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1.
Gynecol Endocrinol ; : 1-4, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35532201

RESUMO

OBJECTIVE: This study aimed to investigate serum levels of adiponectin, and the mRNA expression of forkhead box C2 (FOXC2) and glucose transporter-4 (GLUT4) in visceral adipose tissue obtained from patients with gestational diabetes mellitus (GDM) and healthy pregnant women. METHODS: Venous blood samples were obtained from 60 pregnant women with gestational normal glucose tolerance (GNGT) and 21 patients with GDM. Visceral adipose tissues were obtained from 11 women with GDM and 30 with GNGT. Serum adiponectin levels were detected by enzyme-linked immunosorbent assay, and FOXC2 and GLUT4 mRNA expression were detected by quantitative polymerase chain reaction. RESULTS: Serum adiponectin concentrations were lower in the women with GDM than in the controls (p < .05). FOXC2 and GLUT4 mRNA expression were decreased in visceral adipose tissue of GDM women than in the controls (p < .05). Correlation analyses showed that FOXC2 tended to have a positive correlation with GLUT4 in GDM patients' visceral adipose tissue (p =.0564). CONCLUSION: Our results revealed that decreased adiponectin, FOXC2, and GLUT4 expression were associated with increased risk of GDM and the regulation mechanism of GLUT4 mediated by FOXC2 would be the focus of further studies.

2.
Cell Death Differ ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534546

RESUMO

The development of chemotherapy resistance is the most vital obstacle to clinical efficacy in gastric cancer (GC). The dysregulation of the Wnt/beta-catenin signaling pathway is critically associated with GC development and chemotherapy resistance. Ferroptosis is a form of regulated cell death, induced by an iron-dependent accumulation of lipid peroxides during chemotherapy. However, whether the Wnt/beta-catenin signaling directly controls resistance to cell death, remains unclear. Here, we show that the activation of the Wnt/beta-catenin signaling attenuates cellular lipid ROS production and subsequently inhibits ferroptosis in GC cells. The beta-catenin/TCF4 transcription complex directly binds to the promoter region of GPX4 and induces its expression, resulting in the suppression of ferroptotic cell death. Concordantly, TCF4 deficiency promotes cisplatin-induced ferroptosis in vitro and in vivo. Thus, we demonstrate that the aberrant activation of the Wnt/beta-catenin signaling confers ferroptosis resistance and suggests a potential therapeutic strategy to enhance chemo-sensitivity for advanced GC patients.

3.
J Clin Epidemiol ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35537604

RESUMO

OBJECTIVE: Nutritional screening tools should be sensitive, simple, and easy to use. Differing opinions among clinicians concern the simplicity of the three tools - the Global Leadership Initiative on Malnutrition (GLIM) criteria, Nutritional Risk Screening 2002 (NRS-2002) and Patient Generated Subjective Global Assessment (PG-SGA). For each tool, we estimate prediction of overall survival (OS) in tumor staging, sensitivity, specificity. NRS-2002 is favored by clinicians because it is simple to use. We compare its sensitivity and specificity with GLIM and PG-SGA STUDY DESIGN AND SETTING: This is an analysis of data from 1358 adult colorectal cancer patients recruited in a multicenter from July 2013 to July 2018. RESULTS: In Kaplan-Meier Models, each tool was found to be significantly predictive of overall survival - NRS-2002 (1.28), GLIM (1.49) and PG-SGA (1.42). Use of any tool improved prediction of survival at tumor staging. NRS-2002 has superior specificity (0.90) to diagnose patients without nutritional deficits (GLIM 0.62, PG-SGA 0.82). CONCLUSION: This study provides evidence for the superiority of NRS-2002 accurately identify colorectal cancer patients without nutritional limitations. Compared with the complexity of the other tools, NRS-2002 is simplest to use in routine nutritional screening. in busy clinical practice.

4.
Methods Enzymol ; 667: 427-453, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35525550

RESUMO

With the increased appreciation of the biological relevance of pseudokinase (PSK) allostery, the broadening of small molecule strategies to target PSK function is of particular importance. We and others have pursued the development of small molecule allosteric modulators of the STRAD pseudokinase by targeting its ATP binding pocket. The purpose of this effort is to modulate the function of the LKB1 tumor suppressor kinase, which exists in a trimer with the STRAD PSK and the adaptor protein MO25. Here we provide detailed guidance regarding the different methods we have used for medium throughput screening to identify STRAD ligands and measure their impact on LKB1 kinase activity. Our experience supports preferential use of direct measurements of LKB1 kinase activity, and demonstrates the limitations of indirect assessment methods in the development trans-acting allosteric modulators.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Regulação Alostérica , Fosforilação
5.
Comput Intell Neurosci ; 2022: 4105942, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463231

RESUMO

Aiming at the problem of low accuracy of traditional algorithm model, an intelligent recognition model of business English translation based on an improved GLR algorithm is proposed. Through this algorithm, the automatic sentence recognition technology is established, and according to the characteristics of business English, the improved GLR algorithm is used for collection, sorting, and analysis, so as to realize the intelligent recognition of business English. The results show that based on the improved GLR algorithm, the recognition accuracy is high, and the comprehensive score is 92.5 points, which overcomes the disadvantages of the GLR algorithm, and the operation speed and processing are improved. Based on the improved GLR algorithm, the intelligent translation of business English is realized, which is accurate and fast, and greatly promotes the learning and development of business English.


Assuntos
Algoritmos , Redes Neurais de Computação , Inteligência , Idioma , Traduções
6.
BMC Cardiovasc Disord ; 22(1): 191, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468725

RESUMO

BACKGROUND: To explore possible associations between glucose transporter 4 (GLUT4) genetic polymorphisms in the patients with coronary heart disease (CHD) in Han and Uygur Chinese populations in Xinjiang, China. METHODS: Two GLUT4 polymorphisms (rs5418 and rs5435) were genotyped in 1262 Han (628 CHD patients and 634 healthy controls) and 896 Uyghur (397 CHD patients and 499 healthy controls) Chinese populations. RESULTS: In the Han Chinese population, there were no significant differences in allelic or genotypic distribution of rs5418 and rs5435 between the CHD and control groups (all P > 0.05). However, in the Uygur population, there were significant differences in genotype and allele distributions for rs5418 between CHD and the control group (all P < 0.05). Binary Logistic regression analysis showed that carriers with the rs5418 A allele had a higher risk of CHD compared to carriers of the rs5418 G allele (OR = 1.33, 95% CI: 1.069-1.649, P = 0.01), after adjustment for gender, age, drinking and smoking behavior, hypertension and diabetes. Furthermore, haploid association analysis of the two SNP loci of the GLUT4 gene showed that the AC haplotype was associated with CHD in the Uygur population (P = 0.001598; OR = 1.36, 95% CI = 1.1228-1.6406). CONCLUSIONS: rs5418 GLUT4 gene variants are associated with CHD in the Uygur Chinese population.


Assuntos
Doença das Coronárias , Polimorfismo de Nucleotídeo Único , /genética , Doença das Coronárias/diagnóstico , Doença das Coronárias/genética , Genótipo , Transportador de Glucose Tipo 4 , Humanos
7.
BMC Cardiovasc Disord ; 22(1): 152, 2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35392816

RESUMO

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) participates in the occurrence and development of cardiovascular and cerebrovascular diseases such as stroke and coronary heart disease by regulating inflammatory reactions, programmed cell death, and other pathological processes. Previous studies revealed that the MALAT1 gene polymorphism was associated with cardiac and cerebrovascular diseases. However, the prognostic role of the MALAT1 polymorphism in major adverse cardiac and cerebrovascular events (MACCEs) remains unknown. Therefore, this study intends to explore the association between the MALAT1 rs3200401 polymorphism and MACCEs. METHOD: We enrolled 617 myocardial infarction (MI) patients and 1125 control participants who attended the First Affiliated Hospital of Xinjiang Medical University from January 2010 to 2018. SNPscan™ typing assays were used to detect the MALAT1 rs3200401 genotype. During the follow-up, MACCEs were recorded. Kaplan-Meier curves and univariate and multivariate Cox survival analyses were used to explore the correlation between MALAT1 gene polymorphisms and the occurrence of MACCEs. RESULTS: Among the total participants and MI patients, the frequencies of the T allele (total Participants 19.5% vs. 15.3%, P = 0.047, MI patients 20.7% vs. 14.1%, P = 0.014) and CT + TT genotypes (total Participants 37.4% vs. 28.1%, P = 0.013, MI patients 39.5% vs. 25.8%, P = 0.003) were significantly higher in subjects with MACCEs than in subjects without MACCEs. However, in control participants, the frequencies of the T allele (16.6% vs. 16.0%, P = 0.860) and CT + TT genotypes (31.4% vs. 29.3%, P = 0.760) were not higher in subjects with MACCEs than in subjects without MACCEs. In addition, among the total participants and MI patients, the Kaplan-Meier curve analysis indicated that the subjects with rs3200401 CT + TT genotypes had a higher incidence of MACCEs than CC genotype carriers (P = 0.015, P = 0.001). Nevertheless, similar results were not observed in the control participants (P = 0.790). Multivariate Cox regression indicated that compared with patients with the CC genotype, patients with CT + TT genotypes had a 1.554-fold increase in MACCE risk (hazard ratio: 1.554, 95% confidence interval: 1.060-2.277, P = 0.024). CONCLUSIONS: The MALAT1 rs3200401 CT + TT genotypes could be a risk factor for MACCEs in MI patients, suggesting that the MALAT1 gene may become a biomarker for poor prognosis in MI patients.


Assuntos
Infarto do Miocárdio , RNA Longo não Codificante , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , RNA Longo não Codificante/genética
8.
Int Immunopharmacol ; 109: 108793, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35483234

RESUMO

Follistatin-related protein 1 (FSTL1) is significantly associated with the asthma severity and outcome in humans and diverse mouse models of asthma. Previous studies have also suggested that FSTL1 could activate autophagy and NLRP3, thus playing as a causative agent in the asthma progression. However, mechanisms that regulate airway epithelial cell-specific FSTL1 expression and function in asthma are unknown. Here, we further evaluated the spatiotemporal relationships between the FSTL1 and asthma development through ovalbumin (OVA) -induced asthma models. Integrative analysis in asthmatics airway epithelium identifies microRNA (miR)-200b-3p as a novel upstream of FSTL1. Next, we collected airway biopsies, induced sputum, and blood samples isolated from asthmatics patients and the OVA-induced mouse model. We revealed that miR-200b-3p expression is downregulated in asthmatics airway epithelium, while its expression was negatively correlated with FSTL1. On this basis, the function and expression pattern analysis of miR-200b-3p were performed using miRNA-target prediction databases and long non-coding RNA (lncRNA) microarray assay. It is illustrated that miR-200b-3p, which is downregulated with pro-fibrotic stimulation of TGF-ß1, could also be sponged by lncRNA PCAT19 and regulate FSTL1 expression in asthma progression. In vivo, miR-200b-3p overexpression in mice prevents OVA-induced airway remodeling and inflammation. Lastly, protective roles of miR-200b-3p are partly attributed to the direct and functional repression of FSTL1. Our findings suggest a crucial role for the miR-200b-3p/FSTL1 axis in regulating asthmatic's airway remodeling and inflammation phenotype.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35358050

RESUMO

The bounded antisynchronization (AS) problem of multiple discrete-time neural networks (NNs) based on the fuzzy model is studied, in consideration of the differences in quantity and communication among different NN groups, the variabilities of dynamics, and communication topological affected by environments. To reduce the energy consumption of communication, a cluster pinning communication mechanism is proposed, and an impulsive observer is designed to estimate the state of target NN. Then, a multilevel hybrid controller based on the impulsive observer is built including the AS controller and the bounded synchronization (BS) controller. Sufficient conditions for bounded AS are obtained by analyzing the stability of the BS augmented error (BSAE) and the AS augmented error (ASAE) based on the fuzzy-based Lyapunov functional (FBLF). Finally, a numerical example and an application example are given to verify the validity of the obtained results.

10.
Bone Res ; 10(1): 29, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35296649

RESUMO

Periodontal ligament stem cells (PDLSCs) are a key cell type for restoring/regenerating lost/damaged periodontal tissues, including alveolar bone, periodontal ligament and root cementum, the latter of which is important for regaining tooth function. However, PDLSCs residing in an inflammatory environment generally exhibit compromised functions, as demonstrated by an impaired ability to differentiate into cementoblasts, which are responsible for regrowing the cementum. This study investigated the role of mitochondrial function and downstream long noncoding RNAs (lncRNAs) in regulating inflammation-induced changes in the cementogenesis of PDLSCs. We found that the inflammatory cytokine-induced impairment of the cementogenesis of PDLSCs was closely correlated with their mitochondrial function, and lncRNA microarray analysis and gain/loss-of-function studies identified GACAT2 as a regulator of the cellular events involved in inflammation-mediated mitochondrial function and cementogenesis. Subsequently, a comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) and parallel reaction monitoring (PRM) assays revealed that GACAT2 could directly bind to pyruvate kinase M1/2 (PKM1/2), a protein correlated with mitochondrial function. Further functional studies demonstrated that GACAT2 overexpression increased the cellular protein expression of PKM1/2, the PKM2 tetramer and phosphorylated PKM2, which led to enhanced pyruvate kinase (PK) activity and increased translocation of PKM2 into mitochondria. We then found that GACAT2 overexpression could reverse the damage to mitochondrial function and cementoblastic differentiation of PDLSCs induced by inflammation and that this effect could be abolished by PKM1/2 knockdown. Our data indicated that by binding to PKM1/2 proteins, the lncRNA GACAT2 plays a critical role in regulating mitochondrial function and cementogenesis in an inflammatory environment.

11.
BMJ Open ; 12(3): e057122, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35232791

RESUMO

INTRODUCTION: Endometrial thickness is an important parameter to evaluate endometrial receptivity. An appropriate endometrial thickness is necessary for both embryo implantation and maintaining normal pregnancy. Women with thin endometrium are one of the critical challenges in the clinic, and current therapeutic strategies for thin endometrium remain suboptimal. The stromal vascular fraction (SVF) derived from adipose tissue contains a variety of cells, mainly adipose-derived stem/stromal cells and adipose cells. Recently, adipose tissue-derived SVF showed tremendous potential for treating thin endometrium due to its capacity to repair and regenerate tissues. The application of SVF in animal models for treating thin endometrium has been investigated. However, limited evidence has demonstrated the efficacy and safety of autologous SVF in patients with thin endometrium. METHODS AND ANALYSIS: This study is a single-centre, longitudinal, prospective self-control study to investigate the preliminary efficacy and safety of autologous SVF in improving the pregnancy outcome of infertile patients with thin endometrium. Thirty patients diagnosed with thin endometrium will be recruited based on the inclusion and exclusion criteria. The SVF suspension will be transferred into the uterine cavity via an embryo transfer catheter. Then, comparisons between pretreatment and post-treatment will be analysed, and the outcomes, including endometrial thickness, menstrual volume and duration, frequency and severity of adverse events and early pregnancy outcomes, will be measured within a 3-month follow-up, while late pregnancy outcomes and their offspring will be followed up via telephone for 2 years. The proportion of patients with improved symptoms will be calculated and compared. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Peking University Third Hospital (reference number: REC2020-165). Written informed consent will be provided for patients before being included. The results will be presented at academic conferences and a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2000035126.


Assuntos
Infertilidade Feminina , Autocontrole , Tecido Adiposo , Animais , Endométrio , Feminino , Humanos , Infertilidade Feminina/terapia , Gravidez , Estudos Prospectivos
12.
Dig Dis Sci ; 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35258755

RESUMO

BACKGROUND: Serum mac-2-binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis assessment in patients with different liver diseases. For chronic hepatitis B infection (CHB), advanced fibrosis or cirrhosis is a risk factor for liver cancer and hepatic decompensation. We aimed to assess the role of serum M2BPGi in prediction of persistence of advanced fibrosis in CHB patients despite potent antiviral therapy. METHODS: CHB patients with advanced fibrosis or cirrhosis who were put on nucleos(t)ide analogs for ≥ 3 years with normal alanine aminotransferase and undetectable serum HBV DNA were prospectively recruited. Assessment of liver fibrosis with transient elastography (TE) and M2BPGi measurements were performed at baseline and repeated at 3 years. Advanced fibrosis and cirrhosis were defined by liver stiffness (LS) ≥ 9.0 kPa and ≥ 12.0 kPa, respectively. RESULTS: A total of 143 patients (M:F = 101:42; median age 58.7 years; 53.8% cirrhotic) were recruited and completed paired assessment. The median value of baseline LS and M2BPGi were 12.0 (IQR: 10.5-18.2) kPa and 0.99 cut-off-index (IQR: 0.75-1.74) (COI), respectively, with 96% concordance for diagnosing F3/F4. Ninety-six (67.1%) patients had persistent advanced fibrosis or cirrhosis at 3 years despite continuation of long-term antiviral treatment. Upon multivariate analysis, baseline M2BPGi (OR 2.128, 95% CI 1.037-4.366) and presence of central obesity (OR 4.648, 95% CI 1.742-12.402) were significantly associated with persistent advanced fibrosis or cirrhosis at 3 years. Baseline M2BPGi ≥ 1.265 COI has 50.6% sensitivity and 79.4% specificity for predicting persistent advanced fibrosis or cirrhosis at 3 years (area under the receiver-operating characteristic curve: 0.695). The presence of central obesity in combination with baseline M2BPGi ≥ 1.265 COI was associated with 95.7% patients having persistent advanced fibrosis or cirrhosis at 3 years. HCC development was observed in five patients during follow-up and was associated with bigger median increase in the level of serum M2BPGi compared to patients without HCC (46% vs 6.2%, P = 0.038). CONCLUSION: Persistent advanced fibrosis or cirrhosis was observed in two-thirds of CHB patients despite potent antiviral therapy. High serum M2BPGi and central obesity were associated with more than twofold and fourfold increase in risk of persistent advanced fibrosis or cirrhosis, respectively.

13.
Gastroenterol Res Pract ; 2022: 7639968, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309108

RESUMO

Objective: To evaluate the Chinese new gastric cancer screening score (i.e., Li's score) and Kyoto Classification of Gastritis for screening gastric cancer. Methods: A total of 702 patients were scored using the two scoring methods. Gastric atrophy, intestinal metaplasia, and gastric cancer (including early gastric cancer) were compared between the two scoring methods. The area under the ROC curve, sensitivity, and specificity of the two scoring methods were evaluated. Results: Both of the two scoring methods found that gastric atrophy, intestinal metaplasia, and gastric cancer (including early gastric cancer) were all significantly higher in the medium-risk and high-risk group patients than those in the low-risk group patients. According to the Kyoto Classification of Gastritis, patients in the high-risk group had more gastric atrophy, intestinal metaplasia, and gastric cancer than those in the medium-risk group patients. Gastric atrophy, intestinal metaplasia, and gastric cancer in the low-risk and medium-risk group patients evaluated by the Li score were all significantly higher than those in patients with corresponding risk level evaluated by Kyoto Classification of Gastritis, respectively. The area under the ROC curve of the Li score was 0.702, and the sensitivity and specificity were 57.6% and 85.3%, respectively. The area under the ROC curve of the Kyoto Classification of Gastritis was 0.826, and the sensitivity and specificity were 75.4% and 83.6%, respectively. Conclusion: Both Li's score and Kyoto Classification of Gastritis showed good screening value for gastric cancer, but Kyoto Classification of Gastritis was more sensitive than the Li score.

14.
Ultrason Sonochem ; 84: 105964, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35231865

RESUMO

This study aimed to investigate influence of ultrasonic treatment on physicochemical and antioxidant properties of mung bean protein hydrolysate (MPH). Physicochemical properties of MPH were evaluated by Tricine-SDS-PAGE, particle size distribution, fourier transform infrared spectroscopy (FTIR) and fluorescence spectroscopy, among others. Radicals scavenging activities of ABTS, hydroxyl, superoxide anion, Fe2+ chelating ability and reducing power characterized antioxidant activities of MPH. MPH contained four bands of 25.6, 12.8, 10.6 and 4.9 kDa, in which 4.9 kDa was the most abundant. Ultrasonic treatment increased the contents of aromatic and hydrophobic amino acids in MPH. Ultrasonic treatment decreased the content of α-helix of MPH and increased ß-sheet and ß-turn compared to MPH. MPH-546 W (ultrasonic treatment 546 W, 20 min) had the lowest average particle size (290.13 nm), zeta potential (-36.37 mV) and surface hydrophobicity (367.95 A.U.). Antioxidant activities of ultrasonicated-MPH increased with the ultrasonic power, achieving the lowest IC50 (mg/mL) of 0.1087 (ABTS), 1.796 (hydroxyl), 1.003 (superoxide anion) and 0.185 (Fe2+ chelating ability) in 546 W power. These results indicated ultrasonic treatment would be a promising method to improve the antioxidant properties of MPH, which would broaden the application scope of MPH as bioactive components in the food industry.


Assuntos
Fabaceae , Vigna , Antioxidantes/química , Antioxidantes/farmacologia , Hidrólise , Hidrolisados de Proteína/química , Vigna/química
15.
Biochem Pharmacol ; 198: 114948, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35192847

RESUMO

Acute myeloid leukemia (AML) is a malignant proliferative disease of myeloid hematopoietic origin and cannot be treated appropriately at present. This is due to the fact that leukemia cells are not sensitive to some of the traditional chemotherapy drugs. Or some chemotherapeutic drugs are too toxic to normal cells, affecting their wide clinical application. In this study, we identified BAM15 as a novel mitochondrial uncoupling agent by screening a library of small molecule compounds that inhibit AML cell activity. BAM15 significantly inhibited proliferation and promoted apoptosis in AML cells while at the same time being less cytotoxic to normal cells. The mechanism may be related to the disturbance of the ROS production balance. In vivo investigations revealed that BAM15 effectively suppressed AML progression and prolonged the survival time of mice. In addition, we found that BAM15 can be used in combination with cytarabine to enhance its anti-cancer activity and inhibit the activity of primary cells in AML. Therefore, we identified BAM15 as a potential drug candidate for the treatment of AML.


Assuntos
Leucemia Mieloide Aguda , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Citarabina/farmacologia , Citarabina/uso terapêutico , Diaminas , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Camundongos , Oxidiazóis , Pirazinas/farmacologia , Espécies Reativas de Oxigênio
16.
Ann Neurol ; 91(5): 704-715, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35152460

RESUMO

OBJECTIVE: CGG/GGC repeat expansion in FMR1 and NOTCH2NLC is reportedly associated with movement disorders; therefore, we hypothesized that the CGG repeat expansion in LRP12, NUTM2B-AS1, and GIPC1, which was previously identified in myopathy, might also be associated with movement-disorder phenotypes. Here, we investigated whether CGG repeat expansion in LRP12, NUTM2B-AS1, and GIPC1 presents in a cohort of patients with movement disorders. METHODS: We screened for the CGG repeat expansion in LRP12, NUTM2B-AS1, and GIPC1 in 1,346 movement-disorder patients and 1,451 matched healthy controls. RESULTS: No patients or controls harbored expanded CGG repeats in LRP12 or NUTM2B-AS1, whereas 16 patients harbored >40 CGG repeats in GIPC1, with 11 of these patients harboring >60 CGG repeats. One control individual harbored an expanded GIPC1 allele (83 CGG units), suggesting that approximately 1% of patients affected by movement disorders in our population might harbor GIPC1 CGG repeat expansion, with this likely extremely rare in healthy controls (<0.001). The clinical phenotypes of the GIPC1 CGG repeat-positive patients strongly resembled those in patients displaying NOTCH2NLC GGC repeat-positive movement disorders. Additionally, the GIPC1 CGG repeat-positive patients presented white-matter hyperintensities but without typical NOTCH2NLC-related high-intensity signals in the corticomedullary junction. Furthermore, 44% of the GIPC1 CGG repeat-positive patients showed a cognitive deficit, and skin biopsies in 2 patients revealed deposition of intranuclear inclusions. INTERPRETATION: The CGG repeat expansion in GIPC1 might be associated with movement-disorder phenotypes and lead to diseases related to intranuclear inclusions. ANN NEUROL 2022;91:704-715.


Assuntos
Transtornos dos Movimentos , Distrofias Musculares , Proteínas Adaptadoras de Transdução de Sinal/genética , Estudos de Coortes , Proteína do X Frágil de Retardo Mental/genética , Humanos , Corpos de Inclusão Intranuclear/patologia , Transtornos dos Movimentos/genética , Distrofias Musculares/genética , Expansão das Repetições de Trinucleotídeos/genética
17.
Int J Mol Sci ; 23(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35162936

RESUMO

Plants are vulnerable to a number of abiotic and biotic stresses that cause a substantial decrease in the production of plants. Plants respond to different environmental stresses by experiencing a series of molecular and physiological changes coordinated by various phytohormones. The use of phytohormones to alleviate stresses has recently achieved increasing interest. Brassinosteroids (BRs) are a group of polyhydroxylated steroidal phytohormones that are required for the development, growth, and productivity of plants. These hormones are involved in regulating the division, elongation, and differentiation of numerous cell types throughout the entire plant life cycle. BR studies have drawn the interest of plant scientists over the last few decades due to their flexible ability to mitigate different environmental stresses. BRs have been shown in numerous studies to have a positive impact on plant responses to various biotic and abiotic stresses. BR receptors detect the BR at the cell surface, triggering a series of phosphorylation events that activate the central transcription factor (TF) Brassinazole-resistant 1 (BZR1), which regulates the transcription of BR-responsive genes in the nucleus. This review discusses the discovery, occurrence, and chemical structure of BRs in plants. Furthermore, their role in the growth and development of plants, and against various stresses, is discussed. Finally, BR signaling in plants is discussed.


Assuntos
Brassinosteroides/metabolismo , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Desenvolvimento Vegetal , Estresse Fisiológico
18.
Front Immunol ; 13: 820164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222395

RESUMO

Objectives: Sepsis is a clinical disease that is typically treated in the intensive care unit, and the complex pathophysiology under this disease has not been thoroughly understood. While ferroptosis is involved in inflammation and infection, its effect in sepsis is still unknown. The study aimed to identify ferroptosis-related genes in sepsis, providing translational potential therapeutic targets. Methods: The dataset GSE65682 was used to download the sample source from the Gene Expression Omnibus (GEO) database. Consensus weighted gene co-expression network analysis (WGCNA) was performed to find suspected modules of sepsis. The differentially expressed genes (DEGs) most significantly associated with mortality were intersected with those altered by lipopolysaccharide (LPS) treatment and were further analyzed for the identification of main pathways of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The related pathway markers were further verified by qPCR. Results: A total of 802 blood samples with sepsis were included for WGCNA, which identified 21 modules. Intersected with ferroptosis databases and LPS treatment groups, we identified two ferroptosis-related genes: PEBP1 and LPIN1. Only LPIN1 contributes to a poor outcome. Then, 205 DEGs were further identified according to the high or low LPIN1 expression. Among them, we constructed a gene regulatory network with several transcriptional factors using the NetworkAnalyst online tool and identified that these genes mostly correlate with inflammation and immune response. The immune infiltration analysis showed that lower expression of LPIN1 was related to macrophage infiltration and could be an independent predictor factor of the survival status in sepsis patients. Meanwhile, the multivariate Cox analysis showed that LPIN1 had a significant correlation with survival that was further verified by in vitro and in vivo experiments. Conclusion: In conclusion, LPIN1 could become a reliable biomarker for patient survival in sepsis, which is associated with immune and inflammation status.


Assuntos
Lipopolissacarídeos , Sepse , Biomarcadores/metabolismo , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Imunidade , Fosfatidato Fosfatase , Sepse/metabolismo
19.
IEEE Trans Cybern ; PP2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34995201

RESUMO

This work is concerned with the anti-synchronization (A-S) of drive-response (D-R) memristive neural networks (MNNs) based on fuzzy rules. A novel impulsive sampled-data communication mechanism is proposed by considering information security of the MNNs, in which the random response delay of sensors caused by the impulse signal is also investigated. As the state of MNNs cannot be outputted accurately and transmitted persistently, the state observers of the D-R MNNs are established, which is beneficial to design the A-S controller. By analyzing the stability of the augmented error system (AES) based on the fuzzy-based Lyapunov-Krasovskii functional (FLKF), sufficient conditions of the A-S between D-R MNNs are derived. An illustrative example is given to verify the effectiveness of the proposed A-S strategies.

20.
Int J Comput Assist Radiol Surg ; 17(4): 731-744, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35032245

RESUMO

PURPOSE: Surgical robots have multiple manipulators with complex mechanisms and need to work in a narrow space in the patient's body. Therefore, for robot-assisted minimally invasive surgery (RMIS), it is very important to develop a reasonable preoperative planning before surgery. METHODS: A preoperative planning method based on the premise of no collision between surgical instruments and endoscope, an evaluation index with visibility, operability and hand-eye coordination was proposed in this paper. To consider the balance relationship of global optimization index, a multi-objective particle swarm optimization (MOPSO) algorithm was adopted. Because the physical characteristics of each patient are different, the method can determine the selectable area of the incision based on the relevant knowledge of anatomy. RESULTS: The simulation taking the cholecystectomy as an example was performed on a minimally invasive surgical robotic system. The analysis result showed that the proposed preoperative planning method based on the MOPSO could provide surgeons with a reasonable and effective preoperative planning. CONCLUSIONS: The proposed preoperative planning method based on the MOPSO is suitable for patients with different physical characteristics, and can provide a guidance for surgeons and effectively reduce the preoperative planning time and improve the safety and efficiency of the operation, especially a novice surgeon who lacks robot-assisted minimally invasive surgery experience.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Algoritmos , Colecistectomia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Robóticos/métodos
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