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1.
Front Immunol ; 13: 840811, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35515000

RESUMO

Background: The tumor microenvironment (TME) plays a pivotal role in cancer progression in papillary thyroid carcinoma (PTC), yet the composition and the phenotype of cells within the TME in bilateral PTC are poorly understood. Methods: We performed unbiased transcriptome-wide single-cell RNA sequencing (scRNA-seq) analysis on 29,561 cells from 3 pairs of bilateral PTC and 1 non-tumor thyroid sample. The results of the analysis were validated by a large-scale bulk transcriptomic dataset deposited in The Cancer Genome Atlas (TCGA) database. Results: Our integrative analysis of thyroid follicular cells revealed 42 signaling pathways enriched in malignant follicular cells, including cytokine-cytokine receptor interaction, PI3K/Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. A 6-gene signature (CXCL3, CXCL1, IL1A, CCL5, TNFRSF12A, and IL18) in the cytokine-cytokine receptor interaction pathway was constructed to predict the prognosis of patients with PTC, with high risk scores being associated with decreased overall survival [hazard ratio (HR) = 3.863, 95% CI = 2.233-6.682, p < 0.001]. Gene set variation analysis (GSVA) indicated that the pathways enriched in bilateral PTC were significantly different, indicating great heterogeneity in bilateral PTC, even with the same BRAF V600E mutation. Comprehensive analysis of T cells revealed that the proportion of CD8+ tissue-resident memory T cells expressing IFNG decreased in tumor samples with advanced N stage. Within the myeloid compartment, the ratio of suppressive M2-like to pro-inflammatory M1-like macrophages increased with advanced disease stage, which was confirmed in the bulk dataset using transcriptomic profiles. In addition, we also identified numerous biologically critical interactions among myeloid cells, T cells, and follicular cells, which were related to T-cell recruitment, M2-like macrophage polarization, malignant follicular cell progression, and T-cell inhibitory signaling. Conclusion: Our integrative analyses revealed great inter-tumor heterogeneity within the TME in bilateral PTC, which will offer assistance for precise diagnosis and treatment.


Assuntos
Neoplasias da Glândula Tireoide , Transcriptoma , Citocinas/genética , Perfilação da Expressão Gênica , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Receptores de Citocinas/genética , Análise de Célula Única , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Microambiente Tumoral/genética
2.
Nanomicro Lett ; 14(1): 124, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543758

RESUMO

Triboelectric nanogenerators (TENGs) have shown promising potential for large-scale blue energy harvesting. However, the lack of reasonable designs has largely hindered TENG from harvesting energy from both rough and tranquil seas. Herein, a fully symmetrical triboelectric nanogenerator based on an elliptical cylindrical structure (EC-TENG) is proposed for all-weather blue energy harvesting. The novel elliptical cylindrical shell provides a unique self-stability, high sensitivity to wave triggering, and most importantly, an anti-overturning capability for the EC-TENG. Moreover, benefiting from its internal symmetrical design, the EC-TENG can produce energy normally, even if it was overturned under a rude oscillation in the rough seas, which distinguishes this work from previous reported TENGs. The working mechanism and output performance are systematically studied. The as-fabricated EC-TENG is capable of lighting 400 light-emitting diodes and driving small electronics. More than that, an automatic monitoring system powered by the EC-TENG can also monitor the water level in real-time and provide an alarm if necessary. This work presents an innovative and reliable approach toward all-weather wave energy harvesting in actual marine environments.

3.
Front Immunol ; 13: 731516, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242126

RESUMO

Exosomes are nanoscale extracellular vesicles (EVs), which are present in all body fluids tested. They are secreted by a variety of cells including macrophages, dendritic cells, mast cells, granulocytes, lymphocytes, and tumor cells. Exosomes secreted by different cells have different biological components and functional characteristics and play an important role in many pathophysiological activities. Recent studies have revealed that exosomes can regulate the occurrence and development of inflammatory immune diseases and tumors by transmitting their unique proteins, lipids, and nucleic acids as signaling molecules to other cells. Exosomes serve as a novel class of diagnostic biomarkers and drug delivery systems with promising applications in immunotherapy, particularly because breakthroughs in nanotechnology have led to the development and exploration of engineered exosomes for immunotargeted therapies. Therefore, here we review the progress being made on the application of exosomes in immunotherapy and its multiple regulatory mechanisms and explore the potential application of exosomes in immunotherapy in the future.


Assuntos
Exossomos , Vesículas Extracelulares , Neoplasias , Sistemas de Liberação de Medicamentos , Exossomos/metabolismo , Vesículas Extracelulares/patologia , Humanos , Imunoterapia , Neoplasias/patologia
4.
Jpn J Infect Dis ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35354706

RESUMO

Novel immunodominant antigens are urgently required for diagnosis and vaccine of Helicobacter pylori(HP). FliD, an important colonization factor was cloned and expressed(rFliD) to evaluate the levels of specific-IgG, IgM and IgA antibodies in the serum of patients by ELISA. Rabbit anti-rFliD polyclonal antibody (pAb) was obtained by subcutaneous injections of rFliD. The rFliD-specific IFN-γ and IL-4 of peripheral blood mononuclear cells and CD4+ T cells from human were analyzed by enzyme-linked immunospot and flow cytometry. We found that the levels of rFliD-specific IgG, IgM and IgA were significantly higher in HP-infected-patients compared with healthy controls. IgG, IgM and IgA had diagnostic sensitivities of 92.6, 89.8 and 83.2%; specificities of 91.1, 88.7 and 64.6%; and areas under the receiver operating curves of 0.97, 0.96 and 0.92, respectively. Furthermore, rFliD-pAb was used in the immunohistochemical analysis of gastritis and gastric cancer tissues from patients infected with HP. The levels of rFliD-specific IFN-γ and IL-4 were significantly elevated in HP-infected patients and exhibited a T helper type 1-dominant subtype. These findings indicate that rFliD exhibits high validity as a biomarker in HP diagnosis and may also be a potent antigen for vaccine design due to its high cellular and humoral immune response.

5.
Nutrients ; 14(5)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35267955

RESUMO

BACKGROUND: This study aimed to identify lipid metabolism-related dietary patterns with reduced rank regression (RRR) among Chinese adults and examine their associations with incident diabetes. METHODS: We derived lipid metabolism-related dietary patterns using an RRR with 21 food groups as predictors as well as total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, body mass index (BMI), and waist circumference from the responses of 17,318 participants from the second resurvey of the China Kadoorie Biobank (CKB). The dietary scores were calculated for the entire cohort. We followed up 479,207 participants for diabetes incidence from the baseline and used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Two lipid metabolism-related dietary patterns were extracted. The dietary pattern-characterized by high intakes of fish, poultry, and other staples as well as fresh fruit and vegetables-was correlated with a higher BMI, waist circumference, and LDL cholesterol. Participants in the highest quintile (Q5) had a 44% increased risk of diabetes incidence when compared with those in the lowest quintile (Q1) (HR = 1.44; 95% CI: 1.31-1.59). CONCLUSIONS: A dietary pattern characterized by high intakes of both animal and plant foods was related to obesity and dyslipidemia and could increase the risk of diabetes incidence.


Assuntos
Diabetes Mellitus , Metabolismo dos Lipídeos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Dieta/efeitos adversos , Humanos , Verduras
6.
Front Plant Sci ; 13: 814059, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35283932

RESUMO

As an individual plant species can develop its own leaf stoichiometry to adapt to environmental changes, this stoichiometry can provide critical information about a plant species' growth and its potential management in the ecosystem housing it. However, leaf stoichiometry is largely undocumented in regions with large environmental changes arising from differences in elevation. The leaf stoichiometry of Potentilla fruticosa L., a major alpine shrub playing an important role in supporting ecosystem functions and services in China's Qilian Mountains (Northeast Qinghai-Tibetan Plateau), was investigated at different elevations (2,400, 2,600, 2,800, 3,000, 3,200, 3,500, and 3,800 m). At each elevation, leaf elemental (C, N, and P) concentrations were measured in P. fruticosa leaves sampled from three plots (10 × 10 m), and edaphic properties were assessed in nine quadrats (1 × 1 m, three quadrats per plot). Temperature and precipitation were calculated using an empirical formula. Maximum and minimum leaf carbon (C) concentrations ([C] leaf ) of 524 ± 5.88 and 403 ± 3.01 g kg-1 were measured at 2,600 and 3,500 m, respectively. Leaf nitrogen (N) concentration ([N] leaf ) showed a generally increasing trend with elevation and peaked at 3,500 m (27.33 ± 0.26 g kg-1). Leaf phosphorus (P) concentration ([P] leaf ) varied slightly from 2,400 to 3,200 m and then dropped to a minimum (0.60 ± 0.10 g kg-1) at 3800 m. The [C] leaf :[N] leaf , [C] leaf :[P] leaf , and [N] leaf :[P] leaf varied little from 2,400 to 3,000 m but fluctuated somewhat at higher elevations. The main factors affecting P. fruticosa leaf stoichiometry were soil organic C, pH, and soil total P, and the main limiting element for the growth of P. fruticosa in the study area was P. In conclusion, changes in elevation affected leaf stoichiometry of P. fruticosa mainly due to altered soil properties, and addressing phosphorus limitation, especially at higher elevations mainly due to losses caused by high precipitation and sparse vegetation, is a key measure to promote P. fruticosa growth in this region.

7.
World J Microbiol Biotechnol ; 38(4): 71, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35258706

RESUMO

The present study aimed to evaluate transcriptional activator-like effector (TALE) genes in 86 Xanthomonas oryzae pv. oryzicola strains collected from 8 rice-growing regions in Yunnan, and to examine the relationship between TALE genotypes and virulence in 6 differential rice lines. Besides, the geographical areas, distribution of these genotypes were studied in detail. Genetic diversity was analyzed through the number and size of putative TALE genes based on TALE gene avrXa3 as a probe. We found that X. oryzae pv. oryzicola strains consist of variable number (13-27) of avrXa3-hybridizing fragments (putative TALE genes). Test strains were classified into 8 genotypes (G1-G8) with major genotypes G3 and G7 widely distributed in Yunnan. Pathogenicity of X. oryzae pv. oryzicola was evaluated by inoculating 6 differential rice lines with a single resistance gene into 9 pathotypes clusters (I-IX), the dominant Genotypes G3 and G7 consist of pathotypes I, II, and IV. Furthermore, we also detected the known TALE target genes expression in susceptible rice cultivar (cv. nipponbare) after inoculating 8 genotypes-representative X. oryzae pv. oryzicola strain. Correlation between the numbers of putative TALE genes of X. oryzae pv. oryzicola and relevant target genes in nipponbare confirmed up-regulation. Altogether, this study has given insights into the population structure of X. oryzae pv. oryzicola that may inform strategies to control BLS in rice.


Assuntos
Oryza , Xanthomonas , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , China , DNA Bacteriano/genética , Oryza/genética , Doenças das Plantas , Folhas de Planta/metabolismo , Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Virulência/genética , Xanthomonas/genética
8.
J Colloid Interface Sci ; 617: 604-610, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35305472

RESUMO

Two-dimensional nanomaterials have been incorporated into coating layers for exceptional properties in mechanic toughness, electronics, thermology and optics. Graphene oxide (GO), however, was greatly hindered by its strong adsorption within visible wavelength and hereby the intrinsic dark color at the solid state. Herein, we found a unique aqueous mixture of GO containing sodium dodecyl sulfate and l-ascorbic acid. It enabled to produce iridescent coating layers with tunable thickness of 0.3-50 µm on both hydrophilic and hydrophobic substrates (e.g., glass, aluminum foil, polytetrafluoroethylene), through brushing, liquid-casting, dipping and writing. Their iridescence could be further tuned by incorporating MXene nanosheets. And their mechanical properties could be enhanced by certain synthetic polymers (e.g., polyvinyl alcohol and polyethylene glycol). Their sensitivity to heat, laser and water also benefited to pattern the coating layers. Furthermore, by controlling laser intensity, the domain color could be changed (e.g., green to blue). Thus, this study may pave a new pathway of producing iridescent coatings of graphene oxide in a large scale for practical applications.


Assuntos
Grafite , Iridescência , Adsorção , Grafite/química , Interações Hidrofóbicas e Hidrofílicas , Água
9.
Front Surg ; 9: 838879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35187063

RESUMO

OBJECTIVE: To analyze the therapeutic effect of uterine artery embolisation (UAE) in patients with cesarean section pregnancy (CSP) delivered by cesarean section and the effect on serum human chorionic gonadotrophin (ß-HCG) levels and reproductive function. METHODS: In total 142 patients with CSP, The control group (n = 71) received Methotrexate (MTX) with ultrasound monitoring after admission and the research group (n = 71) was treated with UAE on basic of the control group. The two groups were compared in terms of treatment outcome, intraoperative bleeding, bed activity, vaginal bleeding and length of hospital stay, and serum follicle stimulating hormone (FSH), oestradiol (E2), luteinising hormone (LH) and ß-HCG levels at 1 month postoperatively. The clinical symptoms (normalization of ß-HCG and return of menstruation) and clinical outcomes (normal pregnancy, recurrent scar pregnancy) were compared between the two groups, as well as the occurrence of post-operative complications in both groups. RESULTS: Compared with the control group, the research group had a higher overall near-term effective rate, a lower recurrence rate of CSP in pregnancy, and a lower complication rate (P < 0.05); meanwhile, the time to get out of bed, postoperative vaginal bleeding, length of hospital stay, normalization of serum ß-HCG, and return to menstruation were shorter in the research group than in the control group (P < 0.05); In addition, serum FSH, E2, LH and ß-HCG levels improved better in the research group compared with the control group 1 month after surgery (P < 0.05). CONCLUSION: The treatment of CSP patients with UAE can reduce the amount of intraoperative bleeding and the duration of vaginal bleeding, promote the improvement of patients' clinical symptoms, have less impact on the disruption of patients' sex hormone balance, reduce patients' surgical risks to a greater extent, preserve patients' normal fertility, and have better application.

10.
Behav Sci (Basel) ; 12(2)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35200270

RESUMO

The global importance of English and therefore the teaching of the English language has made the English language curriculum an integral part of all levels of teacher education, including early childhood education. The purpose of this study was to first explore the beliefs about the teaching of English to very young learners held by pre-service pre-primary teachers in Macau and then to see whether these beliefs were reflected in their microteaching. Qualitative content analysis performed on the written reflections and transcriptions of the microteaching videos of 75 pre-service pre-primary teachers found that their beliefs about classroom practices, lesson planning, and English as a foreign language (EFL) learners and learning were the most predominant beliefs exhibited in their reflections and were evidenced in their microteaching. Less predominant, but still salient, were their beliefs about the goals of language learning, assessment, teaching, pedagogical knowledge, and content. No observable practices were found regarding the pre-service teachers' beliefs about the role of teaching, learning to teach, microteaching, the self, the subject, hearsay, self-assessment, and schooling. The current study found that with only limited exposure to EFL teaching methodology from a single course, the pre-service pre-primary teachers were able to implement some of their beliefs about several important aspects of teaching English to very young learners.

11.
Gastroenterology ; 162(7): 1948-1961.e7, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35202643

RESUMO

BACKGROUND & AIMS: Hepatocellular nodular lesions (HNLs) constitute a heterogeneous group of disorders. Differential diagnosis among these lesions, especially high-grade dysplastic nodules (HGDNs) and well-differentiated hepatocellular carcinoma (WD-HCC), can be challenging, let alone biopsy specimens. We aimed to develop a deep learning system to solve these puzzles, improving the histopathologic diagnosis of HNLs (WD-HCC, HGDN, low-grade DN, focal nodular hyperplasia, hepatocellular adenoma), and background tissues (nodular cirrhosis, normal liver tissue). METHODS: The samples consisting of surgical and biopsy specimens were collected from 6 hospitals. Each specimen was reviewed by 2 to 3 subspecialists. Four deep neural networks (ResNet50, InceptionV3, Xception, and the Ensemble) were used. Their performances were evaluated by confusion matrix, receiver operating characteristic curve, classification map, and heat map. The predictive efficiency of the optimal model was further verified by comparing with that of 9 pathologists. RESULTS: We obtained 213,280 patches from 1115 whole-slide images of 738 patients. An optimal model was finally chosen based on F1 score and area under the curve value, named hepatocellular-nodular artificial intelligence model (HnAIM), with the overall 7-category area under the curve of 0.935 in the independent external validation cohort. For biopsy specimens, the agreement rate with subspecialists' majority opinion was higher for HnAIM than 9 pathologists on both patch level and whole-slide images level. CONCLUSIONS: We first developed a deep learning diagnostic model for HNLs, which performed well and contributed to enhancing the diagnosis rate of early HCC and risk stratification of patients with HNLs. Furthermore, HnAIM had significant advantages in patch-level recognition, with important diagnostic implications for fragmentary or scarce biopsy specimens.

12.
Environ Sci Technol ; 56(4): 2519-2528, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35075897

RESUMO

3,3',5,5'-Tetrabromobiphenyl (BB-80) was once used as additive flame retardants. Whether its early exposure and discontinued exposure alter thyroid function remains unknown. We investigate adverse effects after early-life exposure and discontinued exposure to BB-80 and hydroxylated BB-80 (OH-BB-80) on thyroid hormone (TH) levels, thyroid tissue, and transcriptome profiles in zebrafish larvae. BB-80 at 10 µg/L induces pathological changes of thyroid with reduced thyroid follicles in larvae (P < 0.05), whereas OH-BB-80 significantly increases T4 and T3 contents (1.8 and 2.5 times of the control, P < 0.05) at 14 days postfertilization (dpf) without morphological thyroid alterations. BB-80 and OH-BB-80 cause transcriptome aberrations with key differentially expressed genes involved in the disruption of TH synthesis and signal transduction (BB-80 at 14 dpf) or TH pathway activation (OH-BB-80 at 21 dpf). After 7 days of discontinued exposure, thyroglobulin (tg) and thyroid peroxidase (tpo) genes are downregulated (P < 0.05) by 52 and 48% for BB-80 and by 49 and 39% for OH-BB-80, respectively; however, the whole-body TH levels fail to fully recover, and the locomotor activity is impaired more by BB-80. Our results indicate significant adverse impacts of BB-80 and OH-BB-80 on TH homeostasis and thyroid function of zebrafish.


Assuntos
Retardadores de Chama , Poluentes Químicos da Água , Animais , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Larva/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
13.
Virchows Arch ; 480(2): 259-267, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34562173

RESUMO

Glutaminase 1 (GLS) is a therapeutic target for breast cancer; although GLS inhibitors have been developed, only a few subjects responded well to the therapy. Considering that the expression of histone H3 lysine 27 trimethylation (H3K27me3) and menopausal status was closely linked to GLS, we examined the effects of H3K27me3 and menopausal status on GLS to breast cancer prognosis. Data for 962 women diagnosed with primary invasive breast cancer were analyzed. H3K27me3 and GLS expression in tumors were evaluated with tissue microarrays by immunohistochemistry. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival and progression-free survival were estimated using Cox regression models. Statistical interaction was assessed on multiplicative scale. There was a beneficial prognostic effect of GLS expression on overall survival for those with low H3K27me3 level (HR = 0.50, 95% CI: 0.20-1.28) but an adverse prognostic effect for those with high H3K27me3 level (HR = 3.90, 95% CI: 1.29-11.78) among premenopausal women, and the statistical interaction was significant (Pinteraction = 0.003). Similar pattern was further observed for progression-free survival (HR = 0.44, 95% CI: 0.20-0.95 for low H3K27me3 level, HR = 1.35, 95% CI: 0.74-2.48 for high H3K27me3 level, Pinteraction = 0.024). The statistical interaction did not occur among postmenopausal women. Our study showed that the prognostic effects of GLS on breast cancer correlated to the expression level of H3K27me3 and menopausal status, which would help optimize the medication strategies of GLS inhibitors.


Assuntos
Neoplasias da Mama , Histonas , Neoplasias da Mama/patologia , Feminino , Glutaminase , Histonas/metabolismo , Humanos , Menopausa , Prognóstico
14.
J Endocrinol ; 252(3): 179-193, 2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-34874016

RESUMO

Compelling evidence has described that the incidence of hypertension and left ventricular hypertrophy (LVH) in postmenopausal women is significantly increased worldwide. Our team's previous research identified that androgen was an underlying factor contributing to increased blood pressure and LVH in postmenopausal women. However, little is known about how androgens affect LVH in postmenopausal hypertensive women. The purpose of this study was to evaluate the role of mammalian rapamycin receptor (mTOR) signaling pathway in myocardial hypertrophy in androgen-induced postmenopausal hypertension and whether mTOR inhibitors can protect the myocardium from androgen-induced interference to prevent and treat cardiac hypertrophy. For that, ovariectomized (OVX) spontaneously hypertensive rats (SHR) aged 12 weeks were used to study the effects of testosterone (T 2.85 mg/kg/weekly i.m.) on blood pressure and myocardial tissue. On the basis of antihypertensive therapy (chlorthalidone 8 mg/kg/day ig), the improvement of blood pressure and myocardial hypertrophy in rats treated with different dose gradients of rapamycin (0.8 mg/kg/day vs 1.5 mg/kg/day vs 2 mg/kg/day i.p.) in OVX + estrogen (E 9.6 mg/kg/day, ig) + testosterone group was further evaluated. After testosterone intervention, the OVX female rats exhibited significant increments in the heart weight/tibial length (TL), area of cardiomyocytes and the mRNA expressions of ANP, ß-myosin heavy chain and matrix metalloproteinase 9 accompanied by a significant reduction in the uterine weight/TL and tissue inhibitor of metalloproteinase 1. mTOR, ribosomal protein S6 kinase (S6K1), 4E-binding protein 1 (4EBP1) and eukaryotic translation initiation factor 4E in myocardial tissue of OVX + estrogen + testosterone group were expressed at higher levels than those of the other four groups. On the other hand, rapamycin abolished the effects of testosterone-induced cardiac hypertrophy, decreased the systolic and diastolic blood pressure of SHR, and inhibited the activation of mTOR/S6K1/4EBP1 signaling pathway in a concentration-dependent manner. Collectively, these data suggest that the mTOR/S6K1/4EBP1 pathway is an important therapeutic target for the prevention of LVH in postmenopausal hypertensive female rats with high testosterone levels. Our findings also support the standpoint that the mTOR inhibitor, rapamycin, can eliminate testosterone-induced cardiomyocyte hypertrophy.


Assuntos
Hipertrofia Ventricular Esquerda/prevenção & controle , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Miocárdio/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Hipertrofia Ventricular Esquerda/etiologia , Ovariectomia , Ratos Endogâmicos SHR , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Testosterona
15.
Clin Mol Hepatol ; 28(2): 183-195, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34839623

RESUMO

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. METHODS: We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. RESULTS: Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42-0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45-0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. CONCLUSION: The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.


Assuntos
/genética , Hepatopatia Gordurosa não Alcoólica , Predisposição Genética para Doença , Humanos , Lipase/genética , Fígado/patologia , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único , Vitamina D/metabolismo
16.
Clin Gastroenterol Hepatol ; 20(3): e573-e582, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33618024

RESUMO

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology updated from non-alcoholic fatty liver disease (NAFLD). In this study, we aim to estimate the global prevalence of MAFLD specifically in overweight and obese adults from the general population by performing a systematic review and meta-analysis through mining the existing epidemiological data on fatty liver disease. METHODS: We searched Medline, Embase, Web of Science, Cochrane and google scholar database from inception to November, 2020. DerSimonian-Laird random-effects model with Logit transformation was performed for data analysis. Sensitivity analysis and meta-regression were used to explore predictors of MAFLD prevalence in pooled statistics with high heterogeneity. RESULTS: We identified 116 relevant studies comprised of 2,667,052 participants in general population with an estimated global MAFLD prevalence as 50.7% (95% CI 46.9-54.4) among overweight/obese adults regardless of diagnostic techniques. Ultrasound was the most commonly used diagnostic technique generating prevalence rate of 51.3% (95% CI, 49.1-53.4). Male (59.0%; 95% CI, 52.0-65.6) had a significantly higher MAFLD prevalence than female (47.5%; 95% CI, 40.7-54.5). Interestingly, MAFLD prevalence rates are comparable based on classical NAFLD and non-NAFLD studies in general population. The pooled estimate prevalence of comorbidities such as type 2 diabetes and metabolic syndrome was 19.7% (95% CI, 12.8-29.0) and 57.5% (95% CI, 49.9-64.8), respectively. CONCLUSIONS: MAFLD has an astonishingly high prevalence rate in overweight and obese adults. This calls for attention and dedicated action from primary care physicians, specialists, health policy makers and the general public alike.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Adulto , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Prevalência
17.
Biol Trace Elem Res ; 200(5): 2268-2282, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34347232

RESUMO

In order to evaluate the effects of lanthanum nitrate on the development of the parent, offspring, and the third generation of Sprague-Dawley (SD) rats, a two-generation reproductive toxicity experiment, was conducted. Two hundred and forty specific pathogen-free (SPF) healthy SD rats were randomly divided into the control group, low-, medium-, and high-dose group, with 30 male and 30 female rats in each group. The rats in each group were given 0 mg/kg, 10.0 mg/kg, 30.0 mg/kg, and 90.0 mg/kg lanthanum nitrate by gavage, respectively. There was no statistically significant difference between the weight gain and food intake of rats in each group. High-dose lanthanum nitrate had no effect on rat implantation and no embryo toxicity. The absolute and relative liver weights of F1a and F1b male rats in the high-dose group were significantly decreased. The absolute liver and spleen weight of F1b female rats in the high-dose group decreased significantly, but the relative weight did not change significantly. Histopathological examination results showed that there were no significant differences in the effects of different doses of lanthanum nitrate on the uterus, ovaries, oviduct, testes and epididymis, and liver of SD rats. Under the experimental conditions, 90.0 mg/kg lanthanum nitrate had an effect on the liver weight of the SD rats, but there was no liver toxicity. The no visible harmful effect level (NOAEL) of lanthanum nitrate on SD rats' reproduction toxicity is 90 mg/kg.


Assuntos
Reprodução , Animais , Peso Corporal , Relação Dose-Resposta a Droga , Feminino , Lantânio , Masculino , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley
18.
Br J Radiol ; 95(1129): 20201302, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34767476

RESUMO

OBJECTIVE: To evaluate the diagnostic performance of a radiomics model based on multiregional and multiparametric MRI to classify paediatric posterior fossa tumours (PPFTs), explore the contribution of different MR sequences and tumour subregions in tumour classification, and examine whether contrast-enhanced T1 weighted (T1C) images have irreplaceable added value. METHODS: This retrospective study of 136 PPFTs extracted 11,958 multiregional (enhanced, non-enhanced, and total tumour) features from multiparametric MRI (T1- and T2 weighted, T1C, fluid-attenuated inversion recovery, and diffusion-weighted images). These features were subjected to fast correlation-based feature selection and classified by a support vector machine based on different tasks. Diagnostic performances of multiregional and multiparametric MRI features, different sequences, and different tumoral regions were evaluated using multiclass and one-vs-rest strategies. RESULTS: The established model achieved an overall area under the curve (AUC) of 0.977 in the validation cohort. The performance of PPFTs significantly improved after replacing T1C with apparent diffusion coefficient maps added into the plain scan sequences (AUC from 0.812 to 0.917). When oedema features were added to contrast-enhancing tumour volume, the performance did not significantly improve. CONCLUSION: The radiomics model built by multiregional and multiparametric MRI features allows for the excellent distinction of different PPFTs and provides valuable references for the rational adoption of MR sequences. ADVANCES IN KNOWLEDGE: This study emphasized that T1C has limited added value in predicting PPFTs and should be cautiously adopted. Selecting optimal MR sequences may help guide clinicians to better allocate acquisition sequences and reduce medical costs.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias Infratentoriais/diagnóstico por imagem , Imageamento por Ressonância Magnética Multiparamétrica , Área Sob a Curva , Criança , Meios de Contraste , Feminino , Humanos , Neoplasias Infratentoriais/classificação , Neoplasias Infratentoriais/patologia , Masculino , Gradação de Tumores , Estudos Retrospectivos
19.
Mater Horiz ; 9(2): 780-790, 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-34901984

RESUMO

Controllable liquid transportation through a smart porous membrane is realized by manipulating the surface wetting properties and external stimuli, and has been intensively studied. However, the liquid transportation, e.g., permeation and moving process, at the interface is generally uninterrupted, i.e., the opening and closing of the interface is irreversible. Herein, we present a new strategy to achieve magnetic adaptive switchable surfaces, i.e., liquid-infused micro-nanostructured porous composite film surfaces, for controllable liquid transportation, via modulation of the magnetic field. The liquid transportation process can be interrupted and restarted on the porous composite film because its pore structure can be quickly closed and opened owing to the adaptive morphological transformation of the magnetic liquid with a varying magnetic field. That is, the liquid permeation process occurs due to the open pore structure of the composite film when the external magnetic field is added, while the permeation process can be interrupted owing to the self-repairing closure of the pore when the magnetic field is removed, and the moving process can be achieved. Thus a magnetic field induced switchable porous composite film can serve as a valve to control liquid permeation based transportation, which opens new avenues for artificial liquid gating devices for flow, smart separation, and droplet microfluidics.

20.
Clin Epigenetics ; 13(1): 213, 2021 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863285

RESUMO

BACKGROUND: Cortisol-producing adrenocortical adenoma (CPA) during pregnancy rarely occurs in clinic. Growing evidence suggests that DNA methylation plays a key role in adrenocortical adenomas. The present study aims to examine the genome-wide DNA methylation profiles and identify the differences in DNA methylation signatures of non-pregnant and pregnant patients with CPA. RESULTS: Four pregnant and twelve non-pregnant patients with CPA were enrolled. The pregnant patients with CPA had higher serum cortisol, Estradiol, Progesterone, and human chorionic gonadotropin concentration, while having lower serum FSH (follicle-stimulating hormone) and luteinizing hormone concentrations (P < 0.01). Compared with the non-pregnant patients, the duration is shorter, and the growth rate of the tumor is faster in pregnant patients with CPA (P < 0.05). Morphology and cell proliferation assay showed that the percentage of Ki-67 positive cells in CPA were higher in pregnant group than non-pregnant group (8.0% vs 5.5%, P < 0.05). The DNA methylation analysis showed that Genome-wide DNA methylation signature difference between pregnant and non-pregnant with CPA, that the pregnant group had more hypermethylated DMPs (67.94% vs 22.16%) and less hypomethylated DMPs (32.93% vs 77.84%). The proportion of hypermethylated DMPs was relatively high on chromosomes 1 (9.68% vs 8.67%) and X (4.99% vs 3.35%) but lower on chromosome 2(7.98% vs 12.92%). In pregnant patients with CPA, 576 hypomethylated DMPs and 1109 hypermethylated DMPs were identified in the DNA promoter region. Bioinformatics analysis indicated that the Wnt/ß-Catenin pathway, Ras/MAPK Pathway and PI3K-AKT Pathway were associated with the development of CPA during pregnancy. CONCLUSIONS: Genome-wide DNA methylation profiling of CPA in non-pregnant and pregnant patients was identified in the present study. Alterations of DNA methylation were associated with the pathogenesis and exacerbation of CPA during pregnancy.


Assuntos
Adenoma Adrenocortical/patologia , Metilação de DNA/genética , Adenoma Adrenocortical/fisiopatologia , Adulto , Metilação de DNA/imunologia , Feminino , Crescimento e Desenvolvimento/genética , Crescimento e Desenvolvimento/fisiologia , Humanos , Gravidez
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