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1.
Artigo em Inglês | MEDLINE | ID: mdl-35511323

RESUMO

BACKGROUND: Patients at high cardiovascular risk are closely associated with an increased risk of atrial fibrillation (AF). Whether proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) can attenuate AF progression remains unknown. METHODS: To compare PCSK9 mAbs with placebo or ezetimibe to explore the effect of PCSK9 mAbs therapy on the end-point of incidence of AF, we searched PubMed, Embase, and ClinicalTrials.gov for articles. We used Mantel-Haenszel risk ratio (RR) with corresponding 95% CI for the categorical data, including the incidence of AF and predefined other outcomes of interest. RESULTS: We included 21 articles consisting of 26 randomized controlled trials with a total of 95,635 participants. Quantitative synthesis revealed that PCSK9 mAbs significantly reduce the incidence of AF events (RR 0.84; 95% CI 0.72-0.98; p = 0.03), whereas no obvious differences were seen between the PCSK9 mAbs group and the ezetimibe group (RR 0.90; 95% CI 0.29-2.76; p = 0.85). PCSK9 mAbs also markedly decreased the incidence of cerebrovascular events (RR 0.75; 95% CI 0.66-0.85; p < 0.0001) and new-onset hypertension (RR 0.92; 95% CI 0.87-0.97; p = 0.003), but not the risk of cardiovascular death (RR 0.95; 95% CI 0.85-1.07; p = 0.40) and new-onset diabetes mellitus (RR 1.01; 95% CI 0.95-1.08; p = 0.67). CONCLUSIONS: Overall, the PCSK9 mAbs therapy reduced AF and presented certain cardiovascular benefits in patients at high cardiovascular risk. Further big-scale and long follow-up duration randomized controlled trials that compare PCSK9 mAbs with ezetimibe are required to evaluate the effect of PCSK9 mAbs versus ezetimibe on AF.

2.
J Thorac Dis ; 14(4): 1172-1182, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35572876

RESUMO

Background: It is considered that circRNA can participate in regulating the occurrence and effects of ventricular arrhythmia (VA) through competing endogenous RNA (ceRNA) mechanism, regulating pre-mRNA and regulating parental gene expression. Therefore, we used animal modeling and high-throughput differential screening to screen out circRNA related to VA and study its possible mechanism of action on VA. Methods: The rat model of myocardial ischemia VA was established. High-throughput screening of the differentiated circRNA was conducted and verified by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot. Lv-circRNA01724 lentivirus was constructed using molecular biology. Primary isolation of the rat cardiomyocytes, hypoxia modeling, Lv-circRNA01724 transfection, mode of action verification, and dual luciferase detection of circRNA01724 and miR-323-5p was performed. Results: Through qRT-PCR verification of circRNA01724, circRNA02230, circRNA02088, miR-323-5p, miR-330-5p, and miR-324-3p expressions, circRNA01724 was selected as the research object. Detection by Western blot showed significantly lower Cx43, ZO-1, and α-catenin expressions in rat myocardial tissue in the model group compared with the control group at 1, 7, 14, and 28 days old. On identification of the isolated primary rat cardiomyocytes by immunofluorescence, the α-SMA characteristic protein expression indicated that the isolation was successful. Verification of rat cardiomyocytes transfected with Lv-circRNA01724 suggested overexpression in cells. The miR-323-5p was also highly expressed in the rat cardiomyocyte hypoxia model following Lv-circRNA01724 transfection. Detection by flow cytometry showed that modeling of the transfected Lv-circRNA01724 had a significant increased apoptotic rate. Detection by Western blot showed that modeling of the transfected Lv-circRNA01724 cells had significantly decreased Cx43, ZO-1, and α-catenin compared with the model group. Conclusions: High-throughput screening of circRNA01724 can promote the apoptosis of hypoxic cardiomyocytes, which is related to the rat model of myocardial ischemia VA and may be a potential target for the treatment of VA.

3.
Photochem Photobiol ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506756

RESUMO

Blue light is a crucial environmental cue for fungi. Hypocrellin A (HA) is a photoactive perylenequinone from Shiraia with strong antimicrobial and anticancer properties. In this study, effects of the illumination of blue-light-emitting diode (LED) at 470 nm on Shiraia sp. S8 were investigated. Blue light at 50-200 lx and 4-6 h day-1 could enhance HA content in the mycelia, but suppress it at 300-400 lx or with longer exposure (8-24 h day-1 ). The intermittent blue light (6 h day-1 ) at 200 lx not only enhanced the fungal conidiation but also stimulated HA production without any growth retardation. The generation of fungal reactive oxygen species was induced to upregulate HA biosynthetic gene expressions. When the culture was maintained under the intermittent blue light for 8 days, HA production reached 242.76 mg L-1 , 2.27-fold of the dark control. On the other hand, both the degradation of HA and downregulation of HA biosynthetic genes occurred under long exposure time (8-24 h day-1 ), leading to the suppression of HA production. These results provide a basis for understanding the regulation of blue light on the biosynthesis of fungal photoactivated perylenequinones, and the application of a novel light elicitation to Shiraia mycelium cultures for enhanced HA production.

4.
J Clin Nurs ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35362192

RESUMO

AIM AND OBJECTIVES: This study explored the effect of transdermal buprenorphine on quality of life and six symptoms in cancer patients with pain. BACKGROUND: Transdermal opioids offer advantages over traditional routes of administration. The impact of transdermal buprenorphine on quality of life for patients with cancer in Asian populations is unknown. DESIGN: This study employed a single-arm observational repeated measures design. Cancer patients with pain were evaluated prior to treatment (baseline). Over a 4-week treatment period, quality of life and symptoms were assessed at 2 and 4 weeks. This study adhered to the recommendations of STROBE guidelines. METHODS: This multi-site study was conducted in six hospitals located across northern, middle and southern Taiwan. Adult cancer patients whose pain was previously stable with opioid analgesics and, based on clinical judgement, were able to convert to transdermal buprenorphine treatment were invited to participate. Quality of life was measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). RESULTS: Generalised estimating equations showed participants who completed at least one follow-up measurement (N = 80) over 4-weeks had a significant improvement in overall quality of life. Functional status only improved for social functioning. However, symptom severity decreased significantly for nausea/vomiting, pain, insomnia and constipation. CONCLUSIONS: The study provides initial evidence supporting transdermal buprenorphine for providing beneficial effects of improving quality of life and reducing severity of symptoms in Asian patients with cancer. RELEVANCE TO CLINICAL PRACTICE: The findings of this study can inform the clinical practice that the use of transdermal buprenorphine in cancer patients with pain may also reduce the severity of other symptoms and improve overall quality of life. TRIAL REGISTRATION DETAILS: This study was registered in ClinicalTrials.gov. Identifier: NCT04315831.

5.
Bioengineering (Basel) ; 9(4)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35447690

RESUMO

In this work, gold nanoparticles (AuNPs) and curcumin drug were incorporated in polyvinylidene fluoride (PVDF) nanofibers by electrospinning as a novel tissue engineering scaffold in nerve regeneration. The influence of AuNPs on the morphology, crystallinity, and drug release behavior of nanofiber membranes was characterized. A successful composite nanofiber membrane sample was observed by scanning electron microscopy (SEM). The addition of AuNPs showed the improved as well as prolonged cumulative release of the drug. The results indicated that PVDF-AuNPs nanofiber membrane could potentially be applied for nerve regeneration.

6.
Front Chem ; 10: 856495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464207

RESUMO

Copper (II) containing coordination complexes have attracted much attention for chemodynamic therapy (CDT) against cancer cells. In this study, the bimetallic nanobooster [Gd2Cu(L)2(H2O)10]·6H2O was prepared by a solvothermal method based on tetrazole carboxylic acid ligand H4L [H4L = 3,3-di (1H-tetrazol-5-yl) pentanedioic acid]. It showed considerable cytotoxicity toward three kinds of human cancer cells (HeLa, HepG2, and HT29). The MTT assay showed that the IC50 (half-maximal inhibitory concentration) of the complex NPs on HeLa cells (4.9 µg/ml) is superior to that of HepG2 (11.1 µg/ml) and HT29 (5.5 µg/ml). This result showed that [Gd2Cu(L)2(H2O)10]·6H2O NPs can inhibit cell proliferation in vitro and may be potential candidates for chemodynamic therapy. In addition, the cytotoxicity was also confirmed by the trypan blue staining experiment. The results promise the great potential of Gd(III)-Cu(II) for CDT against cancer cells.

7.
Front Endocrinol (Lausanne) ; 13: 802992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370961

RESUMO

Background: A network meta-analysis of randomized controlled trials (RCTs) was conducted to explore the cardiovascular outcomes of all the kind and dosages of sodium-glucose cotransport-2 (SGLT2) inhibitors in type 2 diabetes mellitus (T2DM) patients. Method and Result: The Cochrane Library, PubMed, and Embase databases were systematically searched for studies to compare the therapeutic effects of different SGLT2 inhibitors in T2DM patients. The effect measurements estimate chosen were odds ratios (ORs) and their corresponding 95% confidence interval (CI). Forty-seven RCTs involving a total of 70574 participants were eligible for direct and indirect comparisons. In direct comparison, treatment with dapagliflozin 5mg showed significantly lower risk of all-cause mortality compared with treatment with dapagliflozin 2.5mg (OR 0.09, 95% CI 0.01-0.70). According to NMA, interestingly, empagliflozin 10mg/25mg, and canagliflozin 100mg was associated with significantly lower risks of all-cause mortality compared with placebo (OR of 0.70, 95% CI 0.58-0.85; 0.69, 95% CI 0.57-0.84; and 0.83, 95% CI 0.73-0.95, respectively). Compared with placebo, dapagliflozin 10mg, empagliflozin 10mg and 25mg displayed the lower risks for cardiovascular events (OR 0.78, 95% CI 0.44-1.00; OR 0.47, 95% CI 0.22-0.93; and 0.43, 95% CI 0.24-0.74, respectively) by direct comparison. Moreover, canagliflozin 100/300mg showed significantly higher risks of cardiovascular events compared with empagliflozin 10mg (OR of 4.83, 95% CI 1.14-20.46 and 5.31, 95% CI 1.26-22.34, respectively) and empagliflozin 25mg (4.23, 95% CI 1.13-15.83 and 4.65, 95% CI 1.25-17.27, respectively) according to NMA. There were non-significant differences among all interventions in volume depletion in traditional pairwise meta-analysis. While in NMA, canagliflozin 100/300mg were associated with significantly increased risks of volume depletion compared with placebo (OR of 1.47, 95% CI 1.08-1.99 and 2.19, 95% CI 1.66-2.90, respectively). Conclusion: In the limitations of the NMA, this study showed that empagliflozin might be better than other SGLT2 inhibitors with low risks of all-cause mortality and cardiovascular events in patients with T2DM suggesting the need for ad hoc RCTs.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/complicações , Humanos , Hipoglicemiantes/uso terapêutico , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
8.
Front Physiol ; 13: 822763, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250624

RESUMO

PURPOSE: To determine whether intravoxel incoherent motion (IVIM) parameters correlate with liver regeneration and function recovery after partial hepatectomy (PH) in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. METHODS: Sixty-two adult Sprague-Dawley rats were divided into the control group and the fibrosis group with CCl4 injection for 8 weeks. At the end of the 8th week, all rats received left lateral lobe liver resection. Within each group, IVIM imaging (n = 10/group) and histologic and biochemical analyses (n = 3/group/time point) were performed pre- and post-PH (on days 1, 2, 3, 5, 7, 14, and 21). Differences in liver IVIM parameters and correlation between IVIM parameters and Ki-67 indices, hepatocyte diameter, alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) values were analyzed. RESULTS: Post-PH, liver true diffusion coefficient (D) values decreased and pseudodiffusion coefficient (D*) and perfusion fraction (PF) values increased, then recovered to pre-PH levels gradually in both fibrosis and control rats. PF in fibrosis group were significantly higher than in controls from 3 to 21 days (P < 0.05). In fibrosis rats, both Ki-67 indices and hepatocyte diameters increased, and a strong correlation was found between PF and Ki-67 indices (r = -0.756; P = 0.03), D* and PF values and ALT, AST, and TBil values (r = -0.762 to -0.905; P < 0.05). In control rats, only hepatocyte diameters increased, and all IVIM parameters correlated well with hepatocyte diameters, ALT, AST and TBil values (r = 0.810 to -1.000; P < 0.05). CONCLUSION: The regeneration pattern in fibrotic liver tissue was different compared with control livers. IVIM parameters can monitor liver regeneration and functional recovery non-invasively after PH.

9.
J Med Chem ; 65(6): 5134-5148, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35255688

RESUMO

Twelve new complexes Cu(L1)2-Cu(L12)2 were designed and synthesized to improve their chemotherapeutic properties. They showed considerable antiproliferative activity against T24 cancer cells but lower cytotoxicity to human normal cells HL-7702 and WI-38. A mechanism study indicated that Cu(L4)2 and Cu(L10)2 were reduced to Fenton-like Cu+ by glutathione depletion, and the resulting Cu+ catalyzed the generation of highly toxic hydroxyl radicals from excess H2O2. Simultaneously, Cu(L4)2 and Cu(L10)2 could decrease the catalase activity to restrain H2O2 transfer to H2O for enhanced chemodynamic therapy (CDT). These induced mitochondrial dysfunctions and endoplasmic reticulum stress to induce T24 cell apoptosis. In addition, Cu(L4)2 and Cu(L10)2 inhibited autophagy flux to promote cell apoptosis. Cu(L4)2 and Cu(L10)2 demonstrated strong tumor inhibition ability in the T24 xenograft model. Moreover, Cu(L10)2 showed higher antitumor activity and a better safety profile than the CDT agent Cu1. Cu(L10)2 exhibited excellent pharmacokinetic properties. Collectively, Cu(L4)2 and Cu(L10)2 could be developed as potential CDT candidates for cancer treatment.


Assuntos
Antineoplásicos , Hidroxiquinolinas , Neoplasias , Quinolinas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Autofagia , Linhagem Celular Tumoral , Cobre , Glutationa , Humanos , Peróxido de Hidrogênio/farmacologia , Neoplasias/tratamento farmacológico , Bases de Schiff/farmacologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-35260337

RESUMO

BACKGROUND: Due to the high heterogeneity among hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE), the prognosis of patients varies significantly. The decision-making on the initiation and/or repetition of TACE under different liver functions is a matter of concern in clinical practice. Thus, we aimed to develop a prediction model for TACE candidates using risk stratification based on varied liver function. METHODS: A total of 222 unresectable HCC patients who underwent TACE as their only treatment were included in this study. Cox proportional hazards regression was performed to select the independent risk factors and establish a predictive model for the overall survival (OS). The model was validated in patients with different Child-Pugh class and compared to previous TACE scoring systems. RESULTS: The five independent risk factors, including alpha-fetoprotein (AFP) level, maximal tumor size, the increase of albumin-bilirubin (ALBI) grade score, tumor response, and the increase of aspartate aminotransferase (AST), were used to build a prognostic model (ASARA). In the training and validation cohorts, the OS of patients with ASARA score ≤ 2 was significantly higher than that of patients with ASARA score > 2 (P < 0.001, P = 0.006, respectively). The ASARA model and its modified version "AS(ARA)" can effectively distinguish the OS (P < 0.001, P = 0.004) between patients with Child-Pugh class A and B, and the C-index was 0.687 and 0.706, respectively. For repeated TACE, the ASARA model was superior to Assessment for Retreatment with TACE (ART) and ALBI grade, maximal tumor size, AFP, and tumor response (ASAR) among Child-Pugh class A patients. For the first TACE, the performance of AS(ARA) was better than that of modified hepatoma arterial-embolization prognostic (mHAP), mHAP3, and ASA(R) models among Child-Pugh class B patients. CONCLUSIONS: The ASARA scoring system is valuable in the decision-making of TACE repetition for HCC patients, especially Child-Pugh class A patients. The modified AS(ARA) can be used to screen the ideal candidate for TACE initiation in Child-Pugh class B patients with poor liver function.

11.
Heart Surg Forum ; 25(1): E132-E139, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35238298

RESUMO

BACKGROUND: The objective was to develop and validate an individualized nomogram to predict severe functional tricuspid regurgitation (S-FTR) after mitral valve replacement (MVR) via retrospective analysis of rheumatic heart disease (RHD) patients' pre-clinical characteristics. METHODS: Between 2001-2015, 442 MVR patients of RHD were examined. Transthoracic echocardiography detected S-FTR, and logistic regression model analyzed its independent predictors. R software established a nomogram prediction model, and Bootstrap determined its theoretical probability, which subsequently was compared with the actual patient probability to calculate the area under the curve (AUC) and calibration plots. Decision curve analysis (DCA) identified its clinical utility. RESULTS: Ninety-six patients developed S-FTR during the follow-up period. Both uni- and multivariate analyses found significant correlations between S-FTR occurrence with gender, age, atrial fibrillation (AF), pulmonary arterial hypertension (PH), left atrial diameter (LAD), and tricuspid regurgitation area (TRA). The individualized nomogram model had the AUC of 0.99 in internal verification. Calibration test indicated high agreement of predicted and actual S-FTR onset. DCA also showed that utilization of those six aforementioned factors was clinically useful. CONCLUSION: The nomogram for the patient characteristics of age, gender, AF, PH, LAD, and TRA found that they were highly predictive for future S-FTR onset within 5 years. This predictive ability therefore allows clinicians to optimize postoperative patient care and avoid unnecessary tricuspid valve surgeries.


Assuntos
Insuficiência da Valva Mitral , Insuficiência da Valva Tricúspide , Pré-Escolar , Átrios do Coração , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/cirurgia , Estudos Retrospectivos , Insuficiência da Valva Tricúspide/diagnóstico , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/cirurgia
12.
Oxid Med Cell Longev ; 2022: 8622388, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242280

RESUMO

Chronic inflammatory pain seriously affects patients' quality of life because of a paucity of effective clinical treatments caused, at least in part, by lack of full understanding of the underlying mechanisms. miRNAs are known to be involved in inflammatory pain via silencing or degrading of target mRNA in the cytoplasm. The present study provides a novel mechanism by which miRNA-22 positively regulates metal-regulatory transcription factor 1 (Mtf1) in the nuclei of neurons in the dorsal horn of the spinal cord. We found that miRNA-22 was significantly increased in the dorsal horn of mice with either inflammatory pain induced by plantar injection of complete Freund's adjuvant (CFA) or neuropathic pain induced by unilateral sciatic nerve chronic constrictive injury (CCI). Knocking down or blocking miRNA-22 alleviated CFA-induced mechanical allodynia and heat hyperalgesia, whereas overexpressing miRNA-22 produced pain-like behaviors. Mechanistically, the increased miRNA-22 binds directly to the Mtf1 promoter to recruit RNA polymerase II and elevate Mtf1 expression. The increased Mtf1 subsequently enhances spinal central sensitization, as evidenced by increased expression of p-ERK1/2, GFAP, and c-Fos in the dorsal horn. Our findings suggest that the miRNA-22-Mtf1 signaling axis in the dorsal horn plays a critical role in the induction and maintenance of inflammatory pain. This signaling pathway may be a promising therapeutic target in inflammatory pain.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Hiperalgesia/metabolismo , MicroRNAs/metabolismo , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Células do Corno Posterior/metabolismo , Nervo Isquiático/lesões , Transdução de Sinais/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/genética , Animais , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Adjuvante de Freund/efeitos adversos , Hiperalgesia/genética , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Masculino , Camundongos , MicroRNAs/genética , Neuralgia/induzido quimicamente , Neuralgia/genética , Traumatismos dos Nervos Periféricos/genética , RNA Interferente Pequeno/genética , Fatores de Transcrição/genética , Transfecção/métodos
13.
World J Clin Cases ; 10(7): 2159-2165, 2022 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-35321190

RESUMO

BACKGROUND: Postmenopausal bleeding and an endometrial thickness ≥ 5 mm on sonograms of menopausal women can indicate the presence of endometrial lesions. Diagnostic hysteroscopy is a powerful method for endometrial diseases. AIM: To investigate the pathological pattern of endometrial abnormalities in postmenopausal women with bleeding or asymptomatic thickened endometrium diagnosed by hysteroscopy. METHODS: A total of 187 postmenopausal women with bleeding or asymptomatic thickened endometrium underwent diagnostic hysteroscopy. The women were subsequently divided into three groups: Postmenopausal bleeding (PMB) group (n = 84), asymptomatic group (n = 94), and additional group (n = 9). Women in the additional group manifested abdominal pain and leukorrhagia. RESULTS: Among the 187 patients examined, 84 (44.9%) were diagnosed with PMB and 94 (50.3%) with asymptomatic thickened endometrium. Endometrial polyp was the most common endometrial abnormality, which was detected in 51.2%, 76.6% and 77.8% of the PMB, asymptomatic, and additional groups, respectively. In the PMB group, 7 (8.3%) women had hyperplasia with atypia and 14 (16.7%) had endometrial adenocarcinoma. Fewer malignant lesions were detected in the asymptomatic group. Endometrial hyperplasia without atypia was found in 8.3% of the PMB group and 7.4% of the asymptomatic group. CONCLUSION: Endometrial polyp was the most common pathology in the PMB group. Diagnostic hysteroscopy is recommended for women with PMB and asymptomatic thickened endometrium.

14.
Artif Intell Med ; 125: 102255, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241259

RESUMO

Abnormal iron accumulation in the brain subcortical nuclei has been reported to be correlated to various neurodegenerative diseases, which can be measured through the magnetic susceptibility from the quantitative susceptibility mapping (QSM). To quantitatively measure the magnetic susceptibility, the nuclei should be accurately segmented, which is a tedious task for clinicians. In this paper, we proposed a dual-branch residual-structured U-Net (DB-ResUNet) based on 3D convolutional neural network (CNN) to automatically segment such brain gray matter nuclei. Due to memory limit, 3D-CNN-based methods typically adopted image patches, instead of the whole volumetric image, which, however, ignored the spatial contextual information of the neighboring patches, and therefore led to the accuracy loss. To better tradeoff segmentation accuracy and the memory efficiency, the proposed DB-ResUNet incorporated patches with different resolutions. By jointly using QSM and 3D T1 weighted imaging (T1WI) as inputs, the proposed method was able to achieve better segmentation accuracy over its single-branch counterpart, as well as the conventional atlas-based method and the classical 3D CNN structures. The susceptibility values and the volumes were also measured, which indicated that the measurements from the proposed DB-ResUNet was able to present high correlation with values from the manually annotated regions of interest.


Assuntos
Substância Cinzenta , Processamento de Imagem Assistida por Computador , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Redes Neurais de Computação
15.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(1): 72-80, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35300768

RESUMO

Objective To investigate the expression and the potential roles of long non-coding RNA(lncRNA)cancer susceptibility candidate 2(CASC2)and imprinted gene H19 in extrahepatic cholangiocarcinoma(ECC). Methods Four samples from patients with ECC were collected for high-throughput sequencing which was conducted to reveal the transcriptomic profiles of lncRNA CASC2 and H19.Bioinformatics tools were employed to predict the potential roles of the two genes.Another 22 ECC tissue samples and the cholangiocarcinoma cell lines(RBE,QBC939,HuH-28,and HuCCT1)with different degrees of differentiation were selected for validation.The para-carcinoma tissue and normal human intrahepatic biliary epithelial cell(HIBEC)were used as the control groups.The expression levels of lncRNA CASC2 and H19 in carcinoma tissue,para-carcinoma tissue,and cell lines were determined by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation analysis was carried out for the clinical indicators of patients with the expression levels of the target genes. Results The two target genes showed significantly different expression between carcinoma tissue and para-carcinoma tissue(all P<0.05).Specifically,CASC2 had higher expression level in the carcinoma tissue than in the para-carcinoma tissue(t=1.262,P=0.025),whereas the expression of H19 showed an opposite trend(t=1.285,P=0.005).The expression levels of CASC2 in QBC939(t=8.114,P=0.015)and HuH-28(t=9.202,P=0.012)cells were significantly higher than that in the control group.The expression levels of H19 were significantly lower in RBE(t=-10.244,P<0.001),QBC939(t=-10.476,P<0.001),HuH-28(t=-19.798,P<0.001),and HuCCT1(t=-16.193,P=0.004)cells than in the control group.Bioinformatics analysis showed that CASC2 was mainly involved in the metabolic process and H19 in the development of multicellular organisms.Both CASC2 and H19 were related to catalytic activity.The expression level of lncRNA CASC2 was correlated with pathological differentiation(χ 2=6.222,P=0.022)and lymph node metastasis(χ2=5.455,P=0.020),and that of lncRNA H19 with pathological differentiation(χ2=1.174,P=0.029)and tumor size(χ2=-0.507,P=0.037). Conclusions In the case of ECC,lncRNA CASC2 and H19 have transcription disorders.lncRNA CASC2 is generally up-regulated in the carcinoma tissue,while H19 is down-regulated.Both genes have the potential to become new molecular markers for ECC.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , RNA Longo não Codificante , Proteínas Supressoras de Tumor , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/metabolismo , Colangiocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Longo não Codificante/genética , Proteínas Supressoras de Tumor/genética
16.
Toxicology ; 469: 153114, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35114310

RESUMO

Silicosis is the most serious occupational pulmonary fibrosis caused by excessive inhalation of silica particles, whereas viable therapeutic choices are constrained. Epigallocatechin gallate (EGCG) presents massive health benefits, but unfortunately with stability absence. Here, encapsulation of EGCG in poly(n-butylcyanoacrylate) nanoparticles (EGCG/PBCA-NPs) were fabricated by self-polymerization for gastrointestinal delivery in silicosis fibrosis treatment. The obtained nano-enabled delivery of EGCG was produced using a medical adhesive approved by FDA as carrier, and presented spherical particles with approximate diameter of 160 nm, a narrow PDI value of 0.2, Zeta potential value of 30 mV as well as a high EGCG incorporation (90 %) and loading efficiency (20 %). In evaluating the protect effects of nano-formulations, EGCG/PBCA-NPs shown excellent stability in gastric fluid with pH-triggered release in intestine and strong EGCG gastrointestinal retention against degradation. After daily gastrointestinal administration, EGCG/PBCA-NPs exhibited the superior anti-fibrosis efficacy in silicosis model rats induced by silica, involving lung index decline, hydroxyproline content decrease, histological improvement, collagen accumulation reduction and α-SMA down-regulation in comparison with naked EGCG. These results strongly demonstrated that PBCA-based NPs may be a promising nano-enabled delivery carrier for enhancing the gastrointestinal stability and anti-fibrotic effects of EGCG.


Assuntos
Catequina , Nanopartículas , Fibrose Pulmonar , Silicose , Animais , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/uso terapêutico , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/prevenção & controle , Ratos , Dióxido de Silício/toxicidade , Silicose/tratamento farmacológico
17.
Int J Biol Macromol ; 204: 410-418, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35150779

RESUMO

Curcumin (Cur) exhibits low water solubility and insufficient dispersibility in food systems, and cannot exert its excellent antioxidant properties. In this work, Chitosan (CS) nanoparticles were prepared by ionic crosslinking method using chitosan as carrier and sodium tripolyphosphate (TPP) as crosslinking agent, then Cur was loaded to obtain curcumin nanoparticles (CNPs). CNPs presented a spherical morphology with average size of 278.9 nm. Compared with the solubility of native Cur (0.017 µg/mL) at 25 °C, the water solubility of CNPs increased to 35.92 µg/mL of more than 2100 times. In addition, the antioxidant capacity of Cur was also studied based on DPPH free radical scavenging, the results showed that with the increase of the concentration, the antioxidant capacity of CNPs was significantly increased (p < 0.05), which was higher than that of Cur at the same concentration. The edible coating was prepared by adding CNPs into sodium carboxymethyl cellulose (CMC) to study the effects of CMC-CNPs coatings in improving the quality and shelf life of fresh pork stored at 4 ± 1 °C for 15 days. The results showed that CMC-CNPs edible coating could significantly inhibit lipid oxidation of fresh pork (p < 0.05) and could be further applied in lipid rich food packaging.


Assuntos
Quitosana , Curcumina , Filmes Comestíveis , Nanopartículas , Carne de Porco , Carne Vermelha , Animais , Antioxidantes/farmacologia , Quitosana/química , Curcumina/química , Curcumina/farmacologia , Nanopartículas/química , Tamanho da Partícula , Suínos
18.
Artigo em Inglês | MEDLINE | ID: mdl-35212776

RESUMO

PURPOSE: To establish and validate a radiomics signature for stratifying the risk of progression-free survival (PFS) in patients with locally advanced hypopharyngeal carcinoma (LAHC) undergoing induction chemotherapy (IC). METHODS: We extracted radiomics features from baseline contrast-enhanced computed tomography (CECT) images. We enrolled 112 LAHC patients (78 in the training cohort and 34 in the validation cohort). We used cox regression model and random survival forests variable hunting (RSFVH) algorithm for feature selection and radiomics signature building. The radiomics signature was established in the training cohort and tested in the validation cohort. We used the Kaplan-Meier analysis and log-rank test to evaluate the ability of radiomics signature in PFS risk stratification among patients with different IC responses and constructed a radiomics nomogram to predict individual PFS risk. RESULTS: The radiomics signature performed well in stratifying patients into highrisk and low-risk groups of progression in both the training and validation cohorts. The radiomics nomogram showed good discriminative ability for predicting PFS. Survival outcome analysis of subsets indicated that the radiomics signature performed well in stratifying the risk of PFS in patients with LAHC with different IC responses. CONCLUSIONS: The radiomics signature was a pretreatment predictor for PFS in patients with LAHC who exhibited different responses to IC.

19.
World J Clin Cases ; 10(1): 166-176, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35071516

RESUMO

BACKGROUND: Tissue resident memory T (TRM) cells have been reported to play a significant role in the pathogenesis and relapse of chronic eczema. AIM: To compare the efficacy and safety of the intralesional injection of 5-fluorouracil (5-FU) and triamcinolone (TA) with those associated with TA alone for the treatment of chronic eczema. METHODS: A total of 168 patients were randomized to 5-FU+TA or TA groups and received a one-time intralesional injection of 5-FU+TA or TA only. Biopsies were collected before and 2 wk after treatment for evaluation of histopathological changes. All patients were followed up monthly for up to 1 year. RESULTS: No serious adverse event was observed in either group. Although the mean atopic dermatitis severity index scores and effective rates were comparable between the two groups after 2 wk of treatment, the relapse rate was significantly lower in the 5-FU+TA group than in the TA group. Histological examination showed significantly fewer CD8+ and CD103+ T cells but not CD4+ T cells in the 5-FU+TA group. CONCLUSION: One-time intralesional injection of 5-FU+TA is effective and safe for chronic eczema treatment and can further reduce the retention of TRM cells in the lesional skin and the relapse rate of chronic eczema.

20.
Diagnostics (Basel) ; 12(1)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35054370

RESUMO

Bladder cancer has been increasing globally. Urinary cytology is considered a major screening method for bladder cancer, but it has poor sensitivity. This study aimed to utilize clinical laboratory data and machine learning methods to build predictive models of bladder cancer. A total of 1336 patients with cystitis, bladder cancer, kidney cancer, uterus cancer, and prostate cancer were enrolled in this study. Two-step feature selection combined with WEKA and forward selection was performed. Furthermore, five machine learning models, including decision tree, random forest, support vector machine, extreme gradient boosting (XGBoost), and light gradient boosting machine (GBM) were applied. Features, including calcium, alkaline phosphatase (ALP), albumin, urine ketone, urine occult blood, creatinine, alanine aminotransferase (ALT), and diabetes were selected. The lightGBM model obtained an accuracy of 84.8% to 86.9%, a sensitivity 84% to 87.8%, a specificity of 82.9% to 86.7%, and an area under the curve (AUC) of 0.88 to 0.92 in discriminating bladder cancer from cystitis and other cancers. Our study provides a demonstration of utilizing clinical laboratory data to predict bladder cancer.

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