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1.
Angew Chem Int Ed Engl ; 63(2): e202311165, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-37930784

RESUMO

A robust electrochemically driven nickel-catalyzed halogen exchange of unsaturated halides and triflates (Br to Cl, I to Cl, I to Br, and OTf to Cl) is reported. A combination of NiCl2 ⋅ glyme as the precatalyst, 2,2'-bipyridine as a ligand, NMP as the solvent, and electrochemistry allowed the generation of a nickel species that promotes reductive elimination of the desired product. This paired electrochemical halogenation is compatible with a range of unsaturated halides and triflates, including heterocycles, dihaloarenes, and alkenes with good functional-group tolerance. Joint experimental and theoretical mechanistic investigations highlighted three catalytic events: i) oxidative addition of the aryl halide to a Ni(0) species to deliver a Ni(II) intermediate; ii) halide metathesis at Ni(II); iii) electrochemical oxidation of Ni(II) to Ni(III) to enable the formation of the desired aryl halide upon reductive elimination. This methodology allows the replacement of heavy halogens (I or Br) or polar atoms (O) with the corresponding lighter and more lipophilic Cl group to block undesired reactivity or modify the properties of drug and agrochemical candidates.

2.
Chemistry ; 27(72): 18066-18073, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34779056

RESUMO

We have successfully isolated and characterized the zinc carbamate complex (phen)Zn(OAc)(OC(=O)NHPh) (1; phen=1,10-phenanthroline), formed as an intermediate during the Zn(OAc)2 /phen-catalyzed synthesis of organic carbamates from CO2 , amines, and the reusable reactant Si(OMe)4 . Density functional theory calculations revealed that the direct reaction of 1 with Si(OMe)4 proceeds via a five-coordinate silicon intermediate, forming organic carbamates. Based on these results, the catalytic system was improved by using Si(OMe)4 as the reaction solvent and additives like KOMe and KF, which promote the formation of the five-coordinated silicon species. This sustainable and effective method can be used to synthesize various N-aryl and N-alkyl carbamates, including industrially important polyurethane raw materials, starting from CO2 under atmospheric pressure.

3.
Proc Natl Acad Sci U S A ; 115(34): E8027-E8036, 2018 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-30087184

RESUMO

Activated T cells undergo metabolic reprogramming and effector-cell differentiation but the factors involved are unclear. Utilizing mice lacking DUSP6 (DUSP6-/-), we show that this phosphatase regulates T cell receptor (TCR) signaling to influence follicular helper T (TFH) cell differentiation and T cell metabolism. In vitro, DUSP6-/- CD4+ TFH cells produced elevated IL-21. In vivo, TFH cells were increased in DUSP6-/- mice and in transgenic OTII-DUSP6-/- mice at steady state. After immunization, DUSP6-/- and OTII-DUSP6-/- mice generated more TFH cells and produced more antigen-specific IgG2 than controls. Activated DUSP6-/- T cells showed enhanced JNK and p38 phosphorylation but impaired glycolysis. JNK or p38 inhibitors significantly reduced IL-21 production but did not restore glycolysis. TCR-stimulated DUSP6-/- T cells could not induce phosphofructokinase activity and relied on glucose-independent fueling of mitochondrial respiration. Upon CD28 costimulation, activated DUSP6-/- T cells did not undergo the metabolic commitment to glycolysis pathway to maintain viability. Unexpectedly, inhibition of fatty acid oxidation drastically lowered IL-21 production in DUSP6-/- TFH cells. Our findings suggest that DUSP6 connects TCR signaling to activation-induced metabolic commitment toward glycolysis and restrains TFH cell differentiation via inhibiting IL-21 production.


Assuntos
Diferenciação Celular/fisiologia , Fosfatase 6 de Especificidade Dupla , Glicólise/fisiologia , Receptores de Antígenos de Linfócitos T , Transdução de Sinais/fisiologia , Linfócitos T Auxiliares-Indutores , Animais , Formação de Anticorpos/fisiologia , Antígenos CD28/genética , Antígenos CD28/imunologia , Antígenos CD28/metabolismo , Fosfatase 6 de Especificidade Dupla/genética , Fosfatase 6 de Especificidade Dupla/imunologia , Fosfatase 6 de Especificidade Dupla/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Interleucinas/genética , Interleucinas/imunologia , Interleucinas/metabolismo , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/imunologia , MAP Quinase Quinase 4/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/imunologia , Mitocôndrias/metabolismo , Consumo de Oxigênio/fisiologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Gynecol Oncol ; 143(1): 60-67, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27498588

RESUMO

OBJECTIVES: Synchronous endometrial and ovarian carcinomas (SEOCs) present gynecologic oncologists with a challenging diagnostic puzzle: discriminating between double primary cancers and single primary cancer with metastasis. We aimed to determine the clonal relationship between simultaneously diagnosed endometrial and ovarian carcinomas. METHODS: Fourteen pairs of SEOCs of endometrioid type and two pairs of SEOCs with disparate histologic types (control for dual primary tumors) were subjected to massively parallel sequencing (MPS) and molecular inversion probe microarrays. RESULTS: Thirteen of the 14 pairs of SEOCs harbored somatic mutations shared by both uterine and ovarian lesions, indicative of clonality. High degree of chromosomal instability in the tumors from 10 patients who received adjuvant chemotherapy, of whom 9 had synchronous carcinomas with significantly overlapping copy number alterations (CNAs), suggestive of single primary tumors with metastasis. The clonal relationship determined by genomic analyses did not agree with clinicopathological criteria in 11 of 14 cases. Minimal CNAs were identified in both ovarian and endometrial carcinomas in 4 patients, who did not receive adjuvant chemotherapy and experienced no recurrent diseases. In contrast, two of the 10 patients with chromosomally unstable cancers developed recurrent tumors. CONCLUSION: Our findings support a recent paradigm-shifting concept that most SEOCs originate from a single tumor. It also casts doubt on the clinicopathological criteria used to distinguish between dual primary tumors and single primary tumor with metastasis. Testing of CNAs on SEOCs may help determining the need of adjuvant therapy.


Assuntos
Carcinoma Endometrioide/genética , Variações do Número de Cópias de DNA , Neoplasias do Endométrio/genética , Neoplasias Primárias Múltiplas/genética , Neoplasias Ovarianas/genética , Adulto , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Primárias Múltiplas/patologia , Neoplasias Ovarianas/patologia
5.
Eur J Neurosci ; 42(7): 2455-66, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26201245

RESUMO

Neurexins are cell adhesion molecules that are important for synaptic plasticity and homeostasis, although links to sleep have not yet been investigated. We examined the effects of neurexin-1 perturbation on sleep in Drosophila, showing that neurexin-1 nulls displayed fragmented sleep and altered circadian rhythm. Conversely, the over-expression of neurexin-1 could increase and consolidate night-time sleep. This was not solely due to developmental effects as it could be induced acutely in adulthood, and was coupled with evidence of synaptic growth. The timing of over-expression could differentially impact sleep patterns, with specific night-time effects. These results show that neurexin-1 was dynamically involved in synaptic plasticity and sleep in Drosophila. Neurexin-1 and a number of its binding partners have been repeatedly associated with mental health disorders, including autism spectrum disorders, schizophrenia and Tourette syndrome, all of which are also linked to altered sleep patterns. How and when plasticity-related proteins such as neurexin-1 function during sleep can provide vital information on the interaction between synaptic homeostasis and sleep, paving the way for more informed treatments of human disorders.


Assuntos
Moléculas de Adesão Celular Neuronais/fisiologia , Ritmo Circadiano/fisiologia , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Plasticidade Neuronal/fisiologia , Sono/fisiologia , Animais , Comportamento Animal/fisiologia , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas de Drosophila/metabolismo
6.
iScience ; 27(7): 110388, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39092178

RESUMO

Phosphatase and tensin homolog (PTEN) is vital for B cell development, acting as a key negative regulator in the PI3K signaling pathway. We used CD23-cre to generate PTEN-conditional knockout mice (CD23-cKO) to examine the impact of PTEN mutation on peripheral B cells. Unlike mb1-cre-mediated PTEN deletion in early B cells, CD23-cKO mutants exhibited systemic inflammation with increased IL-6 production in mature B cells upon CpG stimulation. Inflammatory B cells in CD23-cKO mice showed elevated phosphatidylinositol 3-phosphate [PI(3)P] levels and increased TLR9 endosomal localization. Pharmacological inhibition of PI(3)P synthesis markedly reduced TLR9-mediated IL-6. Single-cell RNA-sequencing (RNA-seq) revealed altered endocytosis, BANK1, and NF-κB1 expression in PTEN-deficient B cells. Ectopic B cell receptor (BCR) expression on non-inflammatory mb1-cKO B cells restored BANK1 and NF-κB1 expression, enhancing TLR9-mediated IL-6 production. Our study highlights PTEN as a crucial inflammatory checkpoint, regulating TLR9/IL-6 axis by fine-tuning PI(3)P homeostasis. Additionally, BCR downregulation prevents the differentiation of inflammatory B cells in PTEN deficiency.

7.
Cell Rep Med ; : 101789, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39423810

RESUMO

Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery. Uncoupling GAT-1-Synt1A reverses stroke-induced GAT-1 dysfunction and cortical excitability decline and enhances synaptic GABAergic inhibition and consequently cortical oscillations and network plasticity by facilitating the assembly of the SNARE complex at the synapse. Based on the molecular mechanism of GAT-1 binding to Synt1A, we design GAT-1-Synt1A blockers. Among them, ZLQ-3 exhibits the greatest potency. Intranasal use of ZLQ-3-1, a glycosylation product of ZLQ-3, substantially lessens impairments of sensorimotor and cognitive functions in rodent models. This compound, or its analogs, may serve as a promoting agent for stroke recovery.

8.
Int Orthod ; 21(2): 100753, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37060684

RESUMO

PURPOSE: The objective of this study was to evaluate the mechanical, physical, and aesthetic properties of GUMMETAL® (GM) orthodontic archwires after the application of various aesthetic coating materials. METHODS: This in vitro study included 180 orthodontic wires: five experimental groups used 0.016×0.022-inch GM as the core-based wire followed by the application of epoxy, polytetrafluoroethylene (PTFE), clear ceramic, white ceramic, or silicone; and four control groups: 0.016×0.022-inch GM, 0.019×0.025-inch GM, 0.016×0.022-inch stainless steel (SS), and 0.019×0.025-inch SS. Frictional forces, force deflection rate, yield strength, aesthetic colour value, corrosive and wear resistance were compared between the experimental and control groups. RESULTS: Among the coated wires, white ceramic exhibited the highest frictional force (2.06±0.20 N) and silicone showed the lowest values (0.88±0.12 N). There were significant differences in static friction between experimental and control groups (P<0.001). PTFE coating had the highest force deflection rate (9.03±0.12 N/mm) and yield strength (10.0±0.14 N/mm) among coated wires and white ceramic exhibited the lowest values (6.86±0.14 N/mm and 7.74±0.17 N/mm for force deflection rate and yield strength, respectively). Differences in force deflection rate and yield strength between experimental and control groups were statistically significant (P<0.001). All coated wire groups had a clinical difference in colour when compared to A1 shade. Coated and uncoated wires showed good corrosion resistance after one week in corrosive saliva with no detectable loss of mass. CONCLUSIONS: This study has shown that coating wires can improve some aspects of the wire properties but not all when compared to uncoated GM and SS. Future investigation of the materials used in this study is required to further characterize their properties.


Assuntos
Cáusticos , Braquetes Ortodônticos , Humanos , Ligas Dentárias , Estética Dentária , Fios Ortodônticos , Fricção , Aço Inoxidável , Silicones , Politetrafluoretileno , Teste de Materiais , Titânio , Propriedades de Superfície
9.
Mil Med Res ; 10(1): 15, 2023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-36949519

RESUMO

BACKGROUND: Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. METHODS: This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. RESULTS: ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. CONCLUSIONS: ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.


Assuntos
Adesivos , Adesivos Teciduais , Ratos , Humanos , Suínos , Coelhos , Animais , Criogéis , Células CACO-2 , Inflamação
10.
Mitochondrial DNA B Resour ; 7(8): 1513-1515, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034530

RESUMO

Three mitochondrial genomes of the cetoniine beetle, Clinterocera nigra (Kano, 1931) were assembled via next-generation sequencing. The newly sequenced mitogenomes all have 37 genes, showing standard gene order and annotation as the other insects. To examine their phylogenetic positions and relationships between their elytral color (red-spot and melanistic forms) and sequence variation, a total of 118 public mitogenomes of Scarabaeidae were used to infer a maximum-likelihood (ML) tree. Our results show that the melanistic form is grouped within red-spot ones, revealing a population level variation on the elytra color. Our work also provides the first mitogenomic reference of myrmecophilous chafers.

11.
J Agric Food Chem ; 70(28): 8738-8745, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35795971

RESUMO

Luteolin (LUT), a plant-derived flavone, exhibits various bioactivities; however, the poor aqueous solubility hampers its applications. Here, we revealed bioconversion of LUT by Bacillus subtilis BCRC 80517, yielding three water-soluble phosphate conjugates. These derivatives were identified as luteolin 4'-O-phosphate (L4'P), luteolin 3'-O-phosphate (L3'P), and luteolin 7-O-phosphate (L7P) by LC-ESI-MS/MS and NMR. Besides, we found that Bacillus subtilis BCRC 80517 was able to convert different levels of LUT but showed a limited conversion rate. By observing bacterial morphology with transmission electron microscopy and confocal fluorescence microscopy, we found that LUT disrupted the bacterial membrane integrity, which explained the incomplete conversion. Additionally, we revealed a spontaneous intramolecular transesterification of L4'P to L3'P, the thermodynamically more stable form, under acidic conditions and proposed the possible mechanism involving a cyclic phosphate as the intermediate. This study provides insight into development of a potent structural modification strategy to enhance the solubility of LUT through biophosphorylation.


Assuntos
Bacillus subtilis , Luteolina , Cromatografia Líquida , Luteolina/química , Fosfatos , Espectrometria de Massas em Tandem
12.
J Plast Reconstr Aesthet Surg ; 75(7): 2359-2367, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35354546

RESUMO

BACKGROUND: The use of irradiated homologous costal cartilage (IHCC) as an alternative source of graft material for rhinoplasty remains controversial because of the risk of complications. Herein, we aimed to perform a comprehensive assessment of complications associated with IHCC use in rhinoplasty through a meta-analysis of published studies. METHODS: We searched the PubMed, Embase, and Cochrane Library databases to identify eligible published studies, and we evaluated the complication rates of IHCC use in rhinoplasty. Published studies meeting the inclusion criteria included clinical studies involving at least 10 patients and assessing at least 1 postoperative long-term complication of rhinoplasty. Two investigators independently extracted data from the included studies using a standardized form. Meta-analysis was performed using a random-effects model. The main outcomes were the rates of various complications, including the need for revision surgery. RESULTS: Ten studies involving a total of 959 patients were analyzed. The complication rates were 2.07% (95% confidence interval [CI], 0.80%-5.23%) for warping, 1.77% (95% CI, 1.10%-2.83%) for infection, 1.34% (95% CI, 0.34%-5.16%) for resorption, 2.13% (95% CI, 0.86%-5.19%) for displacement, 2.99% (95% CI, 1.24%-7.03%) for revision, 0.16% (95% CI, 0.01%-3.25%) for extrusion, and 2.04% (95% CI, 1.02%-4.02%) for avulsion. All the included trials had moderate-to-high methodological quality except for small sample sizes and subjectively reporting of some complications. CONCLUSIONS: The overall long-term complication rates associated with IHCC use in rhinoplasty were low. Revision and displacement were the most common complications at the one-year follow-up; surgeons should pay special attention to the risk of these complications. IHCC can serve as a reliable material for rhinoplasty and achieve good patient satisfaction.


Assuntos
Cartilagem Costal , Rinoplastia , Cartilagem Costal/transplante , Humanos , Satisfação do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Reoperação/efeitos adversos , Estudos Retrospectivos , Rinoplastia/efeitos adversos
13.
Front Microbiol ; 13: 989351, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338065

RESUMO

Fires lead to dramatic shifts in ecosystems and have a large impact on the biota. Soil organisms, especially soil fauna, are often used as indicators of environmental change. At present, minimal attention has been paid to using soil fauna as an indicator of environmental change after a fire. Here, a field survey of burnt herbaceous vegetation in semi-arid areas was conducted to determine the response of soil arthropods to fire and their short-term recovery after fire. Overall, the abundance and biomass of soil arthropods was more sensitive to fire than the number of groups. The number of soil arthropod groups, especially the dominant groups (mites and springtails), was not significantly affected by wildfires. At the unburned site, soil arthropod abundance showed significant seasonal shifts that may be related to the vegetation properties, temperature, and precipitation caused by seasonal changes. In contrast, soil arthropods at the burnt sites showed a delayed recovery and had only reached 56%-82%, 17%-54%, and 91%-190% of the biomass in the unburnt forest at the 3, 6, and 9 months after the burning event. Our findings of soil arthropod abundance changes in the present study suggest that fire-induced changes in soil and vegetation properties (e.g., AN, LT, and VC) were crucial factors for the changes in soil arthropod abundance in this semi-arid grassland. We conclude that fire disturbance reduces the seasonal sensitivity of soil arthropods by altering their habitat. This study furthers our understanding of wildfire impact recovery by documenting the short-term temporal dynamics of soil arthropods.

14.
Front Immunol ; 13: 872047, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35585971

RESUMO

An effective COVID-19 vaccine against broad SARS-CoV-2 variants is still an unmet need. In the study, the vesicular stomatitis virus (VSV)-based vector was used to express the SARS-CoV-2 Spike protein to identify better vaccine designs. The replication-competent of the recombinant VSV-spike virus with C-terminal 19 amino acid truncation (SΔ19 Rep) was generated. A single dose of SΔ19 Rep intranasal vaccination is sufficient to induce protective immunity against SARS-CoV-2 infection in hamsters. All the clones isolated from the SΔ19 Rep virus contained R682G mutation located at the Furin cleavage site. An additional S813Y mutation close to the TMPRSS2 cleavage site was identified in some clones. The enzymatic processing of S protein was blocked by these mutations. The vaccination of the R682G-S813Y virus produced a high antibody response against S protein and a robust S protein-specific CD8+ T cell response. The vaccinated animals were protected from the lethal SARS-CoV-2 (delta variant) challenge. The S antigen with resistance to enzymatic processes by Furin and TMPRSS2 will provide better immunogenicity for vaccine design.


Assuntos
COVID-19 , Furina , SARS-CoV-2 , Serina Endopeptidases , Animais , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19 , Furina/genética , Furina/metabolismo , Humanos , Imunidade Celular , SARS-CoV-2/imunologia , Serina Endopeptidases/genética , Serina Endopeptidases/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
15.
Mitochondrial DNA B Resour ; 6(4): 1341-1343, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33898751

RESUMO

Museum specimens are collected for education, exhibition, and various multiple scientific purposes. However, millions of specimens remain in their collection boxes for years without being analyzed. Historical specimens have been known to contain low-quality DNA; hence, it is difficult to utilize their sequence information in phylogenetic studies. However, recent advances in high-throughput sequencing (HTS) make these collections amenable to phylogenomic studies. In this study, two historical specimens (Papilio xuthus Linnaeus, 1767, and Papilio thoas Linnaeus, 1771) were sampled and DNA extracted for HTS via the Miseq platform. Two complete mitogenomes were assembled, even though the DNA quality of those specimens was highly fragmented, below 250 bp in length. The 37 genes of 60 mitogenomes were aligned and used for inferring the phylogenetic relationships of Papilioninae. These two newly sequenced mitogenomes are correctly grouped in the genus Papilio, and this result indicates that historical specimens show great potential for phylogenetic studies with HTS technology.

16.
J Dig Dis ; 22(2): 62-71, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33369216

RESUMO

Gallbladder cancer (GBC) is the most common form of biliary tract malignancy with a dismal prognosis. A poor outcome in patients with GBC is related to the aggressive nature of the tumor, delayed diagnosis, and a lack of reliable biomarkers and effective treatment. Therefore, early diagnosis and accurate disease assessment are crucial to prolonging the patient survival. Identification of novel prognostic and diagnostic biomarkers may help improve the early diagnostic rate and develop specific targeted treatments for patients with GBC. We herein review the novel biomarkers that may be associated with the diagnosis and prognosis in GBC and their potential clinical significance in the management of GBC.


Assuntos
Neoplasias da Vesícula Biliar , Biomarcadores Tumorais , Humanos , Prognóstico , Resultado do Tratamento
17.
Bioengineered ; 12(1): 708-719, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33522352

RESUMO

Reportedly, long non-coding RNA (lncRNA) are crucial modulators in neurodegenerative diseases. Herein, we investigated the role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in Parkinson's disease (PD). In-vitro PD model was established based on SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+). NEAT1, microRNA (miR) -124-3p and phosphodiesterase 4B (PDE4B) expression levels were examined by qRT-PCR. CCK-8 assay and LDH release assay were adopted to delve into the cell viability and cytotoxicity, respectively. Besides, western blot was utilized to determine mTOR, p-mTOR and PDE4B expression levels. ELISA was executed to detect the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6). Dual-luciferase reporter assay and RIP assay were used to probe the relationship between miR-124-3p and NEAT1 or PDE4B. We demonstrated that, in SH-SY5Y cells treated with MPP+, NEAT1 and PDE4B expression levels were raised, while miR-124-3p expression was repressed; NEAT1 depletion or miR-124-3p overexpression increased the cell viability and suppressed cell injury. Besides, miR-124-3p was confirmed as the direct target of NEAT1, and its down-regulation counteracted the impact of NEAT1 depletion on SH-SY5Y cells. PDE4B was as the downstream target of miR-124-3p, and its overexpression weakens the impact of miR-124-3p on SH-SY5Y cells. Additionally, NEAT1 decoyed miR-124-3p to modulate PDE4B expression. Collectively, in MPP+-induced SH-SY5Y cells, NEAT1 depletion increases cell viability, represses cytotoxicity and reduces inflammatory response by regulating miR-124-3p and PDE4B expression levels, suggesting that NEAT1 may be a promising target for treating PD.


Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Doença de Parkinson/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , RNA Longo não Codificante/metabolismo , Regulação para Cima
18.
World J Gastroenterol ; 27(16): 1664-1690, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33967550

RESUMO

Originally proposed by John McCarthy in 1955, artificial intelligence (AI) has achieved a breakthrough and revolutionized the processing methods of clinical medicine with the increasing workloads of medical records and digital images. Doctors are paying attention to AI technologies for various diseases in the fields of gastroenterology and hepatology. This review will illustrate AI technology procedures for medical image analysis, including data processing, model establishment, and model validation. Furthermore, we will summarize AI applications in endoscopy, radiology, and pathology, such as detecting and evaluating lesions, facilitating treatment, and predicting treatment response and prognosis with excellent model performance. The current challenges for AI in clinical application include potential inherent bias in retrospective studies that requires larger samples for validation, ethics and legal concerns, and the incomprehensibility of the output results. Therefore, doctors and researchers should cooperate to address the current challenges and carry out further investigations to develop more accurate AI tools for improved clinical applications.


Assuntos
Gastroenterologia , Radiologia , Inteligência Artificial , Humanos , Prognóstico , Estudos Retrospectivos
19.
Eur J Nucl Med Mol Imaging ; 37(4): 728-35, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20069296

RESUMO

PURPOSE: The diagnostic and prognostic value of (18)F-FDG PET in cervical adenocarcinoma/adenosquamous carcinoma (AC/ASC) is unclear. The aim of this study was to assess the value of PET in the management of cervical AC/ASC. METHODS: Patients with resectable FIGO stage IB/IIB cervical AC/ASC receiving a preoperative MRI scan and a PET or PET/CT scan before radical surgery were eligible. Diagnostic efficacy was compared by receiver operating characteristic (ROC) analysis. Correlations between clinicopathological parameters and outcome and maximum standardized uptake values (SUVmax) of FDG uptake were evaluated. RESULTS: The study group comprised 83 patients (mean age 48.3 + or - 9.7 years) Five-year overall survival was 85.5%, with a median follow-up time of 38.6 months (range 2.8-87.2 months). Pelvic lymph node (PLN) and paraaortic lymph node (PALN) metastases were seen in 32.5% and 8.4% of patients, respectively. The difference in diagnostic efficacy in identifying metastatic PALN between PET and MRI was significant (PET versus MRI, area under the curve 0.832 versus 0.607, p=0.039). SUVmax in primary tumour was correlated with LN metastasis and deep stromal invasion. Overall survival was significantly related to FIGO stage, PLN metastasis, deep cervical stromal invasion, tumour size measured by MRI, and SUVmax of the primary cervical tumour. CONCLUSION: PET provided significantly better diagnostic efficacy than MRI in detecting PALN metastasis. Poor prognostic factors in cervical AC/ASC were SUVmax of the primary cervical tumour >5.3, stage IIB, deep cervical stromal invasion, tumour size measured by MRI > or = 40 mm, and PLN metastasis.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma Adenoescamoso/diagnóstico por imagem , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Neoplasias do Colo do Útero/diagnóstico por imagem , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Área Sob a Curva , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/secundário , Carcinoma Adenoescamoso/cirurgia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Estimativa de Kaplan-Meier , Metástase Linfática/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico por imagem , Prognóstico , Curva ROC , Radiografia , Cintilografia , Estudos Retrospectivos , Carga Tumoral , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/cirurgia
20.
Implant Dent ; 19(6): 487-97, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21119353

RESUMO

PURPOSE: The biological effect of fluoridated hydroxyapatite (FHA) graft materials has been attributed to their fluoride ion content; but, only few studies have been conducted to explore the osteoblastic cellular response to physicochemical characteristics of them. We hypothesized that the effect of varied sintered FHA composites on osteoblastic behavior would attribute certain specified physicochemical characteristics of apatites. MATERIALS: Sintered FHA composites were prepared by sintering method with varied gravity percentages of calcium fluoride and hydroxyapatite. Scanning electron microscopic, x-ray diffraction, and Fourier-transform infrared analysis were recorded. The human fetal-osteoblast (hFOB 1.19) cells were seeded on the apatites and tissue culture plates. Responses to the apatites were assessed in terms of osteopontin (OPN) and type I collagen, COL I, gene differentiation. RESULTS: We observed the calcined hydroxyapatite (OHAp), sintered F- OHAps, and hydroxy fluorapatites (OH-FAps) with different physicochemical characteristics. The x-ray diffraction analysis showed sintered apatites to be fluorapatites. Otherwise, Fourier-transform infrared spectral patterns could differentiate the sintered F-OHAps from OH-FAps by the existence of OH, OH···F, or OH···F···OH bands. With ≤ 1 wt% CaF2 added, sintered F-OHAp composites expressed both OH and OH···F bands. With >1 wt% CaF2 added, sintered OH-FAp composites expressed both OH···F and OH···F···OH bands. Sintered F-OHAp composites could enhance OPN and COL I gene expression after 6-day culture (P ≤ 0.05). Otherwise, sintered OH-FAp composites inhibited the expression. CONCLUSION: The results revealed that sintered F-OHAp composites with both OH and OH···F bands were bioactive bone graft materials.


Assuntos
Substitutos Ósseos/química , Colágeno Tipo I/biossíntese , Células-Tronco Fetais/metabolismo , Hidroxiapatitas/química , Osteoblastos/metabolismo , Osteopontina/biossíntese , Análise de Variância , Fluoreto de Cálcio/análise , Diferenciação Celular , Linhagem Celular , Colágeno Tipo I/genética , Cristalografia por Raios X , Células-Tronco Fetais/citologia , Regulação da Expressão Gênica no Desenvolvimento , Temperatura Alta , Humanos , Microscopia Eletrônica de Varredura , Osteoblastos/citologia , Osteopontina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectroscopia de Infravermelho com Transformada de Fourier , Estatísticas não Paramétricas
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