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1.
J Magn Reson Imaging ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946400

RESUMO

Schizophrenia is a severe mental illness that significantly impacts the lives of affected individuals and with increasing mortality rates. Early detection and intervention are crucial for improving outcomes but the lack of validated biomarkers poses great challenges in such efforts. The use of magnetic resonance imaging (MRI) in schizophrenia enables the investigation of the disorder's etiological and neuropathological substrates in vivo. After decades of research, promising findings of MRI have been shown to aid in screening high-risk individuals and predicting illness onset, and predicting symptoms and treatment outcomes of schizophrenia. The integration of machine learning and deep learning techniques makes it possible to develop intelligent diagnostic and prognostic tools with extracted or selected imaging features. In this review, we aimed to provide an overview of current progress and prospects in establishing clinical utility of MRI in schizophrenia. We first provided an overview of MRI findings of brain abnormalities that might underpin the symptoms or treatment response process in schizophrenia patients. Then, we summarized the ongoing efforts in the computer-aided utility of MRI in schizophrenia and discussed the gap between MRI research findings and real-world applications. Finally, promising pathways to promote clinical translation were provided. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

2.
J Org Chem ; 89(11): 8076-8083, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38767586

RESUMO

Patumantanes A-D (1-4), four new seco-polycyclic polyprenylated acylphloroglucinols (PPAPs) were isolated from Hypericum patulum. Patumantane A (1) was an unprecedented 1,2-seco-homoadamantane-type PPAP bearing a new 3,7-dioxatetracyclo[7.7.0.01,6.111,15]heptadecane architecture based on a 6/7/5/6 ring system. Patumantane B (2) was a unique 1,9-seco-adamantane-type PPAP with a tricyclo[4.4.4.0.02,12]tridecane core formed by a 6/6/6 carbon skeleton, and the further breakage between C-5 and C-9 decorated patumantane C (3) with the 9-nor-adamantane skeleton. More importantly, compounds 2 and 3 exhibited moderate immunosuppressive activity on Con A-induced T-lymphocyte proliferation in vitro, with IC50 values of 5.6 ± 1.2 and 11.2 ± 1.2 µM, respectively.


Assuntos
Hypericum , Floroglucinol , Hypericum/química , Floroglucinol/química , Floroglucinol/farmacologia , Floroglucinol/análogos & derivados , Floroglucinol/isolamento & purificação , Humanos , Estrutura Molecular , Carbono/química , Proliferação de Células/efeitos dos fármacos
3.
Bioorg Chem ; 144: 107145, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38278050

RESUMO

Hyperadamans A-G (1-7), seven new adamantane type polycyclic polyprenylated acylphloroglucinols (PPAPs), were isolated from Hypericum wilsonii N. Robson. Structurally, 1-4 were the first adamantanes bearing an unusual 2,7-dioxabicyclo-[2.2.1]-heptane fragment, and compound 5 was the first adamantane with a rare 1,6-dioxaspiro[4.4]nonane section. Importantly, 1-7 exhibited significant immunosuppressive activity on Con A-induced T-lymphocyte proliferation in vitro, with IC50 values ranging from 3.97 ± 0.10 to 18.12 ± 1.07 µM. Pretreatment with 1 in Con A-challenged autoimmune hepatitis mice could dramatically ameliorate the levels of hepatic injury indexes (ALT and AST) and reduce the product of proinflammatory cytokines (COX-2, IL-6, IL-1ß, IL-18, IL-23A and TNF-α). Furthermore, the protective effect of 1 on the Con A-induced liver injury was corroborated by the histological analysis and the immunohistochemistry.


Assuntos
Adamantano , Hepatite Autoimune , Camundongos , Animais , Concanavalina A , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/prevenção & controle , Adamantano/farmacologia , Adamantano/química , Citocinas , Fator de Necrose Tumoral alfa , Estrutura Molecular
4.
Cereb Cortex ; 33(10): 5957-5967, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-36513368

RESUMO

Alterations of radiomic features (RFs) in gray matter are observed in schizophrenia, of which the results may be limited by small study samples and confounding effects of drug therapies. We tested for RFs alterations of gray matter in never-treated first-episode schizophrenia (NT-FES) patients and examined their associations with known gene expression profiles. RFs were examined in the first sample with 197 NT-FES and 178 healthy controls (HCs) and validated in the second independent sample (90 NT-FES and 74 HCs). One-year follow-up data were available from 87 patients to determine whether RFs were associated with treatment outcomes. Associations between identified RFs in NT-FES and gene expression profiles were evaluated. NT-FES exhibited alterations of 30 RFs, with the greatest involvement of microstructural heterogeneity followed by measures of brain region shape. The identified RFs were mainly located in the central executive network, frontal-temporal network, and limbic system. Two baseline RFs with the involvement of microstructural heterogeneity predicted treatment response with moderate accuracy (78% for the first sample, 70% for the second sample). Exploratory analyses indicated that RF alterations were spatially related to the expression of schizophrenia risk genes. In summary, the present findings link brain abnormalities in schizophrenia with molecular features and treatment response.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Esquizofrenia/complicações , Substância Cinzenta/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Córtex Cerebral , Encéfalo
5.
Cerebrovasc Dis ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37989121

RESUMO

Background The hyperdense lesion on non-contrast CT (NCCT) is a common postoperative phenomenon in acute ischemic stroke (AIS) patients who are treated with endovascular therapy (EVT). Both contrast extravasation and hemorrhagic transformation presented hyperdense lesions on NCCT, which are sometimes difficult to distinguish them. Summary of Review Radiographic findings are important for identifying contrast extravasation and hemorrhagic transformation. We recommended a standardized follow-up protocol involving imaging and clinical evaluation as it will allow neurologists and neuroradiologists to reveal the relationships between these hyperdensities and various clinical outcomes. Key Messages Dual-energy CT and susceptibility weighted imaging are capable of distinguishing contrast extravasation and hemorrhagic transformation at an early stage after EVT. However, in institutions without access to such technology, a follow-up protocol based on NCCT is crucial.

6.
Bioorg Chem ; 135: 106530, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37054517

RESUMO

Hepatic ischemia/reperfusion injury is a major cause of hypohepatia after surgical procedures such as hypovolemic shock, transplantation, and so on. In our continuous study of bioactive natural products from fungus, eight ergosterol-type sterides (1-8), including two undescribed compounds, sterolaspers A (1) and B (2), were isolated from Aspergillus sp. TJ507. Structure elucidation was accomplished by extensive spectroscopic analysis and comparison with the reported NMR data as well as X-Ray single crystal diffraction tests. Activity screen of these isolates showed 5α-stigmast-3,6-dione (3) possessing anti-hypoxia injury effects against CoCl2-induced hypoxia damage in hepatocytes. More importantly, compound 3 could improve liver function, alleviate liver damage, and restrain the hepatocellular apoptosis in hepatic ischemia/reperfusion injury murine model. As such, this ergosterol-type steride, 5α-stigmast-3,6-dione (3), might serve as lead structure for the development of novel hepatoprotective agents in the clinical treatment of hepatic ischemia/reperfusion injury.


Assuntos
Fígado , Traumatismo por Reperfusão , Camundongos , Animais , Hepatócitos , Traumatismo por Reperfusão/tratamento farmacológico , Apoptose , Isquemia/complicações , Aspergillus
7.
Cell Mol Biol Lett ; 28(1): 71, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658291

RESUMO

Mechanical pressure overload and other stimuli often contribute to heart hypertrophy, a significant factor in the induction of heart failure. The UDP-glucose ceramide glycosyltransferase (UGCG) enzyme plays a crucial role in the metabolism of sphingolipids through the production of glucosylceramide. However, its role in heart hypertrophy remains unknown. In this study, UGCG was induced in response to pressure overload in vivo and phenylephrine stimulation in vitro. Additionally, UGCG downregulation ameliorated cardiomyocyte hypertrophy, improved cardiomyocyte mitochondrial oxidative stress, and reduced the ERK signaling pathway. Conversely, UGCG overexpression in cardiomyocytes promoted heart hypertrophy development, aggravated mitochondrial oxidative stress, and stimulated ERK signaling. Furthermore, the interaction between beta-1,4-galactosyltransferase 5 (B4GalT5), which catalyses the synthesis of lactosylceramide, and UGCG was identified, which also functions as a synergistic molecule of UGCG. Notably, limiting the expression of B4GalT5 impaired the capacity of UGCG to promote myocardial hypertrophy, suggesting that B4GalT5 acts as an intermediary for UGCG. Overall, this study highlights the potential of UGCG as a modulator of heart hypertrophy, rendering it a potential target for combating heart hypertrophy.


Assuntos
Ceramidas , Glicosiltransferases , Humanos , Transdução de Sinais , Cardiomegalia , Estresse Oxidativo
8.
Artigo em Inglês | MEDLINE | ID: mdl-37971438

RESUMO

Background: Lumbar disc herniation (LDH) remains one of the extremely common diseases in the elderly population, and despite the fact that percutaneous transforaminal endoscopic discectomy (PTED) can be an effective treatment for LDH, prognostic recurrence of the patients is still a clinical problem that needs to be addressed. Objective: To perform a meta-analysis of the influencing factors of disease recurrence after PTED for LDH to provide evidence for clinical practice. Methods: By screening the PubMed, EMbase, and Cochrane Library databases for relevant studies on disease recurrence after PTED for LDH, we extracted the authors, publication time, outcome measures, and other indicators were extracted for meta-analyses using RevMan 5.3 software. Results: The online retrieval and rigorous screening returned 8 valid articles for analysis, all with high reference value, as their Newcastle Ottawa Scale (NOS) scores were above 6. According to meta-analyses, there were no differences in gender and LDH type and location among patients with LDH recurrence after PTED treatment (P > .05); however, statistical significance was present in Pfirrmann grading, incomplete nucleus pulposus removal during surgery, and Modic changes (P < .05), indicating that these indexes were the influencing factors of LDH recurrence. Conclusions: Pfirrmann grading, incomplete nucleus pulposus removal during surgery, and Modic changes are related factors affecting LDH recurrence after PTED.

9.
Ecotoxicol Environ Saf ; 249: 114390, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508787

RESUMO

Florpyrauxifen-benzyl is an herbicide that has been developed in recent years. Its degradation mode in paddy soil environments is not clear. In this study, the degradation dynamics in paddy soil and water were studied by ultrahigh-performance liquid chromatography. Microbial degradation was the main degradation pathway. Using third-generation high-throughput sequencing technology, the changes in the soil bacterial community structure were studied. After 30 days of application, compared with the control group (F0), the abundance of Sphingomonas, Lysobacter, and Flavisolibacter in the recommended and repeated application groups (F1, F5 and F10) increased significantly, and uncultured bacterium and Terrimonas decreased significantly. Compared with the F0 and F1 groups, the species diversity of the F0 and F1 groups showed a significant increase over time. The species diversity of the F5 and F10 groups decreased significantly on Days 5 and 15. On Day 30, the recovery even exceeded that of the control group. Luteimonas and five other genera were positively correlated with herbicide residues, and Pseudolabrys and two other genera were negatively correlated. Repeated application showed a significant effect on the structure of the soil bacterial community, mainly showing a trend of a significant decrease in the initial stage and gradual recovery in the later stage. The results will guide the safe and rational use of florpyrauxifen-benzyl and provide a scientific basis for florpyrauxifen-benzyl dynamic supervision of environmental pollution and protection of black soil in Northeast China.


Assuntos
Herbicidas , Oryza , Solo , Microbiologia do Solo , Bactérias/genética , China , Bacteroidetes , Herbicidas/toxicidade
10.
Zhongguo Zhong Yao Za Zhi ; 48(8): 2203-2211, 2023 Apr.
Artigo em Zh | MEDLINE | ID: mdl-37282908

RESUMO

This study aims to investigate the therapeutic effect of alcohol extract of root and root bark of Toddalia asiatica(TAAE) on collagen-induced arthritis(CIA) in rats through phosphatidylinoinosidine-3 kinase/protein kinase B(PI3K/Akt) signaling pathway. To be specific, CIA was induced in rats, and then the rats were treated(oral, daily) with TAAE and Tripterygium Glycoside Tablets(TGT), respectively. The swelling degree of the hind leg joints was scored weekly. After 35 days of administration, the histopathological changes were observed based on hematoxylin and eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the levels of cytokines [tumor necrosis factor-α(TNF-α), interleukin(IL)-6)]. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining was performed to detect the apoptosis of synoviocytes in rats. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma 2(Bcl-2)-associated X(Bax), Bcl-2, and caspase-3 and pathway-related proteins phosphoinositide 3-kinase(PI3K), phosphorylated(p)-PI3K, protein kinase B(Akt), and p-Akt. RT-qPCR was conducted to examine the mRNA levels of Bax, Bcl-2, caspase-3, TNF-α, IL-6, and IL-1ß and pathway-related proteins PI3K, p-PI3K, Akt, and p-Akt. TAAE can alleviate the joint swelling in CIA rats, reduce serum levels of inflammatory cytokines, improve synovial histopathological changes, promote apoptosis of synoviocytes, and inhibit synovial inflammation. In addition, RT-qPCR and Western blot results showed that TAAE up-regulated the level of Bax, down-regulated the level of Bcl-2, and activated caspase-3 to promote apoptosis in synoviocytes. TAAE effectively down-regulated the protein levels of p-PI3K and p-Akt. In this study, TAAE shows therapeutic effect on CIA in rats and reduces the inflammation. The mechanism is that it suppresses PI3K/Akt signaling pathway and promotes synoviocyte apoptosis. Overall, this study provides a new clue for the research on the anti-inflammatory mechanism of TAAE and lays a theoretical basis for the better clinical application of TAAE in the treatment of inflammatory and autoimmune diseases.


Assuntos
Artrite Experimental , Extratos Vegetais , Zanthoxylum , Animais , Ratos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/induzido quimicamente , Citocinas/genética , Citocinas/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Casca de Planta/química , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Raízes de Plantas/química , Zanthoxylum/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sinoviócitos/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos
11.
Opt Express ; 30(8): 13148-13158, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35472936

RESUMO

White-light non-diffraction beams such as Airy beam and Bessel beam have potential applications in multispectral imaging and micromanipulation. Generation of white-light Airy beam and Bessel beam with high quality and high efficiency still remains challenging for conventional diffractive or refractive optics which suffers from significant chromatic dispersion. In this paper, both high-quality white-light Airy beam and Bessel beam are generated using a deformable mirror by modulating the incident LED beam with tunable cubic and conical wavefronts. The main lobe of the generated white-light non-diffraction beams does not suffer from chromatic dispersion along the propagation. The results also show that the generation of the white-light Bessel beam has higher requirements for spatial coherence than white-light Airy beams. Our work expands the understanding of the white-light non-diffraction beams and paves the way for the applications.

12.
Circ Res ; 127(4): e108-e125, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32392088

RESUMO

RATIONALE: Doxorubicin is one of the most potent antitumor agents available; however, its clinical use is restricted because it poses a risk of severe cardiotoxicity. Previous work has established that CircITCH (circular RNA ITCH [E3 ubiquitin-protein ligase]) is a broad-spectrum tumor-suppressive circular RNA and that its host gene, ITCH (E3 ubiquitin protein ligase), is involved in doxorubicin-induced cardiotoxicity (DOXIC). Whether CircITCH plays a role in DOXIC remains unknown. OBJECTIVE: We aimed to dissect the role of CircITCH in DOXIC and further decipher its potential mechanisms. METHODS AND RESULTS: Circular RNA sequencing was performed to screen the potentially involved circRNAs in DOXI pathogenesis. Quantitative polymerase chain reaction and RNA in situ hybridization revealed that CircITCH was downregulated in doxorubicin-treated human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as well as in the autopsy specimens from cancer patients who suffered from doxorubicin-induced cardiomyopathy. Cell death/viability assays, detection of cardiomyocyte necrosis markers, microelectrode array, and cardiomyocyte functional assays revealed that CircITCH ameliorated doxorubicin-induced cardiomyocyte injury and dysfunction. Detection of cellular/mitochondrial oxidative stress and DNA damage markers verified that CircITCH alleviated cellular/mitochondrial oxidative stress and DNA damage induced by doxorubicin. RNA pull-down assays, Ago2 immunoprecipitation and double fluorescent in situ hybridization identified miR-330-5p as a direct target of CircITCH. Moreover, CircITCH was found to function by acting as an endogenous sponge that sequestered miR-330-5p. Bioinformatic analysis, luciferase reporter assays, and quantitative polymerase chain reaction showed that SIRT6 (sirtuin 6), BIRC5 (baculoviral IAP repeat containing 5, Survivin), and ATP2A2 (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2, SERCA2a [SR Ca2+-ATPase 2]) were direct targets of miR-330-5p and that they were regulated by the CircITCH/miR-330-5p axis in DOXIC. Further experiments demonstrated that CircITCH-mediated alleviation of DOXIC was dependent on the interactions between miR-330-5p and the 3'-UTRs of SIRT6, BIRC5, and ATP2A2 mRNA. Finally, AAV9 (adeno-associated virus serotype 9) vector-based overexpression of the well-conserved CircITCH partly prevented DOXIC in mice. CONCLUSIONS: CircITCH represents a novel therapeutic target for DOXIC because it acts as a natural sponge of miR-330-5p, thereby upregulating SIRT6, Survivin and SERCA2a to alleviate doxorubicin-induced cardiomyocyte injury and dysfunction.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/efeitos adversos , MicroRNAs/metabolismo , RNA Circular/fisiologia , Proteínas Repressoras/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Sirtuínas/metabolismo , Survivina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Regiões 3' não Traduzidas/genética , Adenovírus Humanos , Animais , Proteínas Argonautas/análise , Sítios de Ligação , Biomarcadores , Cardiotoxicidade/genética , Cardiotoxicidade/metabolismo , Cardiotoxicidade/terapia , Morte Celular , Sobrevivência Celular , Dano ao DNA , Regulação para Baixo , Inativação Gênica , Genes Supressores de Tumor , Humanos , Imunoprecipitação/métodos , Hibridização in Situ Fluorescente/métodos , Camundongos , MicroRNAs/genética , Mitocôndrias Cardíacas/metabolismo , Mutação , Contração Miocárdica/fisiologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Necrose , Estresse Oxidativo , RNA Circular/efeitos dos fármacos , Proteínas Repressoras/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Survivina/genética , Ubiquitina-Proteína Ligases/genética , Regulação para Cima
13.
Org Biomol Chem ; 20(6): 1284-1291, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35072672

RESUMO

Spihyperglucinols A (1) and B (2), the first 13,15-nor-polycyclic polyprenylated acylphloroglucinols (PPAPs) featuring a 7/6/5 tricyclic ring system based on an unexpected bicyclo[3.2.2]nonane core, along with three new congeners, spihyperglucinols C-E (3-5), were isolated from Hypericum longistylum. Importantly, 1 and 2 displayed potential inhibitory effects on the production of nitric oxide in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with IC50 values of (8.70 ± 1.18) and (9.23 ± 1.26) µM, respectively, comparable to the positive control, dexamethasone, with an IC50 value of (9.76 ± 1.13) µM.


Assuntos
Floroglucinol
14.
Pestic Biochem Physiol ; 182: 105031, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35249652

RESUMO

Glyphosate is a broad-spectrum and nonselective organophosphorus herbicide that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), an enzyme in the shikimate pathway in plants. A glyphosate-resistant fungus identified as Fusarium verticillioides was screened from soil subjected to long-term glyphosate application, and this fungus could grow in inorganic salt medium containing 90 mmol/L glyphosate. The optimum culture conditions identified via the response surface curve method were 28 °C and pH 7.0. The target gene epsps was cloned in this study, and the open reading frame contained 1170 nucleotides and putatively encoded 389 amino acid residues. Phylogenetic analysis showed that this gene belonged to class I, genes naturally sensitive to glyphosate. q-PCR confirmed that the relative expression level of the epsps gene was low, and no significant difference in expression was observed among different glyphosate concentrations at 12 h or 48 h. On day 28, the degradation by Fusarium verticillioides C-2 of sterilized soil and unsterilized soil supplemented with 60 mg/kg glyphosate reached 72.17% and 89.07%, respectively, and a significant difference was observed between the treatments with and without the glyphosate-degrading strain. The recovery of soil dehydrogenase activity after the addition of Fusarium verticillioides was significantly higher than that in the absence of the degrading fungus on the 28th day. The results showed that C-2 is a highly effective glyphosate-degrading strain with bioremediation potential for glyphosate-contaminated soil.


Assuntos
3-Fosfoshikimato 1-Carboxiviniltransferase , Herbicidas , 3-Fosfoshikimato 1-Carboxiviniltransferase/genética , Biodegradação Ambiental , Fusarium , Glicina/análogos & derivados , Resistência a Herbicidas/genética , Herbicidas/farmacologia , Filogenia , Glifosato
15.
J Biol Chem ; 295(52): 18179-18188, 2020 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-33097593

RESUMO

Bone morphogenetic protein-9 (BMP-9) is a circulating cytokine that is known to play an essential role in the endothelial homeostasis and the binding of BMP-9 to the receptor activin-like kinase 1 (ALK-1) promotes endothelial cell quiescence. Previously, using an unbiased screen, we identified ALK-1 as a high-capacity receptor for low-density lipoprotein (LDL) in endothelial cells that mediates its transcytosis in a nondegradative manner. Here we examine the crosstalk between BMP-9 and LDL and how it influences their interactions with ALK-1. Treatment of endothelial cells with BMP-9 triggers the extensive endocytosis of ALK-1, and it is mediated by caveolin-1 (CAV-1) and dynamin-2 (DNM2) but not clathrin heavy chain. Knockdown of CAV-1 reduces BMP-9-mediated internalization of ALK-1, BMP-9-dependent signaling and gene expression. Similarly, treatment of endothelial cells with LDL reduces BMP-9-induced SMAD1/5 phosphorylation and gene expression and silencing of CAV-1 and DNM2 diminishes LDL-mediated ALK-1 internalization. Interestingly, BMP-9-mediated ALK-1 internalization strongly re-duces LDL transcytosis to levels seen with ALK-1 deficiency. Thus, BMP-9 levels can control cell surface levels of ALK-1, via CAV-1, to regulate both BMP-9 signaling and LDL transcytosis.


Assuntos
Receptores de Activinas Tipo II/metabolismo , Caveolina 1/metabolismo , Membrana Celular/metabolismo , Endocitose , Endotélio Vascular/fisiologia , Fator 2 de Diferenciação de Crescimento/metabolismo , Lipoproteínas LDL/metabolismo , Receptores de Activinas Tipo II/genética , Caveolina 1/genética , Células Cultivadas , Endotélio Vascular/citologia , Fator 2 de Diferenciação de Crescimento/genética , Humanos , Fosforilação , Transdução de Sinais
16.
J Cell Biochem ; 122(2): 209-221, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32890431

RESUMO

Myocardial infarction (MI) will inevitably result in cardiac fibrosis. In this study, we investigated the effect of microRNA-145 (miR-145) and transcription factor sex-determining region Y box 9 (SOX9) in the production of cardiac fibrosis induced by MI. MI rat models were established by left anterior descending coronary artery (LAD) occlusion. Four weeks after LAD, the cardiac fibrosis level was assessed by Masson's trichrome staining. Cardiac fibroblasts (CFs) exposed to hypoxia were used to simulate MI-induced fibrosis. Flow cytometry, cell counting kit-8, and transwell assays were used to examine changes in CF apoptosis, proliferation, and migration, respectively. miR-145 expression was measured by quantitative real-time polymerase chain reaction. Immunofluorescence and Western blot analysis were performed to determine the relative expression of proteins. In comparison to the sham-operated group, the expression of miR-145 was significantly downregulated in the infarction peripheral area, whereas, SOX9 was upregulated. In the infarcted heart, the overexpression of miR-145 significantly ameliorated cardiac fibrosis and cardiac function, and there was a negative correlation between miR-145 and SOX9 expressions in hypoxic CFs in vitro. In addition, SOX9 was verified to be a functional target of miR-145. Overexpression of miR-145 or inhibition of SOX9 decreased CF proliferation, migration, and fibrosis, but augmented their apoptotic rate. Moreover, the upregulation of miR-145 or suppression of SOX9 inhibited AKT and ß-catenin signaling in hypoxic CFs. Taken together, this study highlights a potential treatment for cardiac fibrosis through the targeted regulation of SOX9 by miR-145, and our findings indicate that miR-145 exerts anti-fibrotic effects in MI via the negative regulation of SOX9 and its downstream AKT/GSK-3ß/ß-catenin pathways.


Assuntos
Fibroblastos/metabolismo , Fibrose/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição SOX9/metabolismo , beta Catenina/metabolismo , Animais , Fibrose/genética , Citometria de Fluxo , Glicogênio Sintase Quinase 3 beta/genética , Masculino , MicroRNAs/genética , Infarto do Miocárdio/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição SOX9/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , beta Catenina/genética
17.
Angiogenesis ; 24(3): 631-645, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33650028

RESUMO

OBJECTIVE: The glucocorticoid receptor (GR) is a member of the nuclear receptor family that controls key biological processes in the cardiovascular system and has recently been shown to modulate Wnt signaling in endothelial cells. Wnt/ß-catenin signaling has been demonstrated to be crucial in the process of angiogenesis. In the current study, we studied whether GR could regulate angiogenesis via the Wnt/ß-catenin pathway. APPROACH AND RESULTSA: Key components of the Wnt/ß-catenin pathway were evaluated using quantitative PCR and Western blot in the presence or absence of GR. Enhanced angiogenesis was found in GR deficiency in vitro and confirmed with cell viability assays, proliferation assays and tube formation assays. Consistent with these in vitro findings, endothelial cell-specific GR loss GR in vivo promoted angiogenesis in both a hind limb ischemia model and sponge implantation assay. Results were further verified in a novel mouse model lacking endothelial LRP5/6, a key receptor in canonical Wnt signaling, and showed substantially suppressed angiogenesis using these same in vitro and in vivo assays. To further investigate the mechanism of GR regulation of Wnt signaling, autophagy flux was investigated in endothelial cells by visualizing auto phagolysosomes as well as by assessing P62 degradation and LC3B conversion. Results indicated that potentiated autophagy flux participated in GR-Wnt regulation. CONCLUSIONS: Lack of endothelial GR triggers autophagy flux, leads to activation of Wnt/ß-catenin signaling and promotes angiogenesis. There may also be a synergistic interaction between autophagy and Wnt/ß-catenin signaling.


Assuntos
Neovascularização Fisiológica , Receptores de Glucocorticoides/deficiência , Regulação para Cima , Via de Sinalização Wnt , beta Catenina/metabolismo , Animais , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos , Camundongos Knockout , Receptores de Glucocorticoides/metabolismo , beta Catenina/genética
18.
BMC Psychiatry ; 21(1): 538, 2021 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-34715831

RESUMO

BACKGROUND: The corpus callosum (CC) deficits have been well documented in chronic schizophrenia. However, the long-term impacts of antipsychotic monotherapies on callosal anatomy remain unclear. This cross-sectional study sought to explore micro- and macro-structural characteristics of the CC in never-treated patients and those with long-term mono-antipsychotic treatment. METHODS: The study included 23 clozapine-treated schizophrenia patients (CT-SCZ), 19 risperidone-treated schizophrenia patients (RT-SCZ), 23 never-treated schizophrenia patients (NT-SCZ), and 35 healthy controls (HCs). High resolution structural images and diffusion tensor imaging (DTI) data for each participant were obtained via a 3.0 T MR scanner. FreeSurfer was used to examine the volumes and fractional anisotropy (FA) values of the CC for each participant. RESULTS: There were significant deficits in the total and sub-regional CC volume and white matter integrity in NT-SCZ in comparison with healthy subjects. Compared with NT-SCZ, both CT-SCZ and RT-SCZ showed significantly increased FA values in the anterior CC region, while only RT-SCZ showed significantly increased volume in the mid-anterior CC region. Moreover, the volume of the mid-anterior CC region was significantly smaller in CT-SCZ compared to HCs. No correlations of clinical symptoms with callosal metrics were observed in schizophrenia patients. CONCLUSIONS: Our findings provide insight into micro- and macro-structural characteristics of the CC in chronic schizophrenia patients with or without antipsychotics. These results suggest that the pathology itself is responsible for cerebral abnormalities in schizophrenia and that chronic exposure to antipsychotics may have an impact on white matter structure of schizophrenia patients, especially in those with risperidone treatment.


Assuntos
Clozapina , Esquizofrenia , Anisotropia , Clozapina/uso terapêutico , Corpo Caloso/diagnóstico por imagem , Estudos Transversais , Imagem de Tensor de Difusão , Humanos , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
19.
J Craniofac Surg ; 32(2): e167-e171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33705062

RESUMO

ABSTRACT: The calcifying epithelial odontogenic tumor (CEOT) is a rare benign odontogenic tumor, which usually presents with distension of affected tissues. Radiologically, the lesions are often associated with an unerupted tooth and may have spot calcification shadows. The authors report a case of a CEOT in a 48-year-old male involving the right mandibular jaw bone and mentum soft tissues. The authors performed hemimandibulectomy and enucleation followed by reconstruction of the mandible using a vascularized free fibular flap through a digital surgical technique in order to restore the patient's facial symmetry and prepare the area for functional restorations. The case illustrates who the free fibular flap graft can be used for satisfactory mandibular reconstruction and restoration of the morphology and functions.


Assuntos
Retalhos de Tecido Biológico , Neoplasias Mandibulares , Reconstrução Mandibular , Tumores Odontogênicos , Neoplasias Cutâneas , Fíbula/cirurgia , Humanos , Masculino , Neoplasias Mandibulares/diagnóstico por imagem , Neoplasias Mandibulares/cirurgia , Pessoa de Meia-Idade , Tumores Odontogênicos/diagnóstico por imagem , Tumores Odontogênicos/cirurgia
20.
Sensors (Basel) ; 21(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34502791

RESUMO

The similar analysis of time sequence images to achieve image matching is a foundation of tasks in dynamic environments, such as multi-object tracking and dynamic gesture recognition. Therefore, we propose a matching method of time sequence images based on the Siamese network. Inspired by comparative learning, two different comparative parts are designed and embedded in the network. The first part makes a comparison between the input image pairs to generate the correlation matrix. The second part compares the correlation matrix, which is the output of the first comparison part, with a template, in order to calculate the similarity. The improved loss function is used to constrain the image matching and similarity calculation. After experimental verification, we found that it not only performs better, but also has some ability to estimate the camera pose.

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