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1.
J Hum Genet ; 69(5): 197-203, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38374166

RESUMO

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.


Assuntos
Proteína de Capeamento de Actina CapZ , Deficiências do Desenvolvimento , Epilepsia , Heterozigoto , Hipotonia Muscular , Mutação , Pré-Escolar , Feminino , Humanos , Masculino , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Epilepsia/genética , Sequenciamento do Exoma , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Hipotonia Muscular/genética , Hipotonia Muscular/patologia , Fenótipo , Splicing de RNA/genética , Proteína de Capeamento de Actina CapZ/genética
2.
Ergonomics ; : 1-22, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651950

RESUMO

Mental load is a major cause of human-induced accidents. In this study, an explosive impact sensitivity experiment was used to induce mental load. A combination of subjective questionnaires and objective prospective time-distance tests were used to judge whether subjects experienced mental load. Four indicators, namely, ß, γ, mean pupil diameter, and fixation time were selected by statistical analysis and PCA for the construction of a mental load assessment model. The study found that the occipital lobe was the most sensitive to mental load, especially ß and γ bands. Lastly, it was found that subjects showed different degrees of mental load for the same mental load induction task. The results of the study are applicable to the evaluation and monitoring of the mental characteristics of workers and provide a scientific basis for adjusting the mental load of workers over time to reduce the rate of accidents and enhance production efficiency.


Mental load is the main cause of human-induced accidents. This study used an explosive impact sensitivity experiment to induce mental load in subjects. We found that the mean pupil diameter and fixation time, as well as the beta and gamma bands in the occipital lobe were most sensitive to mental load.

3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(8): 986-989, 2023 Aug 10.
Artigo em Zh | MEDLINE | ID: mdl-37532499

RESUMO

OBJECTIVE: To explore the genetic basis for a child with Isolated sulfite oxidase deficiency (ISOD). METHODS: The child and her parents were subjected to targeted capture and next-generation sequencing. Pathogenicity of candidate variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child was found to harbor compound heterozygous variants of the SUOX gene, namely c.1200C>G (p.Tyr400*) and c.1406_1421delCCTGGCAGGTGGCTAA (p.Thr469Serfs*20), which were inherited from her mother and father, respectively. The c.1200C>G was a known pathogenic variant, while the c.1406_1421delCCTGGCAGGTGGCTAA was unreported previously and predicted to be a pathogenic variant (PVS1+PM2_Supporting +PM3) based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION: The compound c.1200C>G and c.1406_1421delCCTGGCAGGTGGCTAA variants of the SUOX gene probably underlay the pathogenesis of ISOD in this child. Above finding has expanded the spectrum of SUOX gene variants and provided molecular evidence for the clinical diagnosis and genetic counseling for this pedigree.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Criança , Feminino , Humanos , Erros Inatos do Metabolismo dos Aminoácidos/genética , Aconselhamento Genético , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Mutação
4.
J Environ Manage ; 317: 115474, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35751273

RESUMO

Nitrogen loss during composting is closely related to NH4+-N conversion, and ammonia-oxidizing bacteria (AOB) are important microorganisms that promote NH4+-N conversion. Since the biological activity of conventional AOB agents used for compost inoculation declines rapidly during the thermophilic phase of composting, new compound inoculants should be developed that are active during that phase. In the current study, the effects of inoculating cattle manure compost with newly isolated AOB (5%, v/w) [thermotolerant AOB X-2 strain (T-AOB-2), mesophilic AOB X-4 strain (M-AOB-4), and AOB X-2 combined with AOB X-4 (MT-AOB-2-4)] on the conversion of nitrogen, compost maturity, and the resident microbial community were studied. During 35 days of composting, compared with the control, AOB inoculation reduced NH3 emissions by 29.98-46.94%, accelerated the conversion of NH4+-N to NO2--N, increased seed germination values by 13.00-25.90%, and increased the abundance of the microbial community at the thermophilic phase (16.38-68.81%). Network analysis revealed that Bacillaceae play a crucial role in the composting process, with the correlation coefficients: 0.83 (p < 0.05) with NH3, 0.64 (p < 0.05) with NH4+-N, and 0.81 (p < 0.05) with NO2--N. In addition, inoculation with MT-AOB-2-4 notably increased the total nitrogen content of compost, prolonged the sanitation stage, and promoted compost maturity. Hence, MT-AOB-2-4 may be used to increase the microbial community abundance and improve the efficiency of cattle manure composting.


Assuntos
Betaproteobacteria , Compostagem , Microbiota , Amônia , Animais , Bactérias , Bovinos , Esterco/microbiologia , Nitrogênio , Dióxido de Nitrogênio , Oxirredução , Solo
5.
Microb Cell Fact ; 20(1): 117, 2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34120587

RESUMO

BACKGROUND: Biodegradation of antibiotics is a promising method for the large-scale removal of antibiotic residues in the environment. However, the enzyme that is involved in the biodegradation process is the key information to be revealed. RESULTS: In this study, the beta-lactamase from Ochrobactrum tritici that mediates the biodegradation of penicillin V was identified and characterized. When searching the proteins of Ochrobactrum tritici, the ß-lactamase (OtLac) was identified. OtLac consists of 347 amino acids, and predicted isoelectric point is 7.0. It is a class C ß-lactamase according to BLAST analysis. The coding gene of OtLac was amplified from the genomic DNA of Ochrobactrum tritici. The OtLac was overexpressed in E. coli BL21 (DE3) and purified with Ni2+ column affinity chromatography. The biodegradation ability of penicillin V by OtLac was identified in an in vitro study and analyzed by HPLC. The optimal temperature for OtLac is 32 â„ƒ and the optimal pH is 7.0. Steady-state kinetics showed that OtLac was highly active against penicillin V with a Km value of 17.86 µM and a kcat value of 25.28 s-1 respectively. CONCLUSIONS: OtLac demonstrated biodegradation activity towards penicillin V potassium, indicating that OtLac is expected to degrade penicillin V in the future.


Assuntos
Ochrobactrum/enzimologia , Ochrobactrum/genética , Penicilinas/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo , Antibacterianos/metabolismo , Biodegradação Ambiental , Catálise , Clonagem Molecular , DNA Bacteriano , Fermentação , Concentração de Íons de Hidrogênio , Cinética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Temperatura
6.
Sensors (Basel) ; 21(21)2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34770546

RESUMO

BACKGROUND: Although hydraulic support can help enterprises in their production activities, it can also cause fatal accidents. METHODS: This study established a composite risk-assessment method for hydraulic support failure in the mining industry. The key basic event of hydraulic support failure was identified based on fault tree analysis and gray relational analysis, and the evolution mechanism of hydraulic support failure was investigated based on chaos theory, a synthetic theory model, and cause-and-effect-layer-of-protection analysis (LOPA). RESULTS: After the basic events of hydraulic support failure are identified based on fault tree analysis, structure importance (SI), probability importance (PI), critical importance (CI), and Fussell-Vesely importance (FVI) can be calculated. In this study, we proposed the Fussell-Vesely-Xu importance (FVXI) to reflect the comprehensive impact of basic event occurrence and nonoccurrence on the occurrence probability of the top event. Gray relational analysis was introduced to determine the integrated importance (II) of basic events and identify the key basic events. According to chaos theory, hydraulic support failure is the result of cross-coupling and infinite amplification of faults in the employee, object, environment, and management subsystems, and the evolutionary process has an obvious butterfly effect and inherent randomness. With the help of the synthetic theory model, we investigated the social and organizational factors that may lead to hydraulic support failure. The key basic event, jack leakage, was analyzed in depth based on cause-and-effect-LOPA, and corresponding independent protection layers (IPLs) were identified to prevent jack leakage. IMPLICATIONS: The implications of these findings with respect to hydraulic support failure can be regarded as the foundation for accident prevention in practice.


Assuntos
Saúde Ocupacional , Acidentes , Probabilidade , Medição de Risco
7.
Carcinogenesis ; 41(1): 8-17, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-31579913

RESUMO

The N6-methyladenosine (m6A) modification plays important regulatory roles in gene expression, cancer occurrence and metastasis. Herein, we aimed to explore the association between genetic variants in m6A modification genes and susceptibility to colorectal cancer. We used logistic regression models to investigate the associations between candidate single-nucleotide polymorphisms (SNPs) in 20 m6A modification genes and colorectal cancer risk. The false discovery rate (FDR) method was used for multiple comparisons. Dual luciferase assays and RNA m6A quantifications were applied to assess transcriptional activity and measure m6A levels, respectively. We found that SND1 rs118049207 was significantly associated with colorectal cancer risk in a Nanjing population (odds ratio (OR) = 1.69, 95% confidence interval (95% CI) = 1.31-2.18, P = 6.51 × 10-6). This finding was further replicated in an independent Beijing population (OR = 1.36, 95% CI = 1.04-1.79, P = 2.41 × 10-2) and in a combined analysis (OR = 1.52, 95% CI = 1.27-1.84, P = 8.75 × 10-6). Stratification and interaction analyses showed that SND1 rs118049207 multiplicatively interacted with the sex and drinking status of the patients to enhance their colorectal cancer risk (P = 1.56 × 10-3 and 1.41 × 10-2, respectively). Furthermore, rs118049207 served as an intronic enhancer on SND1 driven by DMRT3. SND1 mRNA expression was markedly increased in colorectal tumour tissues compared with adjacent normal tissues. The colorimetric m6A quantification strategy revealed that SND1 could alter m6A levels in colorectal cancer cell lines. Our findings indicated that genetic variants in m6A modification genes might be promising predictors of colorectal cancer risk.


Assuntos
Adenosina/análogos & derivados , Neoplasias Colorretais/genética , Endonucleases/genética , Predisposição Genética para Doença , Adenosina/metabolismo , Idoso , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metilação , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Processamento Pós-Transcricional do RNA , RNA Mensageiro/metabolismo
8.
Cell Tissue Res ; 379(2): 291-300, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31463706

RESUMO

Thyroid hormones (THs) are vital for normal reproductive function and dysregulation of TH impairs follicular development. Although the functions of THs on female reproduction are of great interest, the mechanisms still remain unclear. Many studies have shown that NO plays important roles in female reproduction. In the present study, we investigate the effects of TH dysregulation on nitric oxide synthase types (NOS) expression in rats. Propylthiouracil (PTU) and L-thyroxine were administered to rats to induce hypo- and hyperthyroidism, respectively. Ovarian histology was detected by immunohistochemistry (IHC) and protein or mRNA content was analyzed by Western blotting or RT-PCR, respectively. The results showed that NOS1, NOS2 and NOS3 expressions were detected in the oocyte, granulosa cell and theca cell in all follicular stages, which were up-regulated by eCG treatment. NOS1 protein content was increased in both PTU and L-thyroxine treatments. There were no significant differences in NOS2 levels between the treatment and the control group. However, NOS3 was only increased in the hyperthyroid group. These results were consistent with the IHC staining. The present study provides evidence that TH dysregulation alters NOSs profiles, which suggests that NOSs/nitric oxide (NO) is possibly involved in the regulation of female reproduction.


Assuntos
Óxido Nítrico Sintase/metabolismo , Glândula Tireoide/enzimologia , Glândula Tireoide/fisiopatologia , Animais , Gonadotropina Coriônica/farmacologia , Feminino , Cavalos , Hipertireoidismo/enzimologia , Hipotireoidismo/enzimologia , Isoenzimas/metabolismo , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/enzimologia , Ratos Sprague-Dawley , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo
9.
Arch Toxicol ; 94(1): 325-333, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31797002

RESUMO

Circular RNAs (circRNAs) are an intriguing class of regulatory RNAs involved in the tumorigenesis of many cancers, including colorectal cancer. Mechanistically, circRNAs sponge microRNAs (miRNAs) with specific miRNA response elements (MREs) and compete for regulatory target genes downstream. However, the genetic effects of MREs on colorectal cancer susceptibility remain unclear. The MREs of colorectal cancer-associated circRNAs (CRC-circRNAs) and corresponding single nucleotide polymorphisms (SNPs) were identified by the transcriptome of cancer cells and the 1000 Genomes Project. The association between candidate SNPs and colorectal cancer risk was evaluated in a Chinese population (1150 cases and 1342 controls) and two European populations (9023 cases and 386,896 controls) using logistic regression analysis. Among the 197 candidate SNPs within MREs of 186 CRC-circRNAs, rs25497 in circTUBB was significantly associated with colorectal cancer risk in a Chinese population after false discovery rate (FDR) correction [odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.44-2.21, P = 1.42 × 10-7, PFDR = 2.80 × 10-5] and even reached significance in a genome-wide association study (GWAS) under the dominant model (P = 1.28 × 10-8). Similar results were found in the European populations (ORmeta = 1.30, 95% CI = 1.10-1.53). Both stratification and interaction analyses revealed that rs25497 interacting with smoking affected the colorectal cancer risk (Pinteraction = 1.48 × 10-2). Here, we first comprehensively identified genetic variants in MREs of CRC-circRNAs and evaluated their effects on colorectal cancer risk in both Chinese and European populations. These findings provide basis for a comprehensive understanding of colorectal cancer etiology.


Assuntos
Neoplasias Colorretais/genética , RNA Circular/genética , Fumar/genética , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Células HT29 , Humanos , Masculino , MicroRNAs , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Elementos de Resposta , Fumar/efeitos adversos , População Branca/genética
10.
J Cell Mol Med ; 23(3): 2012-2019, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30569605

RESUMO

Single nucleotide polymorphisms (SNPs) within binding sites of microRNAs (miRNAs) could modify cancer susceptibility by changing the binding affinity of miRNAs on their target mRNA 3'-untranslated regions (UTRs). MicroRNA-21 (miR-21) is involved in the development of colorectal cancer. However, the relationship between SNPs within the binding sites of miR-21 and colorectal cancer risk has not been widely investigated. A case-control study including 1147 patients and 1203 controls was performed to evaluate the association of SNPs in miR-21 binding sites and colorectal cancer risk. Dual-luciferase reporter assays and functional assays were performed to evaluate the effects of miR-21. The SNP rs6504593 C allele conferred an increased risk of colorectal cancer compared with the T allele in an additive model (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36, P = 0.011). Dual-luciferase reporter assays demonstrated that the rs6504593 T allele negatively post-transcriptionally regulated IGF2BP1 by altering the binding affinity of miR-21. Additionally, colorectal cancer cells transiently transfected with miR-21 mimics promoted cell proliferation and suppressed apoptosis, whereas inhibition of miR-21 decreased cell growth. These data suggest that the miR-21 binding site SNP rs6504593 in the IGF2BP1 3'-UTR may alter IGF2BP1 expression and contribute to colorectal cancer risk.


Assuntos
Sítios de Ligação/genética , Neoplasias Colorretais/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões 3' não Traduzidas/genética , Alelos , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação da Expressão Gênica/genética , Células HCT116 , Humanos , Masculino , RNA Mensageiro/genética , Risco
11.
Risk Anal ; 39(7): 1634-1646, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30970163

RESUMO

The coal mine production industry is a complex sociotechnical system with interactive relationships among several risk factors. Currently, causation analysis of gas explosion accidents is mainly focused on the aspects of human error and equipment fault, while neglecting the interactive relationships among risk factors. A new method is proposed through risk coupling. First, the meaning of risk coupling of a gas explosion is defined, and types of risk coupling are classified. Next, the coupled relationship and coupled effects among risk factors are explored through combining the interpretative structural modeling (ISM) and the NK model. Twenty-eight representative risk factors and 16 coupled types of risk factors are obtained through analysis of 332 gas explosion accidents in coal mines in China. Through the application of the combined ISM-NK model, an eight-level hierarchical model of risk coupling of a gas explosion accident is established, and the coupled degrees of different types of risk coupling are assessed. The hierarchical model reveals that two of the 28 risk factors, such as state policies, laws, and regulations, are the root risk factors for gas explosions; nine of the 28 risk factors, such as flame from blasting, electric spark, and local gas accumulation, are direct causes of gas explosions; whereas 17 of the risk factors, such as three-violation actions, ventilation system, and safety management, are indirect ones. A quantitative analysis of the NK model shows that the probability of gas explosion increases with the increasing number of risk factors. Compared with subjective risk factors, objective risk factors have a higher probability of causing gas explosion because of risk coupling.

12.
Reprod Fertil Dev ; 30(9): 1225-1233, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29628021

RESUMO

Cytochrome P450 family 19 (CYP19) plays an important role in follicular development, which is regulated by FSH. Although 3,5,3'-tri-iodothyronine (T3) combines with FSH to induce preantral follicle growth and granulosa cell development, the mechanism involved remains unclear. The aim of the present study was to determine the cellular and molecular mechanisms by which thyroid hormone (TH) and FSH regulate CYP19 expression and sterol biosynthesis during preantral follicle growth. Mice were injected subcutaneously (s.c.) with eCG (Equine chorionic gonadotropin). The results showed that eCG increased CYP19 expression in ovarian cells. CYP19 expression in granulosa cells was increased after FSH treatment, and this response was enhanced by T3. Knockdown of CYP19 significantly decreased granulosa cell viability and hormone-stimulated proliferation. In addition, CYP19 knockdown also blocked T3- and FSH-induced oestradiol (E2) synthesis in granulosa cells. Furthermore, activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was required for T3 and FSH regulation of CYP19 expression. In conclusion, the results of the present study indicate that CYP19 is important for T3- and FSH-induced granulosa cell development in the early stages. CYP19 could be a downstream effector of the PI3K/Akt pathway in regulating TH and FSH during follicular development and sterol biosynthesis. The findings suggest that CYP19 is a novel mediator of T3- and FSH-induced follicular development.


Assuntos
Aromatase/metabolismo , Hormônio Foliculoestimulante/farmacologia , Células da Granulosa/efeitos dos fármacos , Tri-Iodotironina/farmacologia , Animais , Aromatase/genética , Gonadotropina Coriônica/farmacologia , Estradiol/biossíntese , Feminino , Técnicas de Silenciamento de Genes , Gonadotropinas Equinas/farmacologia , Células da Granulosa/metabolismo , Camundongos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo
13.
Arch Toxicol ; 92(6): 1991-1999, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29766219

RESUMO

Although studies have investigated the association of genetic variants and the abnormal expression of estrogen-related genes with colorectal cancer risk, the evidence remains inconsistent. We clarified the relationship of genetic variants in estrogen metabolic pathway genes with colorectal cancer risk and survival. A case-control study was performed to assess the association of single-nucleotide polymorphisms (SNPs) in ten candidate genes with colorectal cancer risk in a Chinese population. A logistic regression model and Cox regression model were used to calculate SNP effects on colorectal cancer susceptibility and survival, respectively. Expression quantitative trait loci (eQTL) analysis was conducted using the Genotype-Tissue Expression (GTEx) project dataset. The sequence kernel association test (SKAT) was used to perform gene-set analysis. Colorectal cancer risk and rs3760806 in SULT2B1 were significantly associated in both genders [male: OR = 1.38 (1.15-1.66); female: OR = 1.38 (1.13-1.68)]. Two SNPs in SULT1E1 were related to progression-free survival (PFS) [rs1238574: HR = 1.24 (1.02-1.50), P = 2.79 × 10-2; rs3822172: HR = 1.30 (1.07-1.57), P = 8.44 × 10-3] and overall survival (OS) [rs1238574: HR = 1.51 (1.16-1.97), P = 2.30 × 10-3; rs3822172: HR = 1.53 (1.67-2.00), P = 2.03 × 10-3]. Moreover, rs3760806 was an eQTL for SULT2B1 in colon samples (transverse: P = 3.6 × 10-3; sigmoid: P = 1.0 × 10-3). SULT2B1 expression was significantly higher in colorectal tumor tissues than in normal tissues in the Cancer Genome Atlas (TCGA) database (P < 1.0 × 10-4). Our results indicated that SNPs in estrogen metabolic pathway genes confer colorectal cancer susceptibility and survival.


Assuntos
Povo Asiático/genética , Neoplasias Colorretais/genética , Estrogênios/metabolismo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Sulfotransferases/genética , Estudos de Casos e Controles , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Transdução de Sinais/genética , Análise de Sobrevida
14.
Chin J Physiol ; 61(3): 152-162, 2018 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-29742817

RESUMO

Thyroid hormones (THs) play a critical role in the development of ovarian cells. Although the effects of THs on female reproduction are of great interest, the mechanism remains unclear. We investigated the effects of TH dysregulation on reproductive hormones in rats. Propylthiouracil (PTU) and L-thyroxine were administered to rats to induce hypo- and hyperthyroidism, respectively, and the reproductive hormone profiles were analyzed by radioimmunoassay (RIA). Ovarian histology was evaluated with hematoxylin and eosin (H&E) staining, and gene protein level or mRNA content was analyzed by western blotting or reverse transcription polymerase chain reaction (RT-PCR). The serum levels of gonadotropin releasing hormone (GnRH) and follicle stimulating hormone (FSH) in both rat models were significantly decreased on day 21, although there were no significant changes at earlier time points. There were no significant differences in luteinizing hormone (LH) or progesterone (P4) levels between the treatment and the control groups. Both PTU and L-thyroxine treatments downregulated estradiol (E2) concentrations; however, the serum testosterone (T) level was increased only in hypothyroid rats at day 21. In addition, the expression levels of FSH receptor, cholesterol side-chain cleavage enzyme (P450scc), and steroidogenic acute regulatory protein (StAR) were decreased in both rat models. Moreover, the onset of puberty was significantly delayed in the hypothyroid group. These results provide evidence that TH dysregulation alters reproductive hormone profiles, and that the initiation of the estrous cycle is postponed in hypothyroidism.


Assuntos
Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/sangue , Hipertireoidismo/sangue , Hipotireoidismo/sangue , Glândula Tireoide/fisiopatologia , Animais , Biomarcadores/sangue , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Modelos Animais de Doenças , Ciclo Estral , Feminino , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/fisiopatologia , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/fisiopatologia , Hormônio Luteinizante/sangue , Ovário/metabolismo , Fosfoproteínas/metabolismo , Progesterona/sangue , Propiltiouracila , Ratos Sprague-Dawley , Maturidade Sexual , Testosterona/sangue , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , Tiroxina , Fatores de Tempo
15.
Eur Neurol ; 73(3-4): 179-83, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25614147

RESUMO

AIMS: To assess the language function of children with benign epilepsy with centrotemporal spikes (BECTS), and investigate associated risk factors. METHODS: The language function of 63 children with BECTS and 30 healthy controls was assessed using the language subtest of the Chinese version of the Wechsler Intelligence Scale for Children (C-WISC). Multiple linear regression analysis was applied to assess the risk factors of language dysfunction in children with BECTS. RESULTS: The total score of language test of C-WISC, and the individual scores, were significantly lower in children with BECTS compared with the scores attained by the healthy controls, and were also significantly lower in children with BECTS with onset earlier than 6 years of age compared with those whose disease onset occurred later. There were no significant correlations between language function and treatment, frequency of seizures, lateralization of centrotemporal spikes, or duration of seizures, but there was a positive correlation between language dysfunction and the age at disease onset. CONCLUSION: Children with BECTS have language difficulties, especially those with earlier disease onset. Early age at seizure onset is a risk factor for language dysfunction in children with BECTS.


Assuntos
Epilepsia Rolândica/complicações , Transtornos do Desenvolvimento da Linguagem/etiologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Testes de Linguagem , Modelos Lineares , Masculino , Fatores de Risco , Convulsões/complicações
16.
Medicine (Baltimore) ; 103(7): e37189, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363905

RESUMO

As a novel form of cell death, oxeiptosis is mainly caused by oxidative stress and has been defined to contribute to the cellular death program in cancer. However, the precise involvement of oxeiptosis-related long non-coding RNAs (lncRNAs) within gastric cancer (GC) remains elusive. Thus, our study was aimed to elucidate the pivotal effect of hub oxeiptosis-related lncRNAs on GC by comprehensively analyzing lncRNA and gene expression data obtained from The Cancer Genome Atlas (TCGA) database. Subsequently, we constructed a risk signature (risk-sig) using lncRNAs and further evaluated its prognostic significance. We successfully identified thirteen lncRNAs closely related with oxeiptosis that exhibited significant relevance to the prognosis of GC, forming the foundation of our meticulously constructed risk-sig. Notably, our clinical analyses unveiled a strong correlation between the risk-sig and crucial clinical parameters including overall survival (OS), gender, TNM stage, grade, M stage, and N stage among GC patients. Intriguingly, the diagnostic accuracy of this risk-sig surpassed that of conventional clinicopathological characteristics, underscoring its potential as a highly informative prognostic tool. In-depth mechanistic investigations further illuminated a robust association between this risk-sig and fundamental biological processes such as tumor stemness, immune cell infiltration, and immune subtypes. These findings provide valuable insights into the complex interplay between oxeiptosis-related lncRNAs and the intricate molecular landscape of GC. Ultimately, leveraging the risk scores derived from our comprehensive analysis, we successfully developed a nomogram that enables accurate prediction of GC prognosis. Collectively, our study established a solid foundation for the integration of thirteen hub oxeiptosis-related lncRNAs into a clinically applicable risk-sig, potentially revolutionizing prognostic assessment in GC and facilitating the development of innovative therapeutic strategies.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , RNA Longo não Codificante/genética , Prognóstico , Nomogramas , Morte Celular
17.
Heliyon ; 10(4): e25736, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38370226

RESUMO

Excessive cavity pressure may result in a sand casting explosion, and corresponding measures should be adopted to prevent these consequences. In this study, the pressure variations in the cavity were first investigated based upon on-site testing by taking the resin contents into consideration, and then the evolution characteristics of sand casting explosion accidents were analyzed in depth by system dynamics, chaos theory, and the bow-tie model. When the resin contents are 1.3 wt%, 1.4 wt%, and 1.5 wt%, the pressures of the gas vent increase by 27.0 Pa, 32.8 Pa, and 35.6 Pa, respectively. To reduce the pressure of the cavity, the resin content should be reduced. The evolutionary process of sand casting explosion accidents has a noticeable butterfly effect and randomness, whose occurrence is comprehensively affected by human, object, environment, management and emergency subsystems. The leading causes of sand casting explosion accidents mainly include the extensive gas evolution characteristics of foundry sand, cavity exhaust blockage, and inadequate safety monitoring. The leading consequences of sand casting explosion accidents mainly include casualties, secondary disasters, and social panic. The implications of these findings concerning sand casting explosion accidents can be regarded as the foundation for accident prevention in practice.

18.
Bioresour Technol ; 399: 130589, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490461

RESUMO

The tolerance of Pseudomonas monteilii X1, isolated from pig manure compost, to Cd and Zn, as well as its capacity for biosorption, were investigated. The minimum inhibitory concentrations (MIC) of Cd and Zn for the strain were 550 mg/L and 800 mg/L, respectively. Untargeted metabolomics analysis revealed that organic acids and derivatives, lipids and lipid-like molecules, and organic heterocyclic compounds were the main metabolites. The glyoxylate and dicarboxylate metabolism pathway were significantly enriched under Cd2+ stress. The isothermal adsorption and adsorption kinetics experiments determined that the strain had adsorption capacities of 9.96 mg/g for Cd2+ and 23.4 mg/g for Zn2+. Active groups, such as hydroxyl, carboxyl, and amino groups on the cell surface, were found to participate in metal adsorption. The strain was able to convert Zn2+ into Zn3(PO4)2·4H2O crystal. Overall, this study suggested that Pseudomonas monteilii has potential as a remediation material for heavy metals.


Assuntos
Compostagem , Metais Pesados , Pseudomonas , Suínos , Animais , Cádmio/química , Zinco/química , Esterco , Metais Pesados/análise , Cinética , Compostos Orgânicos , Adsorção
19.
Minerva Pediatr (Torino) ; 75(4): 501-505, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-30299027

RESUMO

BACKGROUND: The aim of this study was to investigate the effect of early diagnosis in children with Green-Barre Syndrome (GBS) via joint detection of biochemical markers and electrophysiological examination. METHODS: A total of 90 children with (GBS collected from the Department of Neurology, Intensive Care Unit (ICU), Rehabilitation Department of Cerebral Palsy of Children's Hospital Affiliated to Zhengzhou University, Department of Pediatrics of First Affiliated Hospital of Zhengzhou University and Henan Province People's Hospital were selected as the research objects. According to their onset time, they were divided into group A (N.=30) hospitalized within 3 days of onset, group B (N.=30) hospitalized from 4 to 7 days of onset, and group C (N.=30) hospitalized after more than 7 days of onset. The titer levels of serum anti-ganglioside immunoglobulin G (IgG) antibodies, the motor nerve conduction velocity (MCV), Hoffmann reflex (H-reflex) condition and serum immunoglobulin in all groups of children were compared. RESULTS: The levels of serum anti-ganglioside IgG antibodies in three groups of children from low to high were group A

Assuntos
Síndrome de Guillain-Barré , Humanos , Criança , Síndrome de Guillain-Barré/diagnóstico , Gangliosídeos , Biomarcadores , Diagnóstico Precoce , Imunoglobulina G
20.
Cancer Res ; 83(13): 2142-2154, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37115853

RESUMO

Genetic variants in regions encoding 3' untranslated regions (UTR) of mRNA potentially alter miRNA binding affinity and N6-methyladenosine (m6A) levels to affect gene expression. A better understanding of the association of these variants with colorectal cancer susceptibility could facilitate development of cancer prevention and treatment approaches. Here, we analyzed miRNA expression profiles and integrated genetic analyses from 8,533 individuals to evaluate the effects of altered miRNA-binding sites on colorectal cancer risk. The single-nucleotide polymorphism rs11245997 in the BET1L 3'UTR was significantly associated with colorectal cancer risk. The rs11245997 A allele facilitated BET1L expression by disrupting miR-140-3p binding. It also reduced BET1L m6A modification, which upregulated BET1L expression levels through a mechanism mediated by the m6A methyltransferases (METTL14 and WTAP) and the m6A demethylase ALKBH5. Moreover, higher expression of BET1L was associated with advanced tumor stages and poor patient prognosis. Increased BET1L expression promoted growth of colorectal cancer cells in vitro and in vivo, which could be partially rescued with miR-140-3p overexpression. RNA sequencing and pathway analyses indicated that BET1L is associated with the steroid biosynthesis pathway through regulation of HSD17B7, CYP27B1, and COMT. These findings provide insights into the involvement of genetic variants of BET1L in the development and progression of colorectal cancer. SIGNIFICANCE: The integration of miRNA expression profiles and genetic variants identified rs11245997 as a colorectal cancer risk-related variant that reduces miR-140-3p binding and m6A modification, leading to BET1L upregulation to promote colorectal tumorigenesis.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Metiltransferases/metabolismo , MicroRNAs/genética , Carcinogênese , Transformação Celular Neoplásica , Comunicação Celular , Neoplasias Colorretais/genética , Proteínas Qc-SNARE
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