2-cKO mice. These results suggest that Ank2 regulates neuronal excitability by regulating the length of and Kv7 density in the AIS and that Kv7 channelopathy is involved in Ank2-related brain dysfunctions.


Assuntos
Epilepsia , Canais de Potássio KCNQ , Animais , Camundongos , Epilepsia/metabolismo , Canais de Potássio KCNQ/genética , Canal de Potássio KCNQ2/genética , Canal de Potássio KCNQ2/metabolismo , Canal de Potássio KCNQ3/metabolismo , Neurônios/metabolismo , Convulsões/genética , Convulsões/metabolismo
14.
Cells ; 12(11)2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37296585

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that are among the most appealing candidates for regenerative medicine and may aid in the repair and regeneration of skeletal disorders through multiple mechanisms, including angiogenesis, differentiation, and response to inflammatory conditions. Tauroursodeoxycholic acid (TUDCA) has recently been used in various cell types as one of these drugs. The mechanism of osteogenic differentiation by TUDCA in hMSCs remains unknown. METHODS: Cell proliferation was performed by the WST-1 method, and alkaline phosphatase activity and alizarin red-sulfate staining were used to confirm the osteogenic differentiation indicator. Expression of genes related to bone differentiation and specific genes related to signaling pathways was confirmed by quantitative real-time polymerase chain reaction. RESULTS: We found that cell proliferation was higher as the concentration increased, and showed that the induction of osteogenic differentiation was significantly enhanced. We also show that osteogenic differentiation genes were upregulated, with the expression of the epidermal growth factor receptor (EGFR) and cAMP responsive element binding protein 1 (CREB1) being specifically high. To confirm the participation of the EGFR signaling pathway, the osteogenic differentiation index and expression of osteogenic differentiation genes were determined after using an EGFR inhibitor. As a result, EGFR expression was remarkably low, and that of CREB1, cyclin D1, and cyclin E1 was also significantly low. CONCLUSIONS: Therefore, we suggest that TUDCA-induced osteogenic differentiation of human MSCs is enhanced through the EGFR/p-Akt/CREB1 pathway.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Humanos , Osteogênese/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Diferenciação Celular/genética , Receptores ErbB/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
15.
Mol Psychiatry ; 28(8): 3548-3562, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37365244

RESUMO

ADNP syndrome, involving the ADNP transcription factor of the SWI/SNF chromatin-remodeling complex, is characterized by developmental delay, intellectual disability, and autism spectrum disorders (ASD). Although Adnp-haploinsufficient (Adnp-HT) mice display various phenotypic deficits, whether these mice display abnormal synaptic functions remain poorly understood. Here, we report synaptic plasticity deficits associated with cognitive inflexibility and CaMKIIα hyperactivity in Adnp-HT mice. These mice show impaired and inflexible contextual learning and memory, additional to social deficits, long after the juvenile-stage decrease of ADNP protein levels to ~10% of the newborn level. The adult Adnp-HT hippocampus shows hyperphosphorylated CaMKIIα and its substrates, including SynGAP1, and excessive long-term potentiation that is normalized by CaMKIIα inhibition. Therefore, Adnp haploinsufficiency in mice leads to cognitive inflexibility involving CaMKIIα hyperphosphorylation and excessive LTP in adults long after its marked expressional decrease in juveniles.


Assuntos
Transtorno Autístico , Deficiência Intelectual , Camundongos , Animais , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal/genética , Potenciação de Longa Duração/genética , Transtorno Autístico/metabolismo , Cognição , Proteínas de Homeodomínio/metabolismo
16.
Front Mol Neurosci ; 16: 1111388, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873104

RESUMO

Chd8+/N2373K mice with a human C-terminal-truncating mutation (N2373K) display autistic-like behaviors in juvenile and adult males but not in females. In contrast, Chd8+/S62X mice with a human N-terminal-truncating mutation (S62X) display behavioral deficits in juvenile males (not females) and adult males and females, indicative of age-differential sexually dimorphic behaviors. Excitatory synaptic transmission is suppressed and enhanced in male and female Chd8+/S62X juveniles, respectively, but similarly enhanced in adult male and female mutants. ASD-like transcriptomic changes are stronger in newborn and juvenile (but not adult) Chd8+/S62X males but in newborn and adult (not juvenile) Chd8+/S62X females. These results point to age-differential sexual dimorphisms in Chd8+/S62X mice at synaptic and transcriptomic levels, in addition to the behavioral level.

18.
Eur Radiol ; 33(5): 3660-3670, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36934202

RESUMO

OBJECTIVE: To investigate the image quality and lesion conspicuity of a deep-learning-based contrast-boosting (DL-CB) algorithm on double-low-dose (DLD) CT of simultaneous reduction of radiation and contrast doses in participants at high-risk for hepatocellular carcinoma (HCC). METHODS: Participants were recruited and underwent four-phase dynamic CT (NCT04722120). They were randomly assigned to either standard-dose (SD) or DLD protocol. All CT images were initially reconstructed using iterative reconstruction, and the images of the DLD protocol were further processed using the DL-CB algorithm (DLD-DL). The primary endpoint was the contrast-to-noise ratio (CNR), the secondary endpoint was qualitative image quality (noise, hepatic lesion, and vessel conspicuity), and the tertiary endpoint was lesion detection rate. The t-test or repeated measures analysis of variance was used for analysis. RESULTS: Sixty-eight participants with 57 focal liver lesions were enrolled (20 with HCC and 37 with benign findings). The DLD protocol had a 19.8% lower radiation dose (DLP, 855.1 ± 254.8 mGy·cm vs. 713.3 ± 94.6 mGy·cm, p = .003) and 27% lower contrast dose (106.9 ± 15.0 mL vs. 77.9 ± 9.4 mL, p < .001) than the SD protocol. The comparative analysis demonstrated that CNR (p < .001) and portal vein conspicuity (p = .002) were significantly higher in the DLD-DL than in the SD protocol. There was no significant difference in lesion detection rate for all lesions (82.7% vs. 73.3%, p = .140) and HCCs (75.7% vs. 70.4%, p = .644) between the SD protocol and DLD-DL. CONCLUSIONS: DL-CB on double-low-dose CT provided improved CNR of the aorta and portal vein without significant impairment of the detection rate of HCC compared to the standard-dose acquisition, even in participants at high risk for HCC. KEY POINTS: • Deep-learning-based contrast-boosting algorithm on double-low-dose CT provided an improved contrast-to-noise ratio compared to standard-dose CT. • The detection rate of focal liver lesions was not significantly differed between standard-dose CT and a deep-learning-based contrast-boosting algorithm on double-low-dose CT. • Double-low-dose CT without a deep-learning algorithm presented lower CNR and worse image quality.


Assuntos
Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Neoplasias Hepáticas/diagnóstico por imagem , Estudos Prospectivos , Método Duplo-Cego , Doses de Radiação , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos
19.
Liver Transpl ; 29(5): 497-507, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36738083

RESUMO

Several major transplantation centers have used composite multimodality evaluation for the preoperative evaluation of potential living liver donors. This approach can be time-consuming and, although rare, can cause complications. We aimed to demonstrate the clinical feasibility of our comprehensive preoperative MR protocol for the preoperative assessment of living liver donor candidates instead of composite multimodality evaluation. Thirty-five consecutive living liver donor candidates underwent multiphasic liver CT and comprehensive donor protocol MR examinations for preoperative evaluation in a single large-volume liver transplantation (LT) center. Three blinded abdominal radiologists reviewed the CT and MR images for vascular and biliary variations. The strength of agreement between CT and MR angiography was assessed using the kappa index. The detection rate of biliary anatomical variations was calculated. The sensitivity and specificity for detecting significant steatosis (>5%) were calculated. The estimated total volume and right lobe volumes measured by MR volumetry were compared with the corresponding CT volumetry measurements using the intraclass correlation coefficient (ICC). Among the 35 patients, 26 underwent LT. The measurement of agreement showed a moderate to substantial agreement between CT and MR angiography interpretations (kappa values, 0.47-0.79; p < 0.001). Combining T2-weighted and T1-weighted MR cholangiography techniques detected all biliary anatomical variations in 9 of the 26 patients. MR-proton density fat fraction showed a sensitivity of 100% (3/3) and a specificity of 91.3% (21/23) for detecting pathologically determined steatosis (>5%). MR volumetry reached an excellent agreement with CT volumetry (reviewers 1 and 2: ICC, 0.92; 95% CI, 0.84-0.96). Our one-stop comprehensive liver donor MR imaging protocol can provide complete information regarding hepatic vascular and biliary anatomies, hepatic parenchymal quality, and liver volume for living liver donor candidates and can replace composite multimodality evaluation.


Assuntos
Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Fígado/diagnóstico por imagem , Fígado/cirurgia , Fígado/irrigação sanguínea , Doadores Vivos
20.
Korean J Radiol ; 24(1): 39-50, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36606619

RESUMO

OBJECTIVE: To assess the contrast-enhanced CT and ultrasonography (US) findings of intracholecystic papillary neoplasm (ICPN) and determine the imaging features predicting ICPN associated with invasive carcinoma (ICPN-IC). MATERIALS AND METHODS: In this retrospective study, we enrolled 119 consecutive patients, including 60 male and 59 female, with a mean age ± standard deviation of 63.3 ± 12.1 years, who had pathologically confirmed ICPN (low-grade dysplasia [DP] = 34, high-grade DP = 35, IC = 50) and underwent preoperative CT or US. Two radiologists independently assessed the CT and US findings, focusing on wall and polypoid lesion characteristics. The likelihood of ICPN-IC was graded on a 5-point scale. Univariable and multivariable logistic regression analyses were performed to identify significant predictors of ICPN-IC separately for wall and polypoid lesion findings. The performances of CT and US in distinguishing ICPN-IC from ICPN with DP (ICPN-DP) was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: For wall characteristics, the maximum wall thickness (adjusted odds ratio [aOR] = 1.4; 95% confidence interval [CI]: 1.1-1.9) and mucosal discontinuity (aOR = 5.6; 95% CI: 1.3-23.4) on CT were independently associated with ICPN-IC. Among 119 ICPNs, 110 (92.4%) showed polypoid lesions. Regarding polypoid lesion findings, multiplicity (aOR = 4.0; 95% CI: 1.6-10.4), lesion base wall thickening (aOR = 6.0; 95% CI: 2.3-15.8) on CT, and polyp size (aOR = 1.1; 95% CI: 1.0-1.2) on US were independently associated with ICPN-IC. CT showed a higher diagnostic performance than US in predicting ICPN-IC (AUC = 0.793 vs. 0.676; p = 0.002). CONCLUSION: ICPN showed polypoid lesions and/or wall thickening on CT or US. A thick wall, multiplicity, presence of wall thickening in the polypoid lesion base, and large polyp size are imaging findings independently associated with invasive cancer and may be useful for differentiating ICPN-IC from ICPN-DP.


Assuntos
Carcinoma , Neoplasias da Vesícula Biliar , Humanos , Masculino , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Estudos Retrospectivos , Ultrassonografia , Tomografia Computadorizada por Raios X/métodos
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