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1.
Neural Regen Res ; 20(3): 821-835, 2025 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38886955

RESUMO

JOURNAL/nrgr/04.03/01300535-202503000-00027/figure1/v/2024-06-17T092413Z/r/image-tiff Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/ß-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury-induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

2.
Commun Biol ; 7(1): 1233, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354127

RESUMO

Overgrowth of Gardnerella vaginalis causes an imbalance in vaginal microecology. The pathogenicity of G. vaginalis is directly regulated by the cAMP receptor protein (CRP). In this study, we resolve the crystal structure of CRPGv at a resolution of 2.22 Å and find some significant differences from homologous proteins. The first 23 amino acids of CRPGv are inserted into the ligand binding pocket, creating a strong steric barrier to ligand entry that has not been seen previously in its homologues. In the absence of ligands, the two α helices used by CRPGv to bind oligonucleotide chains are exposed and can specifically bind TGTGA-N6-TCACA sequences. cAMP and other ligands of CRP homologs are not cofactors of CRPGv. There is no coding gene of the adenylate cyclase, and cAMP could not be identified in G. vaginalis by liquid chromatography tandem mass spectrometry. We speculate that CRPGv may achieve fine regulation through a conformational transformation different from that of its homologous proteins, and this conformational transformation is no longer dependent on small molecules, but may be aided by accessory proteins. CRPGv is the first discovered CRP that is not ligand-regulated, and its active conformation provides a structural basis for drug screening.


Assuntos
Gardnerella vaginalis , Ligantes , Gardnerella vaginalis/genética , Gardnerella vaginalis/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , AMP Cíclico/metabolismo , Proteína Receptora de AMP Cíclico/metabolismo , Proteína Receptora de AMP Cíclico/genética , Proteína Receptora de AMP Cíclico/química , Cristalografia por Raios X , Sítios de Ligação , Modelos Moleculares , Sequência de Aminoácidos , Ligação Proteica , Conformação Proteica
4.
Int Immunopharmacol ; 142(Pt A): 113075, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260312

RESUMO

Medulloblastoma (MB) is the most common malignant brain tumor in children. Within MB, tumors driven by the Sonic Hedgehog (SHH) pathway represent the most heterogeneous subtype, known as SHH subtype medulloblastoma (SHH-MB). Tenovin-6, a recognized p53 activator, has been demonstrated to inhibit autophagy and modulate sirtuin activity, underscoring its potential as a novel therapeutic agent across various malignancies. However, its efficacy in treating SHH-MB remains unexplored. This study aims to investigate the inhibitory effects of tenovin-6 on SHH-MB and elucidate its underlying signaling pathways. We assessed the impact of tenovin-6 on cell proliferation through the CCK-8 and colony formation assays. The scratch and transwell invasion assays were utilized to evaluate the drug's effects on metastasis. Apoptosis and reactive oxygen species (ROS) levels were measured using flow cytometry. Potential signaling pathways were identified via transcriptomics and quantitative PCR (qPCR). Our in vivo studies involved a mouse xenograft model to explore tenovin-6's anticancer efficacy against SHH-MB. The findings indicate that tenovin-6 not only inhibits cell proliferation and metastasis in SHH-MB cell lines but also promotes apoptosis, which is closely linked to its proliferation-inhibiting properties. Additionally, animal experiments confirmed that tenovin-6 suppresses MB growth in vivo. We discovered that tenovin-6 reduces intracellular ROS levels and inhibits autophagy in SHH-MB by disrupting the fusion of autophagosomes with lysosomes, likely through inducing autophagosome formation.

5.
Theranostics ; 14(12): 4683-4700, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239525

RESUMO

N6-methyladenosine (m6A) is the most abundant post-transcriptional dynamic RNA modification process in eukaryotes, extensively implicated in cellular growth, embryonic development and immune homeostasis. One of the most profound biological functions of m6A is to regulate RNA metabolism, thereby determining the fate of RNA. Notably, the regulation of m6A-mediated organized RNA metabolism critically relies on the assembly of membraneless organelles (MLOs) in both the nucleus and cytoplasm, such as nuclear speckles, stress granules and processing bodies. In addition, m6A-associated MLOs exert a pivotal role in governing diverse RNA metabolic processes encompassing transcription, splicing, transport, decay and translation. However, emerging evidence suggests that dysregulated m6A levels contribute to the formation of pathological condensates in a range of human diseases, including tumorigenesis, reproductive diseases, neurological diseases and respiratory diseases. To date, the molecular mechanism by which m6A regulates the aggregation of biomolecular condensates associated with RNA metabolism is unclear. In this review, we comprehensively summarize the updated biochemical processes of m6A-associated MLOs, particularly focusing on their impact on RNA metabolism and their pivotal role in disease development and related biological mechanisms. Furthermore, we propose that m6A-associated MLOs could serve as predictive markers for disease progression and potential drug targets in the future.


Assuntos
Adenosina , RNA , Humanos , Adenosina/metabolismo , Adenosina/análogos & derivados , RNA/metabolismo , Organelas/metabolismo , Animais , Processamento Pós-Transcricional do RNA , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Núcleo Celular/metabolismo , Citoplasma/metabolismo
6.
J Hazard Mater ; 480: 135926, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307018

RESUMO

Cadmium (Cd) pollution poses a significant ecological risk to mangrove ecosystems. Trehalose has excellent potential to mitigate the adverse effects of heavy metals. Unfortunately, the mechanisms related to trehalose-mediated heavy metal tolerance in plants remain elusive. In the present study, we firstly found that Cd induced the accumulation of trehalose and the differential expression of trehalose biosynthesis genes in the roots of mangrove plant Avicennia marina. Then, we found that the application of exogenous trehalose could alleviate the negative effects of Cd on A. marina by phenotypic observation. In addition, photosynthetic parameters and cellular ultrastructure analyses demonstrated that exogenous trehalose could improve the photosynthesis and stabilize the chloroplast and nuclear structure of the leaves of A. marina. Besides, exogenous trehalose could inhibit the Cd2+ influx from the root to reduce the Cd2+ content in A. marina. Subsequently, substrate sensitivity assay combined with ion uptake analysis using yeast cells showed that several trehalose biosynthesis genes may have a regulatory function for Cd2+ transport. Finally, we further identified a positive regulatory factor, AmTPS6, which enhances the Cd tolerance in transgenic Arabidopsis thaliana. Taken together, these findings provide new understanding to the mechanism of Cd tolerance in mangrove A. marina at trehalose aspect and a theoretical basis for the conservation of mangroves in coastal wetlands.

7.
Sci Data ; 11(1): 1003, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39294155

RESUMO

Cotton thrip, Thrips tabaci is a major polyphagous pest widely distributed on a variety of crops around the world, causing huge economic losses to agricultural production. Due to its biological and genomic characteristics, this pest can reproduce quickly and develop resistance to various pesticides in a very short time. However, the lack of high-quality reference genomes has hindered deeper gene function exploration and slows down the development of new management strategies. Here, we assembled a high-quality genome of T. tabaci at the chromosome level for the first time by using Illumina, PacBio long reads, and Hi-C technologies. The 329.59 Mb genome was obtained from 320 contigs, with a contig N50 of 1.53 Mb, and 94.21% of the assembly was anchored to 18 chromosomes. In total, 17,816 protein-coding genes were annotated, and 96.78% of BUSCO genes were fully represented. In conclusion, this high-quality genome provides a valuable genetic basis for our understanding of the biology of T. tabaci and contributes to the development of management strategies for cotton thrip.


Assuntos
Genoma de Inseto , Tisanópteros , Animais , Tisanópteros/genética , Gossypium/genética , Gossypium/parasitologia , Cromossomos de Insetos/genética
8.
BMC Microbiol ; 24(1): 356, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300361

RESUMO

BACKGROUND: Maple is an important ornamental plant in China. With the increasing use of maple trees in landscaping, a symptom of shoot dieback has been observed in Henan province, China. RESULTS: In this study, 28 Diaporthe isolates were obtained from symptomatic shoots of maple trees between 2020 and 2023. Phylogenetic analyses based on five loci (ITS, TEF, CAL, HIS and TUB) coupled with morphology of 12 representative isolates identified three known species (D. eres, D. pescicola and D. spinosa) and one new species, namely D. pseudoacerina sp. nov. Koch's postulates confirmed that all these species were pathogenic. Additionally, D. pseudoacerina was able to infect China wingnut (Pterocarya stenoptera), pear (Pyrus sp.), and black locust (Robinia pseudoacacia). This study marks the first report of Diaporthe spinosa and D. pescicola pathogens infecting maple trees. CONCLUSIONS: These findings enhance the existing knowledge of the taxonomy and host diversity of Diaporthe species as, while also providing valuable information for managing of maple shoot dieback in Henan Province, China.


Assuntos
Acer , Ascomicetos , Filogenia , Doenças das Plantas , Brotos de Planta , Acer/microbiologia , China , Doenças das Plantas/microbiologia , Brotos de Planta/microbiologia , Ascomicetos/genética , Ascomicetos/classificação , Ascomicetos/isolamento & purificação , Ascomicetos/fisiologia , DNA Fúngico/genética , Análise de Sequência de DNA , Pyrus/microbiologia
9.
Cancer Cell Int ; 24(1): 321, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300449

RESUMO

PURPOSE: The aim of this study is to delve into the value of N6-Methyladenosine (m6A)-associated genes (MAGs) in pancreatic cancer (PC) prognosis. METHODS: PC sequencing data and corresponding clinicopathological information were retrieved from GEO and TCGA databases. We filtered 19 MAGs in PC specimens and implemented functional annotation in biology. Later, the m6A modification pattern was stratified into m6Acluster A-B according to MAG expression levels, and further categorized into genecluster A-C based on differentially expressed genes between m6Acluster A and B. Next, a MAG-based prognostic prediction model was established by the least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis. At last, the role of KRT7 in PC were explored. RESULTS: We found m6Acluster A pattern presented enrichment pathways associated with cell apoptosis, proliferation, migration, and cancer pathways. Additionally, high-risk group displayed more dismal prognosis and a higher programmed death-ligand 1 expression. The survival prediction ability of the model was verified in three independent PC GEO datasets. KRT7 is the most momentous risk gene in the established prognostic model. Among 18 clinical samples, the KRT7 protein in the surviving patient samples is lower than that in the deceased patient samples. We also identified elevated expression of KRT7 in PC tumor tissues compared to normal tissues using GEPIA 2. Then, the metastasis of PC cells was promoted by overexpressed KRT7 in vitro and in vivo. And IGF2BP3 upregulated KRT7 by increasing the mRNA stability of KRT7. CONCLUSIONS: The PPM built based on CXCL5, LY6K and KRT7 is an encouraging biomarker to define the prognosis. Additionally, IGF2BP3 promoted KRT7 by stabilizing mRNA of KRT7. And KRT7 promoted the metastasis of PC cells by promoting EMT.

10.
Sensors (Basel) ; 24(17)2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39275717

RESUMO

To detect damage in mechanical structures, acoustic emission (AE) inspection is considered as a powerful tool. Generally, the classical acoustic emission detection method uses a sparse sensor array to identify damage and its location. It often depends on a pre-defined wave velocity and it is difficult to yield a high localization accuracy for complicated structures using this method. In this paper, the passive guided wave phased array method, a dense sensor array method, is studied, aiming to obtain better AE localization accuracy in aluminum thin plates. Specifically, the proposed method uses a cross-shaped phased array enhanced with four additional far-end sensors for AE source localization. The proposed two-step method first calculates the real-time velocity and the polar angle of the AE source using the phased array algorithm, and then solves the location of the AE source with the additional far-end sensor. Both numerical and physical experiments on an aluminum flat panel are carried out to validate the proposed method. It is found that using the cross-shaped guided wave phased array method with enhanced far-end sensors can localize the coordinates of the AE source accurately without knowing the wave velocity in advance. The proposed method is also extended to a stiffened thin-walled structure with high localization accuracy, which validates its AE source localization ability for complicated structures. Finally, the influences of cross-shaped phased array element number and the time window length on the proposed method are discussed in detail.

11.
Biomark Res ; 12(1): 113, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334513

RESUMO

Novel neoadjuvant immunotherapy combined with chemotherapy (neoICT) has improved outcomes for patients with esophageal squamous-cell carcinoma (ESCC), but challenges persist in low response rates and therapy resistance. Little is known about the intra-tumoral heterogeneity in the ESCC tumor microenvironment (TME) that underlies differential responses to neoadjuvant therapy. We applied single-cell RNA sequencing (scRNA-seq) profiling and multiplexed immunofluorescence staining to thoroughly decipher the TME in ESCC specimens from a neoadjuvant anti-PD1 combination therapy clinical trial. The cancer-associated fibroblasts (CAFs) population showed the significant alteration in abundance following neoadjuvant therapy. Specifically, IL6 + CCL2 + immunomodulatory CAFs and a novel CD248 + mechanoresponsive CAFs subset exhibited increasing infiltration. Mechanistically, CD248 + mechanoresponsive CAFs approached and lined the tumor nest to physically block the infiltration of CD8 + T cells and drug delivery, while IL6 + CCL2 + immunomodulatory CAFs induced therapeutic resistance with distinct IL-6 expression. Among patients treated with neoICT, we observed prominent CAF-T cell interactions. In particular, the NECTIN2-TIGIT ligand-receptor pair was enriched in treated samples, and TIGIT was identified as the major inhibitory checkpoint of T cells. Our findings demonstrate distinct alterations in TME constituent responses to neoadjuvant immunotherapy and identify functional phenotypes of CAFs associated with unfavorable therapeutic responses in patients. This provides potential targets to enhance responses to neoadjuvant therapy in ESCC.

12.
JACS Au ; 4(9): 3668-3678, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39328760

RESUMO

Hydrophilic actinide masking agents are believed to be efficient alternatives to circumvent the extensive hazardous organic solvents/diluents typically employed in the liquid-liquid extraction for nuclear waste management. However, the practical application of hydrophilic ligands faces significant challenges in both synthetic/purification procedures and, more importantly, the acid resistance of the ligands themselves. Herein, we have demonstrated the combination of phenanthroline diimide framework with a biomotif of histidine flanking parts could achieve efficient separation of trivalent lanthanides/actinides (also actinides/actinides) under high acidity of over 1 M HNO3. This approach leverages the soft-hard coordination properties of N, O-hybrid ligands, as well as the energetically favored imides for metal coordination and the multiple protonation of histidine. These factors collectively contribute to the synthesis of an easily accessible, highly water-soluble, superior selective, and acid-resistant Am(III) masking agent. Thus, we have shown in this paper, by proper combination of synthetic N, O-hybrid ligand with amino acid, trivalent lanthanide and actinide separation could be efficiently fulfilled in a more sustainable manner.

13.
Microorganisms ; 12(9)2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39338438

RESUMO

With the development of commercialized planting of genetically modified crops, their ecological security risks remain a key topic of public concern. Insect-resistant genetically modified maize, Ruifeng125, which expresses a fusion Bt protein (Cry1Ab-Cry2Aj), has obtained the application safety certificate issued by the Chinese government. To determine the effects of Ruifeng125 on the diversity and dynamics of bacterial communities, the accumulation and degradation pattern of the fusion Bt protein in the rhizosphere soil of transgenic maize were detected. Results showed that the contents of Bt protein varied significantly at different developmental stages, but after straw was returned to the field, over 97% of Bt proteins were degraded quickly at the early stages (≤10 d) and then they were degraded at a relatively slow rate. In addition, the variations in bacterial community diversity in the rhizosphere soil were detected by 16S ribosomal RNA (Rrna) high-throughput sequencing technology. A total of 44 phyla, 435 families, and 842 genera were obtained by 16S rRNA sequencing, among which Proteobacteria, Actinobacia, Acidobacter Acidobacterium, and Chloroflexi were the dominant taxa. At the same developmental stage, no significant differences in soil bacterial diversity were detected between Ruifeng125 and its non-transgenic control variety. Further analysis revealed that developmental stage, rather than the transgenic event, made the greatest contribution to the changes in soil microbial diversity. This research provides important information for evaluating the impacts of Bt crops on the soil microbiome and establishes a theoretical foundation for their environmental safety assessment.

14.
Molecules ; 29(18)2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39339384

RESUMO

A bioactivity-guided separation strategy was used to identify novel antistroke compounds from Gymnadenia conopsea (L.) R. Br., a medicinal plant. As a result, 4 undescribed compounds (1-2, 13, and 17) and 13 known compounds, including 1 new natural product (3), were isolated from G. conopsea. The structures of these compounds were elucidated through comprehensive spectroscopic techniques, such as 1D/2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), and quantum chemical calculations. An oxygen-glucose deprivation/reoxygenation (OGD/R)-injured rat pheochromocytoma (PC12) cell model was used to evaluate the antistroke effects of the isolates. Compounds 1-2, 10-11, 13-15, and 17 provided varying degrees of protection against OGD/R injury in the PC12 cells at concentrations of 12.5, 25, and 50 µM. Among the tested compounds, compound 17 demonstrated the most potent neuroprotective effect, which was equivalent to that of the positive control drug (edaravone). Then, transcriptomic and bioinformatics analyses were conducted to reveal the regulatory effect of compound 17 on gene expression. In addition, quantitative real-time PCR (qPCR) was performed to verify the results of the transcriptomic and bioinformatics analyses. These results suggest that the in vitro antistroke effect of compound 17 may be associated with the regulation of the Col27a1 gene. Thus, compound 17 is a promising candidate for the development of novel antistroke drugs derived from natural products, and this topic should be further studied.


Assuntos
Fármacos Neuroprotetores , Animais , Ratos , Células PC12 , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Acidente Vascular Cerebral/tratamento farmacológico , Orchidaceae/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Estrutura Molecular , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação
15.
Mol Plant Pathol ; 25(9): e70006, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39267531

RESUMO

The pathogen Agrobacterium tumefaciens is known for causing crown gall tumours in plants. However, it has also been harnessed as a valuable tool for plant genetic transformation. Apart from the T-DNA, Agrobacterium also delivers at least five virulence proteins into the host plant cells, which are required for an efficient infection. One of these virulence proteins is VirD5. F-box proteins, encoded in the host plant genome or the Ti plasmid, and the ubiquitin/26S proteasome system (UPS) also play an important role in facilitating Agrobacterium infection. Our study identified two Arabidopsis F-box proteins, D5BF1 and D5BF2, that bind VirD5 and facilitate its degradation via the UPS. Additionally, we found that Agrobacterium partially suppresses the expression of D5BF1 and D5BF2. Lastly, stable transformation and tumorigenesis efficiency assays revealed that D5BF1 and D5BF2 negatively regulate the Agrobacterium infection process, showing that the plant F-box proteins and UPS play a role in defending against Agrobacterium infection.


Assuntos
Agrobacterium tumefaciens , Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Transformação Genética , Arabidopsis/microbiologia , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Agrobacterium tumefaciens/genética , Agrobacterium tumefaciens/patogenicidade , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Carcinogênese/genética , Tumores de Planta/microbiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Regulação da Expressão Gênica de Plantas
16.
J Phys Chem Lett ; 15(38): 9601-9619, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39270134

RESUMO

The all-atomic full-dimensional-level simulations of nonadiabatic molecular dynamics (NAMD) in large realistic systems has received high research interest in recent years. However, such NAMD simulations normally generate an enormous amount of time-dependent high-dimensional data, leading to a significant challenge in result analyses. Based on unsupervised machine learning (ML) methods, considerable efforts were devoted to developing novel and easy-to-use analysis tools for the identification of photoinduced reaction channels and the comprehensive understanding of complicated molecular motions in NAMD simulations. Here, we tried to survey recent advances in this field, particularly to focus on how to use unsupervised ML methods to analyze the trajectory-based NAMD simulation results. Our purpose is to offer a comprehensive discussion on several essential components of this analysis protocol, including the selection of ML methods, the construction of molecular descriptors, the establishment of analytical frameworks, their advantages and limitations, and persistent challenges.

17.
Skin Res Technol ; 30(9): e70042, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39233331

RESUMO

BACKGROUND: Value analysis of a small-molecule fluorescent probe for methylation detection in different cervical lesions. MATERIALS AND METHODS: (1) The grayscale values of distinct lesion tissues were remarkably distinct among the four groups (p < 0.05). The comparison of the grayscale value between the two groups showed that the CA group noticeably exceeded the LSIL and cervicitis groups, and the HSIL group was apparently higher than the LSIL and cervicitis groups (p < 0.05); (2) The mean grayscale values of the enrolled subjects were calculated with 55.21 as the midline, with >55.21 as positive and ≤55.21 as negative. RESULTS: The results showed that the positive rate of the cervicitis group was 0.00%, the LSIL group 67.74%, the HSIL group 83.33%, and the CA group 100.00%. The results among the four groups were notably distinct (p < 0.05); (3) The comparison among DAPI, probe, bright, and merged images of cervicitis, LSIL, HSIL, and CA indicated that different cervical lesions were with quite various stains. CONCLUSION: The grayscale value, positive rate, and stained picture of distinct cervical lesions were remarkably different. The small-molecule fluorescent probe has a good value in differentiating cervical lesions and can be considered for popularization and application.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , Corantes Fluorescentes , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Adulto , Pessoa de Meia-Idade , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Idoso , Sensibilidade e Especificidade , Cervicite Uterina/metabolismo , Displasia do Colo do Útero/diagnóstico
18.
Endokrynol Pol ; 75(4): 438-447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39279313

RESUMO

INTRODUCTION: The purpose of this study was to analyse the correlation between zinc finger antisense 1 (ZFAS1) and obesity and the diagnostic value of obesity complicated with metabolic syndrome (obesity-MS). MATERIAL AND METHODS: Serum levels of ZFAS1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in healthy children, children with simple obesity, and children with obesity-MS. The diagnostic accuracy of ZFAS1 was evaluated using the receiver operator characteristic (ROC) curve. Pearson's method was used to study the correlation between ZFAS1 and other indicators. Logistic regression was used to analyse the significance of ZFAS1 in the progression of obesity to obesity-MS. StarBase V2.0 was used to predict the target gene of ZFAS1 (miR-193a-3p). Bioinformatics methods were used to identify the molecular functions and possible enrichment signalling pathways of downstream target genes of miR-193a-3p. RESULTS: The expression of ZFAS1 in patients with obesity and obesity-MS showed a gradual upward trend, while the expression of miR-193a-3p was the opposite. ZFAS1 could identify obesity-MS children from children with obesity (area under the curve [AUC] = 0.880). ZFAS1 was significantly correlated with body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), and other indicators, while ZFAS1 was an independent influencing factor for the development of obesity into obesity-MS. Furthermore, a total of 104 downstream target genes of miR-193a-3p were identified, which participated in many biological processes such as protein phosphatase regulation, activation of transcription factor activity, and enrichment in MAPK signalling pathway. CONCLUSION: ZFAS1 is dysregulated in obesity and obesity-MS. Abnormal expression of ZFAS1 has high diagnostic value for obesity-MS, and it has the potential to become a clinical diagnostic biomarker for obesity-MS.


Assuntos
Síndrome Metabólica , Obesidade Infantil , RNA Longo não Codificante , Humanos , Síndrome Metabólica/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/sangue , Criança , Masculino , Feminino , Obesidade Infantil/genética , Valor Preditivo dos Testes , Adolescente
19.
JTO Clin Res Rep ; 5(9): 100704, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39282661

RESUMO

Introduction: Transformation to SCLC is a resistance mechanism to tyrosine kinase inhibitor in EGFR-mutated lung adenocarcinoma (LUAD). Nevertheless, the clinical and molecular features of SCLC transformation in LUAD with leptomeningeal metastases (LM) are scarce. Methods: We retrospectively collected 237 patients with NSCLC who underwent lumbar puncture owing to suggestion of LM. All SCLC transformation in cerebrospinal fluid (CSF) was confirmed by two experienced pathologists using cytologic evaluation. CSF circulating tumor DNA (ctDNA) was tested by next-generation sequencing. Results: Tumor cells in CSF samples were found in 111 patients (111 of 237, 46.8%), and eight cases (eight of 111, 7.2%) were identified as having SCLC cells in CSF. Seven patients carried the EGFR mutation, including four patients with EGFR exon 19 deletion and three patients with EGFR exon 21 L858R mutation. Another patient harbored ERBB2 insertion. Seven of these patients were resistant to targeted therapy. CSF ctDNA analysis reported that TP53 and RB1 mutations were common. The median time from the diagnosis of advanced NSCLC to SCLC transformation found in CSF was 9.7 months (95% confidence interval [CI]: 4.0-17.5 mo). The median overall survival since the initial diagnosis of metastatic NSCLC was 15.3 months (95% CI: 1.2-29.4 mo). The median overall survival after SCLC transformation detected in CSF was 5.0 months (95% CI: 4.0-5.9 mo). Conclusions: SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.

20.
World Neurosurg ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299437

RESUMO

OBJECTIVE: To analyze the complications and long-term follow-up results of endovascular treatment for ruptured intracranial posterior circulation aneurysms and identify outcome predictors. METHODS: A total of 194 patients with ruptured intracranial posterior circulation aneurysms treated at our center between January 2014 and June 2023 were included in this retrospective analysis. Factors influencing complications during hospitalization and clinical and angiographic outcomes were analyzed. RESULTS: Complications occurred in 57 patients (29.4%) during hospitalization. The median clinical follow-up time was 46.5 (IQR 26.0-65.3) months, with favorable outcomes observed in 81.4% (158/194) and unfavorable outcomes in 18.5% (36/194) of cases, resulting in an overall mortality rate of 11.9% (23/194). The overall 1-year and 5-year complication-free survival rates were 76.4% and 70.7%, respectively. The overall 1-year and 5-year overall survival rates were 89.5% and 85.4%, respectively. Multifactorial analysis revealed that involvement of the basilar artery (p=0.032) and perioperative external ventricular drainage (p<0.001) were independent risk factors for complications during hospitalization, while advanced age (p=0.030), poor WFNS grade (p=0.003), and use of closed cell design laser cut stents (p=0.041) were independent risk factors for unfavorable outcomes during follow-up. Among the survivors, angiography follow-up was available for 139 patients, with a follow-up rate of 81.2% (139/171) and a median follow-up time of 8 months (IQR 6-12). During this period, 9 patients experienced aneurysm recanalization, and the complete occlusion rate was 85.6%. CONCLUSION: Endovascular treatment is feasible and effective for treating ruptured intracranial aneurysms; however, there are still risks of complications and unfavorable clinical outcomes. The involvement of the BA trunk increases the risk of complications, and the use of closed cell design laser cut stents is associated with unfavorable outcomes. Clinicians should be cautious to avoid the risk factors when treating ruptured posterior circulation aneurysms and strive to minimize the occurrence of complications and unfavorable clinical outcomes.

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