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OBJECTIVE: Glymphatic system is a recently discovered macroscopic waste clearance system associated with numerous neurological diseases. However, little is known about glymphatic system development in neonates. We sought to evaluate diffusion along the perivascular space (ALPS) index, a proxy for glymphatic system function, in neonates and investigate its potential associations with maturation, sex, and preterm birth. METHODS: Diffusion magnetic resonance imaging (MRI) data in 418 neonates, including 92 preterm neonates (57 males) and 326 term neonates (175 males), from the Developing Human Connectome Project were used for evaluating ALPS index. Linear regression modeling was performed to assess group differences in the ALPS index according to preterm birth and sex. Pearson's and partial correlation analysis were performed to assess the association between the ALPS index and gestational age (GA) as well as postmenstrual age (PMA) at MRI. Moderation analysis was performed to assess the moderation effect of preterm birth on the relationship between the ALPS index and PMA. RESULTS: Compared to term neonates, preterm neonates exhibited lower ALPS indices (p < 0.001). The ALPS index positively correlated with PMA (p = 0.004) and GA (p < 0.001). Preterm birth (p = 0.013) had a significant moderation effect on the relationship between the ALPS index and PMA. Sex had no significant direct effect (p = 0.639) or moderation effect (p = 0.333) on ALPS index. INTERPRETATION: Glymphatic system development is a dynamic process in neonates, which can be moderated by preterm birth, the ALPS index could serve as a sensitive biomarker for monitoring this process. ANN NEUROL 2024.
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Background The role of perivascular space (PVS) dysfunction in obstructive sleep apnea (OSA) requires further study. Purpose To compare MRI indexes of PVS across patients with differing severities of OSA and relate them with disease characteristics and treatment. Materials and Methods This single-center prospective study included healthy controls (HCs) and patients with complaints of snoring who underwent MRI and cognitive evaluation between June 2021 and December 2022. Participants with complaints of snoring were classified into four groups (snoring, mild OSA, moderate OSA, and severe OSA). PVS networks were assessed at MRI using PVS volume fraction, extracellular free water (FW), and diffusion tensor imaging analysis along the PVS (DTI-ALPS). One-way analysis of variance and Pearson correlation were used for analysis. Alterations in PVS indexes and cognitive performance after treatment were assessed in 15 participants with moderate OSA. Results A total of 105 participants (mean age, 33.4 years ± 8.9 [SD]; 80 males) and 50 HCs (mean age, 37.0 years ± 8.6; 33 males) were included. Higher mean PVS volume fraction was observed in participants with severe OSA (n = 23) than in patients with mild OSA (n = 36) (0.11 vs 0.10; P = .03). Participants with severe OSA exhibited higher mean FW index (0.11) than both HCs (0.10; P < .001) and patients with mild OSA (0.10; P = .003). All patient groups had lower DTI-ALPS than HCs (range, 1.5-1.9 vs 2.1; all P < .001). DTI-ALPS correlated with cognitive performance on the Stroop Color and Word Test (r range, -0.23 to -0.24; P value range, .003-.005). After treatment, PVS indexes changed (P value range, <.001 to .01) and cognitive performance improved (P value range, <.001 to .03). Conclusion Differences in PVS indexes were observed among participants with differing severities of OSA and HCs. Indexes correlated with measures of cognitive function, and changes in indexes and improvement in cognitive performance were observed after treatment in participants with moderate OSA. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Port in this issue.
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Disfunção Cognitiva , Imageamento por Ressonância Magnética , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/diagnóstico por imagem , Apneia Obstrutiva do Sono/complicações , Masculino , Feminino , Estudos Prospectivos , Adulto , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Sistema Glinfático/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The promoter variant rs17111237 in the CEP128 closely relates to radiotherapy (RT)-related brain necrosis in nasopharyngeal carcinoma (NPC) patients. PURPOSE: To explore RT-related dynamic alterations in brain morphology and their potential genetic mechanism, and to explore the modulatory effects of CEP128 genetic variants on RT-related brain morphological alterations in NPC patients. STUDY TYPE: Prospective, longitudinal. POPULATION: One hundred one patients with histopathologic ally-proven NPC (age 41.64 ± 9.63, 46 male), analyzed at baseline (pre-RT), 3-months post-RT and 6 months post-RT, and 19 sex-, age- and education-matched healthy controls. FIELD STRENGTH/SEQUENCE: 3D gradient echo brain volume (3D-BRAVO) and diffusion-weighted single-shot spin-echo echo-planar sequences at 3.0 T. ASSESSMENT: rs17111237 in CEP128 was detected by Sanger sequencing. Structural and diffusion images were processed with FreeSurfer and FSL. Morphometric similarity network (MSN) was constructed with nine cortical indices derived from structural and diffusion images. STATISTICAL TESTS: One-way ANOVA, chi-square test. Pearson's correlation analysis was conducted to measure the relationship between CEP128 gene-expression level in human brain and MSN alterations. Repeated analysis of variance performed to assess group differences in MSN and the modulatory effects of the CEP128 gene within patients. Significance level: P < 0.05, false-discovery rate correction. RESULTS: RT-related significant widespread MSN alterations were observed in the cortices of NPC patients. Notably, regional MSN alterations had a weak but significant negative correlation with the cortical pattern of CEP128 gene expression (r = -0.152). Furthermore, rs17111237 in the CEP128 had significant modulatory effects on the observed MSN alterations in NPC patients, with the modulatory effects being most obvious at 3 months post-RT. CONCLUSIONS: MSN has potential to serve as a sensitive biomarker to detect RT-related brain injury. Inter-brain regional and inter-patient variability of RT-related brain injuries may be attributed to the cortical expression of the CEP128 gene and the modulatory effects of the promoter variant rs17111237 in CEP128. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Lesões Encefálicas , Neoplasias Nasofaríngeas , Humanos , Masculino , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Lesões Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Estudos ProspectivosRESUMO
BACKGROUND: Patients with hepatitis B virus-related cirrhosis (HBV-RC) exhibit progressive neurologic dysfunction from primary sensorimotor to high-order cognition, as their disease advances. However, the exact neurobiologic mechanisms and the potential association with gene-expression profiles are not fully understood. PURPOSE: To explore the hierarchical disorganization in the large-scale functional connectomes in HBV-RC patients and to investigate its potential underlying molecular basis. STUDY TYPE: Prospective. POPULATION: Fifty HBV-RC patients and 40 controls (Cohort 1) and 30 HBV-RC patients and 38 controls (Cohort 2). FIELD STRENGTH/SEQUENCE: Gradient-echo echo-planar and fast field echo sequences at 3.0 T (Cohort 1) and 1.5 T (Cohort 2). ASSESSMENT: Data were processed with Dpabi and the BrainSpace package. Gradient scores were evaluated from global to voxel level. Cognitive measurement and patients grouping were based on psychometric hepatic encephalopathy scores. The whole-brain microarray-based gene-expression data were obtained from the AIBS website. STATISTICAL TESTS: One-way ANOVA, chi-square test, two-sample t-test, Kruskal-Wallis test, Spearman's correlation coefficient (r), the gaussian random field correction, false discovery rate (FDR) correction and the Bonferroni correction. Significance level: P < 0.05. RESULTS: HBV-RC patients exhibited a robust and replicable connectome gradient dysfunction, which was significantly associated with the gene-expression profiles in both cohorts (r = 0.52 and r = 0.56, respectively). The most correlated genes were enriched in γ-aminobutyric acid (GABA) and GABA-related receptor genes (FDR q value <0.05). Moreover, the connectome gradient dysfunction at network level observed in HBV-RC patients correlated with their poor cognitive performance (Cohort 2: visual network, r = -0.56; subcortical network, r = 0.66; frontoparietal network, r = 0.51). DATA CONCLUSION: HBV-RC patients had hierarchical disorganization in the large-scale functional connectomes, which may underly their cognitive impairment. In addition, we showed the potential molecular mechanism of the connectome gradient dysfunction, which suggested the importance of GABA and GABA-related receptor genes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Conectoma , Vírus da Hepatite B , Humanos , Vírus da Hepatite B/fisiologia , Estudos Prospectivos , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/genética , Ácido gama-AminobutíricoRESUMO
BACKGROUND: Polyvinyl alcohol (PVA) is one of the most widely used water-soluble polymers with remarkable mechanical properties. However, water-soluble polymers are among the major organic pollutants of streams, river, and marine ecosystems. Once dispersed in aqueous systems, they can directly interfere with the life cycle of aquatic organisms via direct toxic effects. There is thus an urgent need for microorganisms or enzymes that can efficiently degrade them. Oxidized PVA hydrolase plays an important role in the pathway of PVA biodegradation. It is the key enzyme in the second step of the pathway for complete degradation of PVA. METHODS AND RESULTS: The s-oph gene was cloned from the laboratory-isolated strain Sphingopyxis sp. M19. This gene was expressed in the Escherichia coli system pET32a/s-oph expression vector, with the products forming an inclusion body. By binding with a molecular chaperone, pET32a/s-oph/BL21 (DE3)/pGro7 was successfully constructed, which enabled the s-oph gene to be solubly expressed in E. coli. The protein encoded by the s-oph gene was purified at a yield of 16.8 mg L-1, and its catalytic activity reached 852.71 U mg-1. In the s-oph enzyme reaction system, the efficiency of PVA degradation was increased to 233.5% compared with that of controls. CONCLUSIONS: The s-oph enzyme exhibited the characteristics of being able to degrade PVA with high efficiency, specificity, and stability. This enzyme has good potential for practical application in ameliorating plastic pollution and protecting the environment.
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Arildialquilfosfatase , Álcool de Polivinil , Ecossistema , Escherichia coli/genética , PolímerosRESUMO
Pathogenic variants in the v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue (MAF) encoding a transcription factor (from a unique subclass of basic leucine zipper transcription factors) are associated with isolated congenital cataracts (CCs) and Aymé-Gripp syndrome (AYGRPS). We collected detailed disease histories from, and performed comprehensive ophthalmic and systemic examinations in 269 patients with CCs; we then performed whole-exome sequencing. Pathogenicity assessments were evaluated using multiple predictive tools. The clinical validities of the reported gene-disease relationships for MAF genes (MAF-CCs and MAF-AYGRPS) were assessed using the ClinGen gene curation framework. We identified two novel (c.173C>A, p.Thr58Asn and c.947T>C, p. Leu316Pro) variants and one known (c.173C>T, p.Thr58Ile) MAF missense variant in three patients. We described novel phenotypes including cleft palate, macular hypoplasia, and retinal neovascularization in the peripheral avascular area and analyzed the genotype-phenotype correlations. We demonstrated associations of variants in the MAF C-terminal DNA-binding domain with CCs and associations of variants in the N-terminal transactivation domain of MAF with AYGRPS. We thus expand the genotypic and phenotypic spectrum of the MAF gene. The ClinGen gene curation framework results suggested that variants in different domains of MAF are associated with different diseases.
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Catarata , Proteínas Proto-Oncogênicas c-maf , Catarata/patologia , China , Fácies , Genótipo , Transtornos do Crescimento , Perda Auditiva Neurossensorial , Humanos , Deficiência Intelectual , Fenótipo , Proteínas Proto-Oncogênicas c-maf/genéticaRESUMO
OBJECTIVES: To investigate the effects of standard radiotherapy on temporal white matter (WM) and its relationship with radiation necrosis (RN) in patients with nasopharyngeal carcinoma (NPC), and to determine the predictive value of WM volume alterations at the early stage for RN occurrence at the late-delay stage. METHODS: Seventy-four treatment-naive NPC patients treated with standard radiotherapy were longitudinally followed up for 36 months. Structural MRIs were collected at multiple time points during the first year post-radiotherapy. Longitudinal structural images were processed using FreeSurfer. Linear mixed models were used to delineate divergent trajectories of temporal WM changes between patients who developed RN and who did not. Four machine learning methods were used to construct predictive models for RN with temporal WM volume alterations at early-stage. RESULTS: The superior temporal gyrus (STG) had divergent atrophy trajectories in NPC patients with different outcomes (RN vs. NRN) post-radiotherapy. Patients with RN showed more rapid atrophy than those with NRN. A predictive model constructed with temporal WM volume alterations at early-stage post-radiotherapy had good performance for RN; the areas under the curve (AUC) were 0.879 and 0.806 at 1-3 months and 6 months post-radiotherapy, respectively. Moreover, the predictive model constructed with absolute temporal volume at 1-3 months post-radiotherapy also presented good performance; the AUC was 0.842, which was verified by another independent dataset (AUC = 0.773). CONCLUSIONS: NPC patients with RN had more sharp atrophy in the STG than those with NRN. Temporal WM volume at early-stage post-radiotherapy may serve as an in vivo biomarker to identify and predict RN occurrence. KEY POINTS: ⢠The STG had divergent atrophy trajectories in NPC patients with different outcomes (RN vs. NRN) post-radiotherapy. ⢠Although both groups exhibited time-dependent atrophy in the STG, the patients with RN showed a more rapid volume decrease than those with NRN. ⢠Temporal WM volume alteration (or absolute volume) at the early stage could predict RN occurrence at the late-delay stage after radiotherapy.
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Neoplasias Nasofaríngeas , Lesões por Radiação , Substância Branca , Atrofia/patologia , Biomarcadores , Humanos , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Necrose/patologia , Lesões por Radiação/etiologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
Adsorption of lead (Pb2+) onto the montmorillonite (Mt) surface is one of the key approaches to remove Pb2+ in geological and environmental engineering. Temperature and initial Pb2+ concentration are two essential factors that influence the adsorption capacity of Mt on absorbing Pb2+. However, the nanoscale governing mechanism of temperature and initial concentration on Pb2+ adsorbing of Mt is still unclear. This research performed comprehensively molecular dynamics (MD) simulations to investigate how temperature and initial concentration affect the dynamic Pb2+ adsorption of Mt nanopore. The Pb2+ removal ratio shows a two-stage variation with the increase of initial Pb2+ concentration. Temperature controls the maximum initial Pb2+ concentration for complete Pb2+ removal by changing the maximum adsorption energy of Mt. Temperature also influences the maximum adsorption capacity and Pb2+ removal ratio of Mt nanopore indirectly by changing diffusion and hydration state of Pb2+. The initial Pb2+ concentration corresponding to the maximum adsorption energy coincides with the maximum initial Pb2+ concentration determined by the Pb2+ removal ratio. Lower adsorption energy and higher level of hydration and diffusion make Pb2+ absorbing on Mt surface become more difficult, reducing the Pb2+ adsorbing capacity of Mt. The initial Pb2+ concentration influences adsorption capacity and Pb2+ removal ratio not only via altering the quantity of Pb2+ but also through controlling the adsorption energy of Mt, as well as the diffusion and hydration state of Pb2+. With the increase of initial Pb2+ concentration, the hydration of Pb2+ is weakened while the adsorption energy of Mt and diffusion of Pb2+ are enhanced.
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Nanoporos , Poluentes Químicos da Água , Adsorção , Bentonita , Concentração de Íons de Hidrogênio , Cinética , Chumbo , Temperatura , Poluentes Químicos da Água/análiseRESUMO
Owing to its strong environmental suitability to adverse abiotic stress conditions, common vetch (Vicia sativa) is grown worldwide for both forage and green manure purposes and is an important protein source for human consumption and livestock feed. The germination of common vetch seeds and growth of seedlings are severely affected by salinity stress, and the response of common vetch to salinity stress at the molecular level is still poorly understood. In this study, we report the first comparative transcriptomic analysis of the leaves and roots of common vetch under salinity stress. A total of 6361 differentially expressed genes were identified in leaves and roots. In the roots, the stress response was dominated by genes involved in peroxidase activity. However, the genes in leaves focused mainly on Ca2+ transport. Overexpression of six salinity-inducible transcription factors in yeast further confirmed their biological functions in the salinity stress response. Our study provides the most comprehensive transcriptomic analysis of common vetch leaf and root responses to salinity stress. Our findings broaden the knowledge of the common and distinct intrinsic molecular mechanisms within the leaves and roots of common vetch and could help to develop common vetch cultivars with high salinity tolerance.
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Vicia sativa , Regulação da Expressão Gênica de Plantas , Humanos , Folhas de Planta/genética , Salinidade , Estresse Salino/genética , Estresse Fisiológico/genética , Transcriptoma , Vicia sativa/genéticaRESUMO
BACKGROUND: The diseased-related dynamic functional network connectivity (dFNC) disruption and its relationship with cognitive impairment in hepatitis B virus-related cirrhosis (HBV-RC) patients with minimal hepatic encephalopathy (MHE) and no MHE (NMHE) remain unknown. This knowledge would help identify MHE pathophysiology and monitor disease progression in HBV-RC patients. PURPOSE: To investigate the dFNC in patients with NMHE and MHE and the relationship between dFNC indices with the psychometric hepatic encephalopathy score (PHES). STUDY TYPE: Prospective. POPULATION: Thirty HBV-RC patients (including 17 NMHE and 13 MHE) and 38 healthy controls (HC). FIELD STRENGTH/SEQUENCE: A 1.5 T MRI and gradient-echo echo-planar imaging and fast field echo three-dimensional T1-weighted imaging. ASSESSMENT: The independent components, dFNC matrix and dFNC indices (mean dwell times [DT], number of states, number of transitions, and fraction time in each state), were obtained through GIFT package. Cognitive measurement and patients grouping were based on PHES tests. STATISTICAL TESTS: One-way ANOVA, chi-square test, two-sample t-test, Kruskal-Wallis test, spearman's correlation analysis and the false discovery rate. Significance level: P < 0.05. RESULTS: Compared to HC (21.1 ± 4.02), the DT of state 1 decreased in NMHE (9.0 ± 3.04, P = 0.062, 95% confidence interval [CI] is -0.65 to 24.88) and significantly in MHE stage (1.2 ± 1.01) and was significantly correlated with PHES (r = 0.5) for all patients. The DT of state 2 increased gradually in NMHE (75.2 ± 13.10, P = 0.052, 95% CI, -54.23 to 0.28) and significantly in MHE stage (94.6 ± 15.61) when compared to HC (48.2 ± 6.97). Moreover, the connectivity between cognitive control network (CCN) and visual network (VIS) in state 1 (0.7 ± 0.79) and between default mode (DMN) and VIS in state 2 (-0.2 ± 0.29) decreased significantly in MHE when compared to HC (0.1 ± 0.68 for CCN-VIS in state 1 and 0.1 ± 0.17 for DMN-VIS for state 2). DATA CONCLUSION: dFNC exhibited progressive impairment as the disease advances in patients with HBV-RC. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Encefalopatia Hepática , Vírus da Hepatite B , Encéfalo/patologia , Encefalopatia Hepática/diagnóstico por imagem , Encefalopatia Hepática/patologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Imageamento por Ressonância Magnética , Estudos ProspectivosRESUMO
BACKGROUND: Common vetch (Vicia sativa L.) is an important self-pollinating annual forage legume and is of interest for drought prone regions as a protein source to feed livestock and human consumption. However, the development and production of common vetch are negatively affected by drought stress. Plants have evolved common or distinct metabolic pathways between the aboveground and underground in response to drought stress. Little is known regarding the coordinated response of aboveground and underground tissues of common vetch to drought stress. RESULTS: Our results showed that a total of 30,427 full-length transcripts were identified in 12 samples, with an average length of 2278.89 bp. Global transcriptional profiles of the above 12 samples were then analysed via Illumina-Seq. A total of 3464 and 3062 differentially expressed genes (DEGs) were identified in the leaves and roots, respectively. Gene Ontology (GO) enrichment analyses identified that the dehydrin genes and Δ1-pyrroline-5-carboxylate synthase were induced for the biosynthesis of proline and water conservation. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results indicated that the DEGs were significantly enriched in hormone signal transduction, starch and sucrose metabolism, and arginine and proline metabolism, and various drought response candidate genes were also identified. Abscisic acid (ABA; the AREB/ABF-SnRK2 pathway) regulates the activity of AMY3 and BAM1 to induce starch degradation in leaves and increase carbon export to roots, which may be associated with the drought stress responses in common vetch. Among the co-induced transcription factors (TFs), AREB/ABF, bHLH, MYB, WRKY, and AP2/ERF had divergent expression patterns and may be key in the crosstalk between leaves and roots during adaption to drought stress. In transgenic yeast, the overexpression of four TFs increased yeast tolerance to osmotic stresses. CONCLUSION: The multipronged approach identified in the leaves and roots broadens our understanding of the coordinated mechanisms of drought response in common vetch, and further provides targets to improve drought resistance through genetic engineering.
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Secas , Pressão Osmótica , Folhas de Planta/genética , Raízes de Plantas/genética , Vicia sativa/genética , Ácido Abscísico/metabolismo , Arginina/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Prolina/metabolismo , Fatores de Transcrição/metabolismo , Transcriptoma , Regulação para CimaRESUMO
To discuss the microbial structure that develops during the course of compost burials of polyvinyl alcohol (PVA)-based material and analyze the effect of the degree of PVA alcoholysis on the PVA-degrading ability of each strain. Two bacterial strains exhibiting a high level of PVA-degrading ability and two mixed cultures were isolated from compost loaded with PVA-based material. The rod-shaped Gram-positive bacterium DG22 was identified by 16S rDNA sequencing analysis as Bacillus sp. DG22, and the rod-shaped Gram-negative bacterium DG14 was identified as Paenibacillus sp. DG14. Biodegradation rates were determined by iodometric analysis within 8 days of culturing on selective media. The biodegradation rates for PVA1799 by DG22, DG14, T1 (mixed culture from a 36-month burial), and T2 (mixed culture from a 24-month burial) were 54.47, 46.59, 69.62, and 79.04%, respectively, and those of PVA1788 were 74.99, 67.27, 54.43, and 50.76%, respectively. DG22 and DG14 are the first known Bacillus sp. and Paenibacillus sp. able to utilize PVA solely. However, the higher degree of PVA alcoholysis (AD) had a negative effect on the biodegradation of PVA.
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Bactérias/metabolismo , Compostagem , Álcool de Polivinil/metabolismo , Bacillus/isolamento & purificação , Bacillus/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodegradação Ambiental , Paenibacillus/isolamento & purificação , Paenibacillus/metabolismo , Filogenia , RNA Ribossômico 16S/genéticaRESUMO
OBJECTIVE: To breed Aspergillus oryzae strains with high fructosyltransferase (FTase) activity using intraspecific protoplast fusion via genome-shuffling. RESULTS: A candidate library was developed using UV/LiCl of the conidia of A. oryzae SBB201. By screening for enzyme activity and cell biomass, two mutants (UV-11 and UV-76) were chosen for protoplast fusion and subsequent genome shuffling. After three rounds of genome recombination, a fusion mutant RIII-7 was obtained. Its FTase activity was 180 U g-1, approximately double that of the original strain, and RIII-7 was genetically stable. In fermentation culture, FTase activity of the genome-shuffled strain reached a maximum of 353 U g-1 using substrate-feeding method, and this value was approximately 3.4-times higher than that of the original strain A. oryzae SBB201. CONCLUSIONS: Intraspecific protoplast fusion of A. oryzae significantly enhanced FTase activity and generated a potentially useful strain for industrial production.
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Aspergillus oryzae/enzimologia , Embaralhamento de DNA/métodos , Genoma Fúngico , Hexosiltransferases/biossíntese , Aspergillus oryzae/efeitos dos fármacos , Fermentação/efeitos dos fármacos , Instabilidade Genômica , Fusão de Membrana/efeitos dos fármacos , Mutagênese/genética , Mutação/genética , Protoplastos/efeitos dos fármacos , Protoplastos/metabolismo , Regeneração/efeitos dos fármacos , Sacarose/farmacologiaRESUMO
Radioresistance is a major challenge during the treatment of breast cancer. A further understanding of the mechanisms of radioresistance could provide strategies to address this challenge. In our study, we compared the expression of miR-200c in four distinct breast cancer cell lines: two representative basal cancer cells (MDA-MB-231 and BT549) vs. two representative luminal cancer cells (MCF-7 and BT474). The results revealed practically lower expression of miR-200c in the two basal cancer cell lines and higher expression of miR-200c in luminal cancer cells compared to the normal breast epithelial cell line MCF-10A. Ectopic expression of miR-200c in MDA-MB-231 cells inhibited irradiation-induced autophagy and sensitized the breast cancer cells to irradiation. We also identified UBQLN1 as a direct functional target of miR-200c involved in irradiation-induced autophagy and radioresistance. In 35 human breast cancer tissue samples, we detected an inverse correlation between the expression of miR-200c vs. UBQLN1 and LC3. These results indicate that the identified miR-200c/UBQLN1-mediated autophagy pathway may help to elucidate radioresistance in human breast cancer and might represent a therapeutic strategy.
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Autofagia/efeitos da radiação , Neoplasias da Mama/genética , Carcinoma Basocelular/genética , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Ciclo Celular/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Tolerância a Radiação , Proteínas Adaptadoras de Transdução de Sinal , Apoptose/efeitos da radiação , Proteínas Relacionadas à Autofagia , Western Blotting , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Carcinoma Basocelular/radioterapia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos da radiação , Células Cultivadas , Transição Epitelial-Mesenquimal , Feminino , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Luciferases/metabolismo , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The function of autophagy in cancer has been intensively studied as a possible therapeutic target due to its unique ability to influence the cancer cells' resistance to chemotherapy and radiation treatment. p53 is a pivotal tumor suppressor that induces apoptosis, cell cycle arrest, and senescence in response to various stresses, also playing an important role in the regulation of radiosensitivity. Autophagy may either promote or inhibit the survival of tumor cells, while it was found to change along with the status of p53 in cancer cells. In this mini review, we aimed to provide an overview of the intricate relationship between autophagy and the status of p53 which plays an important role in radiosensitivity. Since autophagy can react to radiation differently in cancer cells with different p53 statuses, future work elucidating the interaction between autophagy and p53 in response to radiation might provide more insight into targeted cancer radiotherapy.
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Autofagia , Neoplasias/radioterapia , Tolerância a Radiação , Proteína Supressora de Tumor p53/fisiologia , Humanos , Neoplasias/patologia , Transdução de Sinais/fisiologiaRESUMO
Antibiotic resistance, one of the major medical threats worldwide, can be selected and induced by metals through multiple mechanisms such as co-resistance, cross-resistance, and co-regulation. Compared with co-resistance and cross-resistance which are attributed to the physically or functionally linked metal and antibiotic resistance genes, co-regulation of antibiotic resistance genes by metal-responsive regulators and pathways is much more complex and elusive. Here, we discussed the main mechanisms by which antibiotic resistance is regulated in response to metals and showed recent attempts to combat antibiotic resistance by interfering with metal-based signalling pathways. Further efforts to depict the intricate metal-based regulatory network of antibiotic resistance will provide tremendous opportunities for the discovery of novel anti-resistance targets, and blocking or rewiring the metal-based signalling pathways is emerging as a promising stratagem to reverse bacterial resistance to antibiotics and rejuvenate the efficacy of conventional antibiotics.
Assuntos
Antibacterianos , Bactérias , Farmacorresistência Bacteriana , Regulação Bacteriana da Expressão Gênica , Metais , Antibacterianos/farmacologia , Metais/metabolismo , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/metabolismo , Transdução de SinaisRESUMO
This study aimed to evaluate spectacle-wearing compliance and identify the determinants associated with it in infants with bilateral corrective refractive errors. Infants agedâ <â 3 years with bilateral corrective refractive errors who were supplied with spectacles forâ >â 1 month were enrolled at the pediatric comprehensive clinic of Zhongshan Ophthalmic Center. Spectacle-wearing compliance was evaluated by calculating the percentage of spectacle-wearing time in the awake time (STIT), and its potential determinants were identified based on interviews with the infants' caregivers using univariate and multivariate logistic regression analysis. Pearson correlation analysis was performed to further determine the degree of correlation between spectacle-wearing compliance and weight of spectacles. A total of 366 infants (age: 20.85â ±â 9.06 months, male: 54.92%) were included. The mean percentage of STIT was 64.00%±41.69%. The communication between caregivers of different infants regarding spectacle-wearing experience (Pâ =â .004, ORâ =â 2.290, 95% confidence interval [CI] for ORâ =â 1.301-4.029), perceptions of spectacle-wearing importance (Pâ =â .000, ORâ =â 6.337, 95% CI for ORâ =â 3.664-10.961), and weight of spectacles (Pâ =â .000, ORâ =â 7.271, 95% CI for ORâ =â 4.141-12.769) were significantly associated with spectacle-wearing compliance. Besides, spectacle-wearing compliance was positively correlated with the weight of spectacles (Pâ <â .01), exhibiting a decreasing trend with the weight of spectacles. Overall, spectacle-wearing compliance requires improvement. Moreover, efficient strategies aimed at improving spectacle-wearing compliance, such as enhancing communication between caregivers of different infants regarding spectacle-wearing experience, raising awareness about the importance of wearing spectacles, and reducing the weight of spectacles, are urgently needed.
Assuntos
Óculos , Erros de Refração , Criança , Humanos , Masculino , Lactente , Pré-Escolar , Erros de Refração/terapia , Instituições de Assistência Ambulatorial , Comunicação , Correlação de Dados , Cooperação do PacienteRESUMO
Background: This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs). Methods: Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2-3, 3-4, 4-5, and 5-6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed. Results: A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2-6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson's correlation test). Conclusion: Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2-6 years may benefit visual acuity rehabilitation.
RESUMO
PURPOSE: To characterize the morphology of persistent pupillary membranes (PPMs) in pediatric patients and explore the corresponding surgical approaches. SETTING: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: Prospective observational study. METHODS: Consecutive pediatric patients with PPMs who underwent surgery from April 2020 to July 2022 were included. PPM morphology was assessed and categorized according to its anatomic relationship with crystalline lens and distribution of iris strands. The surgical approaches for different morphologies of PPMs were described in detail. The visual outcome and operation-related complications were recorded. RESULTS: 31 eyes from 19 patients were included with the mean age of 7.2 years. 3 morphological variants of PPMs were observed: type I (51.6%, 16/31), a spider-like appearance and no adhesion to the anterior lens capsule (ALC); type II (38.7%, 12/31), a loose central adherence to the ALC and partially thick iris strands attached to the iris collarette; type III (9.7%, 3/31), a tight central adherence to the ALC and only silk-like iris strands. Surgeries were performed with a natural pupil size in type I, while dilated pupil in the other types. The adhesions between PPM and the ALC were separated by viscoelastic injection in type II and by discission needles in type III. The corrected distance visual acuity was significantly improved from 0.34 ± 0.18 logMAR preoperatively to 0.17 ± 0.09 logMAR postoperatively ( P < .001). No operation-related complications were observed during 9.5-month follow-up. CONCLUSIONS: PPMs were categorized into 3 types according to their different morphologies, which helped to determine the best surgical strategy.