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1.
Materials (Basel) ; 17(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38673129

RESUMO

This work has studied the co-addition of Sc and Zr elements into the Al-1.75wt%Fe-1.25wt%Ni eutectic alloy. The changes in the microstructure, electrical conductivity, and Vickers hardness of the Al-1.75wt%Fe-1.25wt%Ni-0.2wt%Sc-0.2wt%Zr alloy during heat treatment were studied. The results showed that two-step aging can effectively improve the aging response of the alloy over the single-step aging method. This was ascribed to the minimization of the diffusion difference between Sc and Zr elements. Furthermore, the homogenization treatment can also improve the aging response of the alloy by alleviating the uneven distribution of Sc and Zr. Nevertheless, the micro-alloyed elements exceeded the solid solubility limit in the Al-1.75wt%Fe-1.25wt%Ni-0.2wt%Sc-0.2wt%Zr alloy, and their strengthening effect has ever achieved the best prospect. Finally, both Sc and Zr contents were reduced simultaneously, and the aging response of the Al-1.75wt%Fe-1.25wt%Ni-0.15wt%Sc-0.1wt%Zr alloy was improved by optimized heat treatment. The underlying mechanisms for this alloy design and the corresponding microstructure-mechanical property relationship were analytically discussed.

3.
Biosci Trends ; 17(5): 369-380, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37813644

RESUMO

The elderly comprises over one-third of hepatocellular carcinoma (HCC) patients, however, they are not adequately represented in prognostic studies. The study aims to determine the prognostic significance of the preoperative prognostic nutritional index (PNI) and develop nomograms for predicting their recurrence-free and overall survival (RFS and OS). The study consisted of 282 elderly patients (aged ≥ 65 years) with early-stage HCC (China Liver Cancer Staging System: I-IIA) after curative resection (R0). They were randomly divided into a training (n = 197) and a test cohort (n = 85). The patients were stratified into two groups: PNI-low (PNI ≤ 49.05) and PNI-high (PNI > 49.05) based on a cut-off value. Most patients' demographics and perioperative outcomes were comparable, while patients in the PNI-high group were younger (P = 0.002), heavier (P < 0.001), and had lower comorbidity rates (P = 0.003). Although the tumor stages were earlier in the PNI-low group (P < 0.001), patients' OS (5-year OS: 48.9% vs. 93.1%) and RFS (5-year RFS: 27.3% vs. 75.7%) were significantly worse compared to the PNI-high group (both P < 0.0001). Patients' OS and RFS nomograms were developed by incorporating independent survival predictors including chronic obstructive pulmonary disease (COPD), age ≥ 75 years, PNI-low, tumor presence of satellite nodules, capsule, and microvascular invasion. The nomograms showed good calibration and discrimination, with all C-indexes ≥ 0.75 and calibration plots essentially coinciding with the diagonal. In conclusion, for elderly HCC patients, COPD, age ≥ 75 years, PNI-low, and tumor presence of satellite nodules, capsule, and microvascular invasion were independent prognostic factors. The nomogram could accurately predict the prognosis of these patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Doença Pulmonar Obstrutiva Crônica , Idoso , Humanos , Carcinoma Hepatocelular/cirurgia , Avaliação Nutricional , Prognóstico , Neoplasias Hepáticas/cirurgia
4.
J Mater Chem B ; 11(39): 9443-9458, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37727116

RESUMO

In this study, a 3D porous poly(ε-caprolactone)/polyethylene glycol (PCL/PEG) composite artificial tubular bile duct was fabricated for extrahepatic bile duct regeneration. PCL/PEG composite scaffolds were fabricated by 3D printing, and the molecular structure, mechanical properties, thermal properties, morphology, and in vitro biocompatibility were characterized for further application as artificial bile ducts. A bile duct defect model was established in beagle dogs for in vivo implantation. The results demonstrated that the implanted PE1 ABD, serving as a supportive scaffold, effectively stimulated the regeneration of a new bile duct comprising CK19-positive and CK7-positive epithelial cells within 30 days. Remarkably, after 8 months, the newly formed bile duct exhibited an epithelial layer resembling the normal structure. Furthermore, the study revealed collagen deposition, biliary muscular formation, and the involvement of microvessels and fibroblasts in the regenerative process. In contrast, the anastomotic area without ABD implantation displayed only partial restoration of the epithelial layer, accompanied by fibroblast proliferation and subsequent bile duct fibrosis. These findings underscore the limited inherent repair capacity of the bile duct and underscore the beneficial role of the PE1 ABD artificial tubular bile duct in promoting biliary regeneration.

5.
Expert Rev Gastroenterol Hepatol ; 17(9): 937-947, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37531090

RESUMO

BACKGROUND: Common bile duct stones (CBDS) have a reported recurrence rate of 4%-24% after stone extraction. The most commonly applied stone extraction method is endoscopic cholangiopancreatography (ERCP). We conducted a systematic review and meta-analysis to identify all available risk factors for recurrent CBDS following stone retraction. RESEARCH DESIGN AND METHODS: A literature search of studies with case-control design was performed to identify potential risk factors for recurrent CBDS. The impact of different risk factors on stone recurrence was analyzed. Pooled odds ratios (ORs) with 95% CIs and heterogeneity were calculated. Identified risk factors were graded as 'strong,' 'moderate,' or 'weak' after quality assessment. RESULTS: A total of 46 studies discussing stone recurrence following ERCP treatment were included. CBD diameter≥1.5 cm, sharp CBD angulation, multiple ERCP sessions, postoperative pneumobilia, history of CBD incision, and biliary stent placement were identified as strong risk factors; larger CBD diameter, periampullary diverticulum, mechanical lithotripsy, and history of cholecystectomy were identified as moderate. Other weak risk factors were also listed. CONCLUSIONS: In this comprehensive study, we identified 14 risk/protective factors for recurrent CBDS following ERCP. Pooled odds ratios were calculated and evaluated the quality of evidence. These findings may shed light on the assessment and management of CBDS.


Assuntos
Coledocolitíase , Cálculos Biliares , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Esfinterotomia Endoscópica/efeitos adversos , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/cirurgia , Fatores de Risco , Ducto Colédoco/cirurgia , Coledocolitíase/etiologia , Coledocolitíase/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
6.
Signal Transduct Target Ther ; 8(1): 283, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37468460

RESUMO

Adjuvants are indispensable components of vaccines. Despite being widely used in vaccines, their action mechanisms are not yet clear. With a greater understanding of the mechanisms by which the innate immune response controls the antigen-specific response, the adjuvants' action mechanisms are beginning to be elucidated. Adjuvants can be categorized as immunostimulants and delivery systems. Immunostimulants are danger signal molecules that lead to the maturation and activation of antigen-presenting cells (APCs) by targeting Toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) to promote the production of antigen signals and co-stimulatory signals, which in turn enhance the adaptive immune responses. On the other hand, delivery systems are carrier materials that facilitate antigen presentation by prolonging the bioavailability of the loaded antigens, as well as targeting antigens to lymph nodes or APCs. The adjuvants' action mechanisms are systematically summarized at the beginning of this review. This is followed by an introduction of the mechanisms, properties, and progress of classical vaccine adjuvants. Furthermore, since some of the adjuvants under investigation exhibit greater immune activation potency than classical adjuvants, which could compensate for the deficiencies of classical adjuvants, a summary of the adjuvant platforms under investigation is subsequently presented. Notably, we highlight the different action mechanisms and immunological properties of these adjuvant platforms, which will provide a wide range of options for the rational design of different vaccines. On this basis, this review points out the development prospects of vaccine adjuvants and the problems that should be paid attention to in the future.


Assuntos
Adjuvantes de Vacinas , Vacinas , Adjuvantes Imunológicos/química , Imunidade Inata , Receptores Toll-Like
8.
Front Plant Sci ; 14: 1164078, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37223791

RESUMO

Introduction: Conductance-photosynthesis (Gs-A) models, accompanying with light use efficiency (LUE) models for calculating carbon assimilation, are widely used for estimating canopy stomatal conductance (Gs) and transpiration (Tc) under the two-leaf (TL) scheme. However, the key parameters of photosynthetic rate sensitivity (gsu and gsh) and maximum LUE (ϵmsu and ϵmsh) are typically set to temporally constant values for sunlit and shaded leaves, respectively. This may result in Tc estimation errors, as it contradicts field observations. Methods: In this study, the measured flux data from three temperate deciduous broadleaved forests (DBF) FLUXNET sites were adopted, and the key parameters of LUE and Ball-Berry models for sunlit and shaded leaves were calibrated within the entire growing season and each season, respectively. Then, the estimations of gross primary production (GPP) and Tc were compared between the two schemes of parameterization: (1) entire growing season-based fixed parameters (EGS) and (2) season-specific dynamic parameters (SEA). Results: Our results show a cyclical variability of ϵmsu across the sites, with the highest value during the summer and the lowest during the spring. A similar pattern was found for gsu and gsh, which showed a decrease in summer and a slight increase in both spring and autumn. Furthermore, the SEA model (i.e., the dynamic parameterization) better simulated GPP, with a reduction in root mean square error (RMSE) of about 8.0 ± 1.1% and an improvement in correlation coefficient (r) of 3.7 ± 1.5%, relative to the EGS model. Meanwhile, the SEA scheme reduced Tc simulation errors in terms of RMSE by 3.7 ± 4.4%. Discussion: These findings provide a greater understanding of the seasonality of plant functional traits, and help to improve simulations of seasonal carbon and water fluxes in temperate forests.

9.
Intractable Rare Dis Res ; 11(4): 161-172, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36457589

RESUMO

As a consequence of breakthroughs in the area of guidelines research, the therapy for cholangiocarcinoma has significantly improved the efficacy rate of diagnosis and survival outcomes. We compared the most recently updated clinical practice guidelines and consensus to provide recommendations based on the diagnostic and therapeutic equipment available in various countries. Following a systematic review, we discovered that these guidelines and consensus had both similarities and differences in terms of what organizations or groups drafted the guidelines and the approach, applicability, content and recent updates of the guidelines as well as in terms of diagnostic and treatment algorithms. The disparities could be attributable to a variety of etiological factors, high risk patients, health resources, medical technology, treatment options, and income levels. Additionally, while complete adoption of guidelines may benefit physicians, patients, and authorities, there remains a disconnect between expected goals and implementation.

10.
Biosci Trends ; 16(1): 20-30, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35197399

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer-related mortality worldwide. This review is an updated version that summarizes comprehensive guidelines published from January 2001 to January 2022 worldwide with a focus on the clinical management of HCC. The electronic databases MEDLINE, the Chinese SinoMed, and the Japanese CiNii were systematically searched. A total of 22 characteristic guidelines for HCC management were ultimately included, including 1 international guideline, 11 guidelines from Asia, 5 from Europe, 4 from the America, and 1 from Australia. If guidelines were published in multiple versions, the most recent update was included, and surveillance, diagnosis, and treatment were compared. The composition of and recommendations in current guidelines on HCC varied, so these guidelines were regrouped and diagnostic and treatment algorithms were summarized graphically to provide the latest information to clinicians. The diagnostic criteria were grouped into 2 categories: a "Size-based pathway" and a "Non-size-based pathway". The treatment criteria were summarized according to different treatment algorithms, and mainstream treatment options were reviewed. Findings from comparison of current guidelines might help target and concentrate efforts to improve the clinical management of HCC. However, further studies are needed to improve the management and outcomes of HCC. More straightforward or refined guidelines would help guide doctors to make better decisions in the treatment of HCC in the future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Algoritmos , Austrália , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia
11.
Cancer Manag Res ; 14: 37-47, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35018120

RESUMO

PURPOSE: The time-to-tumor recurrence can predict the prognosis of hepatobiliary cancers following curative-intent resection. Therefore, for patients with gallbladder carcinoma (GBC) of stage T1b-T3 who had undergone R0 resection, we investigated the risk factors for early recurrence of GBC and their prognosis. PATIENTS AND METHODS: A total of 260 patients with GBC with T1b-T3 disease and an R0 margin were identified. Their clinicopathologic characteristics, perioperative details and prognostic data were reviewed. Survival analyses were carried out using the Kaplan-Meier method. Logistic regression models were used to identify the risk factors for early recurrence. RESULTS: The optimal cutoff for early recurrence was 29 months. Early recurrence tended to result in relapse far from the primary tumor, and such patients tended to have significantly worse overall survival. Multivariate analysis revealed that T3 disease, N1/N2 stage, poor differentiation of tumor, and lymphovascular invasion (LI) were associated with a greater risk of early recurrence. Patients diagnosed as having GBC incidentally and who had the risk factors of early recurrence were more likely to benefit from re-resection 2-4 weeks after a cholecystectomy. CONCLUSION: T3 stage, N1-N2 stage, poor differentiation, and LI were independent risk factors associated with early recurrence for patients with GBC with stage T1b-T3 disease after R0 resection.

12.
Front Genet ; 12: 722208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659344

RESUMO

The lack of an accurate biomarker in hepatocellular carcinoma (HCC) has hindered early detection, diagnosis, and treatment. Circular RNAs (circRNAs), which can be used as novel biomarkers in liquid biopsies, have been brought to light as a result of the advances in research on molecular biomarkers and the progression of genomic medicine. We conducted a meta-analysis of the diagnostic accuracy of serum/plasma circRNAs or the combination of circRNAs and α-fetoprotein (AFP) in HCC. We identified eight studies that met the inclusion/exclusion criteria from PubMed, Web of Science, EMBASE, and Cochrane Library databases. The data were pooled, and the sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) with 95% confidence intervals (CIs) were calculated. The areas under the summary receiver operator characteristic (SROC) curves (AUCs) were also calculated. The sensitivity of circRNAs was 0.82 (95% CI: 0.78-0.85), and the specificity was 0.82 (95% CI: 0.78-0.86). The sensitivity of AFP was 0.65 (95% CI: 0.61-0.68), and the specificity was 0.90 (95% CI: 0.85-0.93). The AUC was 0.89 (95% CI: 0.86-0.91) for circRNAs and 0.77 (95% CI: 0.74-0.81) for AFP. The sensitivity of the combination of circRNAs and AFP was 0.88 (95% CI: 0.84-0.92), specificity was 0.86 (95% CI: 0.80-0.91), and AUC was 0.94 (95% CI: 0.91-0.96). Additionally, a subgroup analysis was conducted based on the control groups used; the diagnostic accuracy was particularly high in the comparison of HCC vs. healthy controls. In summary, serum/plasma circRNAs are accurate biomarkers suitable for clinical use for detecting HCC, and the combination of circRNAs and AFP improved the diagnostic accuracy.

13.
BMC Gastroenterol ; 21(1): 329, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433421

RESUMO

BACKGROUND: Mixed adenoneuroendocrine carcinoma is a rare clinical manifestation, especially in the gastric and ampullary. The purpose of this study was to investigate the clinicopathological features and prognosis of mixed adenoneuroendocrine carcinoma in the gastric and ampullary and summarize related treatment suggestions. METHODS: In all, 32 cases of mixed adenoneuroendocrine carcinoma in the gastric and ampullary that were diagnosed from resected specimens were analyzed from 2009 to 2015. The corresponding demographic, clinicopathological and survival data were retrospectively reviewed. RESULTS: The 1-year, 3-year and 5-year survival rates were 78.1%, 28.1 and 9.4%, respectively, and the median overall survival was 28.0 months. In all, 75.0% (24/32) had lymph node metastasis at the time of initial diagnosis. A multivariate analysis revealed that TNM stage (HR 6.444 95%CI 1.477-28.121 P = 0.013), lymph nodes metastasis (HR10.617 95%CI 1.409-79.997 P = 0.022), vascular invasion (HR 5.855 95%CI 1.719-19.940 P = 0.005), grade of the adenocarcinoma component (HR 3.876 95%CI 1.451-10.357 P = 0.007) and CD56 positivity (HR 0.265 95%CI 0.100-0.705 P = 0.008) were independent predictors of overall survival. CONCLUSIONS: Mixed adenoneuroendocrine carcinoma is an aggressive clinical entity with a poor prognosis. Taking both the neuroendocrine component and the adenocarcinoma component into consideration of optimal treatment is strongly recommended.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Ampola Hepatopancreática/cirurgia , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
14.
Am J Surg ; 221(3): 642-648, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32859350

RESUMO

BACKGROUND: The effect of postsurgical radiotherapy (PSRT) among T1-3 gallbladder cancer (GBC) patients with one to three lymph node metastases remains controversial. The aim of this study was to assess the impact of PSRT on gallbladder cancer-specific survival (GBCSS) in patients with stage IIIB. METHODS: The data of GBC patients were obtained from the American Surveillance, Epidemiology, and End Results (SEER) Data resources between 2004 and 2015. Then, a 1:1 propensity score matching (PSM) method was performed. GBCSS was compared among all patients. Subgroup analysis was conducted to identify patients who would benefit from PSRT. RESULTS: 726 AJCC (8th edition) stage IIIB GBC patients were included. PSRT failed to improve GBCSS (p = 0.168). Male sex, tumor size ≥ 4 cm and absence of chemotherapy were independent negative prognostic factors. No significant survival benefit from PSRT was found in any subgroup. CONCLUSIONS: PSRT provides no survival benefit for IIIB GBC.


Assuntos
Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Colecistectomia , Neoplasias da Vesícula Biliar/radioterapia , Neoplasias da Vesícula Biliar/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Feminino , Neoplasias da Vesícula Biliar/patologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Radioterapia Adjuvante , Programa de SEER , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
15.
Medicine (Baltimore) ; 99(33): e21801, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872081

RESUMO

Acute appendicitis (AA) is the most common nonobstetric surgical emergency during pregnancy. According to the current guidelines and meta-analyses, traditional open appendectomy (OA) is still recommended for pregnant patients over laparoscopic appendectomy (LA), which might be associated with higher rates of fetal loss. Previous studies and experiences indicated that LA might be safe in the second trimester of pregnancy. The current study aimed to evaluate the safety and feasibility of LA in pregnant women during the second trimester.At our institution, a retrospective study was conducted with pregnant patients who underwent LA or OA during the second trimester between January 2016 and August 2018.A total of 48 patients were enrolled. Of them, 12 were managed with laparoscopy and 36 with the open approach. We found that the LA group had higher BMIs than the OA group (4.0 ±â€Š4.3 vs 21.5 ±â€Š2.9, P = .031). The financial results showed that the average daily medical costs for patients who underwent LA was higher than those who underwent OA (444 ±â€Š107 US$ vs 340 ±â€Š115 US$, P = .009), while the total cost of hospitalization was comparable between the 2 approaches. The perioperative and obstetric outcomes were comparable between LA and OA. In each group, only 1 patient had fetal loss. No "Yinao" was found in any of the patients in the LA group.In this study, with the proven advantages of the laparoscopic techniques, LA was found to be safe and feasible for pregnant women during the second trimester.


Assuntos
Apendicectomia/estatística & dados numéricos , Apendicite/cirurgia , Laparoscopia/estatística & dados numéricos , Complicações na Gravidez/cirurgia , Adulto , Apendicectomia/métodos , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Estudos Retrospectivos , Adulto Jovem
16.
Int J Med Sci ; 17(12): 1704-1712, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714073

RESUMO

Background: Gallbladder cancer (GBC) is the most common malignancy of the biliary system. Early T stage GBC patients with distant metastasis are proven to have a worse prognosis. In this study, our aim was to construct and validate a novel nomogram for predicting distant metastasis in T1 and T2 GBC. Methods: Between 2004 and 2014, patients with T1 and T2 GBC were identified in the Surveillance, Epidemiology, and End Results (SEER) database. All of the eligible patients were randomly divided into training and validation cohorts. Univariate and multivariate analyses were used to assess significant predictive factors associated with distant metastasis. A nomogram was developed and validated by a calibration curve and receptor operating characteristic curve (ROC) analysis. Results: According to the inclusion and exclusion criteria, 3013 patients with historically confirmed AJCC stage T1 and T2 GBC were enrolled. Younger age, high pathological grade, nonadenocarcinoma, T1, N1 and larger tumor size correlated positively with the risk of distant metastasis. A novel nomogram was established to predict distant metastasis in early T stage GBC patients. Internal validation with a calibration plot in the training cohort showed that this nomogram was well calibrated. Through ROC curve analysis, the areas under the ROC curves in the training and validation cohorts were 0.723 and 0.679, respectively. Conclusions: Although some limitations exist in this predictive model, the nomogram revealed the relationship between the clinicopathological characteristics of T1 and T2 GBC patients and the risk of distant metastasis. The novel nomogram will assist in patient counseling and guide treatment decision making for T1 and T2 GBC patients.


Assuntos
Carcinoma in Situ/diagnóstico , Neoplasias da Vesícula Biliar/diagnóstico , Metástase Neoplásica/diagnóstico , Nomogramas , Idoso , Carcinoma in Situ/diagnóstico por imagem , Carcinoma in Situ/patologia , Feminino , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/patologia , Estadiamento de Neoplasias , Curva ROC , Medição de Risco , Fatores de Risco , Programa de SEER
17.
Mol Nutr Food Res ; 63(18): e1801407, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31298459

RESUMO

SCOPE: Alzheimer's disease (AD) is a detrimental neurodegenerative disease and has no known effective treatment. The essential nutrient choline potentially plays an important role in cognition. Perinatal choline supplementation (CS) is critical for memory performance. Findings have shown that postnatal choline-containing compounds enhance memory functions in populations with memory impairments. However, whether CS can be targeted to decelerate the progression of AD remains unknown. METHODS AND RESULTS: APP/PS1 mice and their wild-type littermates are fed either a control or CS diet from 2 to 11 months of age. As compared to WT mice, APP/PS1 mice on the control diet are characterized by the reduction in the number of cholinergic neurons in the basal forebrain, reduced cholinergic fiber staining intensity in the amygdala, and reduced hippocampal and cerebral cortical levels of choline and acetylcholine. CS partially prevents these changes and ameliorates cognitive deficits and anxiety. Furthermore, amyloid-ß deposition and microgliosis are decreased in the APP/PS1 mice fed a CS diet. These effects may have been due to inhibition of NLRP3 inflammasome activation and restoration of synapse membrane formation. CONCLUSION: These findings reveal a beneficial effect of CS on AD progression during adulthood and provide a likely therapeutic intervention for AD patients.


Assuntos
Doença de Alzheimer/dietoterapia , Colina/farmacologia , Peptídeos beta-Amiloides/metabolismo , Animais , Ansiedade/dietoterapia , Comportamento Animal/efeitos dos fármacos , Neurônios Colinérgicos/efeitos dos fármacos , Transtornos Cognitivos/dietoterapia , Suplementos Nutricionais , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Inflamassomos/efeitos dos fármacos , Masculino , Camundongos Mutantes , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Membranas Sinápticas/efeitos dos fármacos
18.
Biosci Trends ; 13(3): 234-244, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31178528

RESUMO

Mitochondrial trans-2-enoyl-CoA reductase (MECR) is a protein-coding gene, and the protein encoded by this gene is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis (mtFASII). Numerous studies have shown disorder of lipid metabolism is closely related with malignance, especially in liver cancer. Through pre-experiment, we found that the expression of MECR gene was highly expressed in hepatocelluar carcinoma (HCC) cell lines in vitro. This suggests that the MECR gene may play a role of oncogene in HCC. Therefore, we conducted a preliminary experimental study on the role of MECR gene in HCC cells in vitro. Objective to explore whether the MECR gene can affect the malignant biological behavior of HCC. We selected HCC cell line BEL-7404 as experimental cell, which involves the highest expression of MECR in the pre-experiment. We constructed MECR knockdwon lentivirus vector, and then infected HCC cell lines to down-regulate MECR expression, and establish negative control group (NC). Through various experiments of cytology, our study showed that knockdown of MECR inhibited cell proliferation and colony formation, promoted apoptosis, and inhibited metastasis in HCC cell lines BEL-7404. MECR might serve as a novel gene therapeutic target for the treatment of HCC. Further study is needed to elucidate the signaling pathway through which MECR functions in HCC.


Assuntos
Apoptose/fisiologia , Carcinoma Hepatocelular/metabolismo , Ciclo Celular/fisiologia , Neoplasias Hepáticas/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Apoptose/genética , Western Blotting , Carcinoma Hepatocelular/genética , Ciclo Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Neoplasias Hepáticas/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
19.
Stem Cell Res Ther ; 10(1): 153, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151403

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and communication and stereotypical patterns of behaviors, interests, or activities. Even with the increased prevalence of ASD, there is no defined standard drug treatment for ASD patients. Currently, stem cells, including human amniotic epithelial cell (hAEC) transplantation, seem to be a promising treatment for ASD, but the effectiveness needs to be verified, and the mechanism has not been clarified. METHODS: We intraventricularly transplanted hAECs into a 2-month-old BTBR T+tf/J (BTBR) mouse model of ASD. Behavior tests were detected 1 month later; hippocampal neurogenesis, neuroprogenitor cell (NPC) pool, and microglia activation were analyzed with immunohistochemistry and immunofluorescence; the levels of pro-inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were determined by real-time PCR or western blotting. RESULTS: After intraventricular injection of hAECs into adult males, social deficits in BTBR mice were significantly ameliorated. In addition, hAEC transplantation restored the decline of neurogenesis and NPCs in the hippocampus of BTBR mice by expanding the stem cell pool, and the decreased levels of BDNF and TrkB were also rescued in the hippocampus of the hAEC-injected BTBR mice. Meanwhile, the transplantation of hAECs did not induce microglial overactivation or excessive production of pro-inflammatory cytokines in the hippocampus of BTBR mice. CONCLUSIONS: Based on these results, we found that hAEC transplantation ameliorated social deficits and promoted hippocampal neurogenesis in BTBR mice. Our study indicates a promising therapeutic option that could be applied to ASD patients in the future.


Assuntos
Âmnio/transplante , Transtorno do Espectro Autista/terapia , Neurogênese/genética , Animais , Transplante de Células , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Transdução de Sinais
20.
Brain Res Bull ; 150: 75-85, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31047973

RESUMO

Autism spectrum disorder (ASD) is diagnosed by two core symptoms: impaired social communication and the presence of repetitive, stereotyped behaviors and/or restricted interests. Alterations in serotonergic signaling are involved in the genesis of ASD. Selective serotonin reuptake inhibitors (SSRIs) have been reported to reduce repetitive behaviors and rescue social deficits in ASD mouse models and patients. In the present study, we examined the potential of citalopram (a representative selective serotonin reuptake inhibitor) on sociability and repetitive behaviors in the BTBR T+Itpr3tf/J (BTBR) mouse model of ASD. We found that the deficits of sociability in the BTBR mice were reversed by a 20 mg/kg dose of citalopram treatment without any adverse effects on locomotor activity or anxiety level. In addition, both high (20 mg/kg) and low (10 mg/kg) doses decreased the repetitive behavior of marble burying but did not affect self-grooming behavior. Furthermore, both doses were shown to have antidepressant-like activity in both the B6 and the BTBR mice in the tail suspension test. Taken together, these findings further demonstrate that citalopram can alleviate behavioral abnormalities in the BTBR autism model and lend support to the hypothesis that SSRIs may be potential therapeutic drugs for the treatment of behavioral dysfunctions in ASD.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Citalopram/farmacologia , Animais , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Modelos Animais de Doenças , Asseio Animal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Distribuição Aleatória , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Comportamento Social , Comportamento Estereotipado/efeitos dos fármacos
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