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1.
Cell ; 163(2): 445-55, 2015 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-26451488

RESUMO

RNA-directed DNA methylation in Arabidopsis thaliana is driven by the plant-specific RNA Polymerase IV (Pol IV). It has been assumed that a Pol IV transcript can give rise to multiple 24-nt small interfering RNAs (siRNAs) that target DNA methylation. Here, we demonstrate that Pol IV-dependent RNAs (P4RNAs) from wild-type Arabidopsis are surprisingly short in length (30 to 40 nt) and mirror 24-nt siRNAs in distribution, abundance, strand bias, and 5'-adenine preference. P4RNAs exhibit transcription start sites similar to Pol II products and are featured with 5'-monophosphates and 3'-misincorporated nucleotides. The 3'-misincorporation preferentially occurs at methylated cytosines on the template DNA strand, suggesting a co-transcriptional feedback to siRNA biogenesis by DNA methylation to reinforce silencing locally. These results highlight an unusual mechanism of Pol IV transcription and suggest a "one precursor, one siRNA" model for the biogenesis of 24-nt siRNAs in Arabidopsis.


Assuntos
Arabidopsis/metabolismo , RNA de Plantas/genética , RNA Interferente Pequeno/genética , Adenina/metabolismo , Arabidopsis/enzimologia , Arabidopsis/genética , Metilação de DNA , RNA Polimerases Dirigidas por DNA/metabolismo , Modelos Biológicos , Sítio de Iniciação de Transcrição
2.
Proc Natl Acad Sci U S A ; 120(28): e2220190120, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37399401

RESUMO

The MYC proto-oncogene contributes to the pathogenesis of more than half of human cancers. Malignant transformation by MYC transcriptionally up-regulates the core pre-mRNA splicing machinery and causes misregulation of alternative splicing. However, our understanding of how splicing changes are directed by MYC is limited. We performed a signaling pathway-guided splicing analysis to identify MYC-dependent splicing events. These included an HRAS cassette exon repressed by MYC across multiple tumor types. To molecularly dissect the regulation of this HRAS exon, we used antisense oligonucleotide tiling to identify splicing enhancers and silencers in its flanking introns. RNA-binding motif prediction indicated multiple binding sites for hnRNP H and hnRNP F within these cis-regulatory elements. Using siRNA knockdown and cDNA expression, we found that both hnRNP H and F activate the HRAS cassette exon. Mutagenesis and targeted RNA immunoprecipitation implicate two downstream G-rich elements in this splicing activation. Analyses of ENCODE RNA-seq datasets confirmed hnRNP H regulation of HRAS splicing. Analyses of RNA-seq datasets across multiple cancers showed a negative correlation of HNRNPH gene expression with MYC hallmark enrichment, consistent with the effect of hnRNP H on HRAS splicing. Interestingly, HNRNPF expression showed a positive correlation with MYC hallmarks and thus was not consistent with the observed effects of hnRNP F. Loss of hnRNP H/F altered cell cycle progression and induced apoptosis in the PC3 prostate cancer cell line. Collectively, our results reveal mechanisms for MYC-dependent regulation of splicing and point to possible therapeutic targets in prostate cancers.


Assuntos
Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H , Neoplasias da Próstata , Masculino , Humanos , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , Splicing de RNA/genética , Proteínas de Ligação a RNA/metabolismo , Éxons/genética , Processamento Alternativo/genética , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo
3.
FASEB J ; 38(6): e23538, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38482729

RESUMO

Stem cells respond and remember mechanical cues from the microenvironment, which modulates their therapeutic effects. Chromatin organization and energy metabolism regulate the stem cell fate induced by mechanical cues. However, the mechanism of mechanical memory is still unclear. This study aimed to investigate the effects of mechanical amplitude, frequency, duration, and stretch cycle on mechanical memory in mesenchymal stem cells. It showed that the amplitude was the dominant parameter to the persistence of cell alignment. F-actin, paxillin, and nuclear deformation are more prone to be remolded than cell alignment. Stretching induces transcriptional memory, resulting in greater transcription upon subsequent reloading. Cell metabolism displays mechanical memory with sustained mitochondrial fusion and increased ATP production. The mechanical memory of chromatin condensation is mediated by histone H3 lysine 27 trimethylation, leading to much higher smooth muscle differentiation efficiency. Interestingly, mechanical memory can be transmitted based on direct cell-cell interaction, and stretched cells can remodel the metabolic homeostasis of static cells. Our results provide insight into the underlying mechanism of mechanical memory and its potential benefits for stem cell therapy.


Assuntos
Cromatina , Células-Tronco Mesenquimais , Cromatina/metabolismo , Estresse Mecânico , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Músculo Liso , Proliferação de Células
4.
Cancer Immunol Immunother ; 73(8): 149, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833018

RESUMO

Despite the successful application of programmed cell death ligand 1 (PD-L1)-blocking strategies in some types of cancers and well-established prognostic indicators in pancreatic ductal adenocarcinoma (PDAC), the biological and clinical implications of the methylation status of PD-L1/PD-L2 in PDAC remain largely unknown. Therefore, this study aimed to explore the biological role of PD-L1/PD-L2 methylation and its association with clinicopathological features, clinical outcomes, and the immune microenvironment by analyzing the data on PD-L1/PD-L2 methylation and mRNA expression in PDAC cohorts obtained from the Cancer Genome Atlas and International Cancer Genome Consortium. The correlation between PD-L1 promoter methylation and PD-L1 expression and survival was further validated in an independent validation cohort (Peking Union Medical College Hospital [PUMCH] cohort) using pyrosequencing and immunohistochemistry. These results demonstrated that hypomethylation of the PD-L1 promoter was strongly associated with upregulated PD-L1 expression and shorter overall survival in PDAC. Multivariate Cox regression analyses revealed that the PD-L1 promoter methylation was an independent prognostic factor. PD-L1 promoter hypomethylation and high expression were related to aggressive clinical phenotypes. Moreover, both PD-L1 and PD-L2 methylation correlated with immune cell infiltration and the expression of immune checkpoint genes. PD-L1 promoter methylation status was further validated as an independent prognostic biomarker in patients with PDAC using the PUMCH cohort. The prognostic significance of PD-L1 promoter methylation was more discriminative in tumors with perineural/lymphovascular invasion and distant metastasis than in those without perineural/lymphovascular invasion and distant metastasis. In summary, the methylation status of the PD-L1 promoter is a promising biomarker for survival outcomes, immune infiltration, and the potential immune benefits of immunotherapy in PDAC.


Assuntos
Antígeno B7-H1 , Carcinoma Ductal Pancreático , Metilação de DNA , Neoplasias Pancreáticas , Regiões Promotoras Genéticas , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Regiões Promotoras Genéticas/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Idoso , Regulação Neoplásica da Expressão Gênica
5.
Biostatistics ; 24(4): 833-849, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-35861621

RESUMO

Cluster randomized trials often exhibit a three-level structure with participants nested in subclusters such as health care providers, and subclusters nested in clusters such as clinics. While the average treatment effect has been the primary focus in planning three-level randomized trials, interest is growing in understanding whether the treatment effect varies among prespecified patient subpopulations, such as those defined by demographics or baseline clinical characteristics. In this article, we derive novel analytical design formulas based on the asymptotic covariance matrix for powering confirmatory analyses of treatment effect heterogeneity in three-level trials, that are broadly applicable to the evaluation of cluster-level, subcluster-level, and participant-level effect modifiers and to designs where randomization can be carried out at any level. We characterize a nested exchangeable correlation structure for both the effect modifier and the outcome conditional on the effect modifier, and generate new insights from a study design perspective for conducting analyses of treatment effect heterogeneity based on a linear mixed analysis of covariance model. A simulation study is conducted to validate our new methods and two real-world trial examples are used for illustrations.


Assuntos
Projetos de Pesquisa , Humanos , Tamanho da Amostra , Análise por Conglomerados , Ensaios Clínicos Controlados Aleatórios como Assunto , Simulação por Computador
6.
Cerebellum ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558026

RESUMO

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

7.
Stat Med ; 43(5): 890-911, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38115805

RESUMO

Stepped wedge design is a popular research design that enables a rigorous evaluation of candidate interventions by using a staggered cluster randomization strategy. While analytical methods were developed for designing stepped wedge trials, the prior focus has been solely on testing for the average treatment effect. With a growing interest on formal evaluation of the heterogeneity of treatment effects across patient subpopulations, trial planning efforts need appropriate methods to accurately identify sample sizes or design configurations that can generate evidence for both the average treatment effect and variations in subgroup treatment effects. To fill in that important gap, this article derives novel variance formulas for confirmatory analyses of treatment effect heterogeneity, that are applicable to both cross-sectional and closed-cohort stepped wedge designs. We additionally point out that the same framework can be used for more efficient average treatment effect analyses via covariate adjustment, and allows the use of familiar power formulas for average treatment effect analyses to proceed. Our results further sheds light on optimal design allocations of clusters to maximize the weighted precision for assessing both the average and heterogeneous treatment effects. We apply the new methods to the Lumbar Imaging with Reporting of Epidemiology Trial, and carry out a simulation study to validate our new methods.


Assuntos
Projetos de Pesquisa , Heterogeneidade da Eficácia do Tratamento , Humanos , Estudos Transversais , Ensaios Clínicos Controlados Aleatórios como Assunto , Simulação por Computador , Tamanho da Amostra , Análise por Conglomerados
8.
Am J Epidemiol ; 192(6): 1006-1015, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-36799630

RESUMO

Many studies encounter clustering due to multicenter enrollment and nonmortality outcomes, such as quality of life, that are truncated due to death-that is, missing not at random and nonignorable. Traditional missing-data methods and target causal estimands are suboptimal for statistical inference in the presence of these combined issues, which are especially common in multicenter studies and cluster-randomized trials (CRTs) carried out among the elderly or seriously ill. Using principal stratification, we developed a Bayesian estimator that jointly identifies the always-survivor principal stratum in a clustered/hierarchical data setting and estimates the average treatment effect among them (i.e., the survivor average causal effect (SACE)). In simulations, we observed low bias and good coverage with our method. In a motivating CRT, the SACE and the estimate from complete-case analysis differed in magnitude, but both were small, and neither was incompatible with a null effect. However, the SACE estimate has a clear causal interpretation. The option to assess the rigorously defined SACE estimand in studies with informative truncation and clustering can provide additional insight into an important subset of study participants. Based on the simulation study and CRT reanalysis, we provide practical recommendations for using the SACE in CRTs and software code to support future research.


Assuntos
Modelos Estatísticos , Qualidade de Vida , Humanos , Idoso , Teorema de Bayes , Ensaios Clínicos Controlados Aleatórios como Assunto , Sobreviventes
9.
FASEB J ; 36(3): e22182, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35113455

RESUMO

Pre-pandemic influenza H5N1 vaccine has relatively low immunogenicity and often requires high antigen amounts and two immunizations to induce protective immunity. Incorporation of vaccine adjuvants is promising to stretch vaccine doses during pandemic outbreaks. This study presents a physical radiofrequency (RF) adjuvant (RFA) to conveniently and effectively increase the immunogenicity and efficacy of H5N1 vaccine without modification of vaccine preparation. Physical RFA is based on a brief RF treatment of the skin to induce thermal stress to enhance intradermal vaccine-induced immune responses with minimal local or systemic adverse reactions. We found that physical RFA could significantly increase H5N1 vaccine-induced hemagglutination inhibition antibody titers in murine models. Intradermal H5N1 vaccine in the presence of RFA but not vaccine alone significantly lowered lung viral titers, reduced body weight loss, and improved survival rates after lethal viral challenges. The improved protection in the presence of RFA was correlated with enhanced humoral and cellular immune responses to H5N1 vaccination in both male and female mice, indicating no gender difference of RFA effects in murine models. Our data support further development of the physical RFA to conveniently enhance the efficacy of H5N1 vaccine.


Assuntos
Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antivirais/imunologia , Feminino , Testes de Inibição da Hemaglutinação/métodos , Pulmão/imunologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pandemias/prevenção & controle , Vacinação/métodos
10.
Cerebellum ; 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993636

RESUMO

Ataxia-ocular apraxia 2 (AOA2) is a rare neurodegenerative autosomal recessive disorder with no effective treatment. In this study, we present the case of a patient diagnosed with AOA2, who experienced walking instability and uncoordinated movement. The patient underwent transcranial alternating current stimulation (tACS) treatment for 4 weeks with follow-up after 1 month. The effectiveness of the treatment was evaluated using the International Cooperative Ataxia Rating Scale (ICARS), the Scale for the Assessment and Rating of Ataxia (SARA), the 9-Hole Peg Test (9HPT), and functional near-infrared spectroscopy (fNIRS). Following treatment, the patient's ataxia symptoms showed significant improvement and continued to be alleviated during the follow-up period, suggesting a lasting effect of tACS treatment. Our findings from this case study provide compelling evidence for the potential of tACS as a treatment option for AOA2.

11.
Cerebellum ; 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38117450

RESUMO

The present case study reported a patient diagnosed with hypertrophic olivary degeneration, a rare condition characterized by a trans-neuronal degeneration and signal enhancement in T2-weighted images on magnetic resonance imaging, usually caused by cerebral hemorrhage, cerebral infarction, and trauma. Furthermore, the relevant literature review was performed. The existing pharmacological treatment has limited clinical benefits on the patient. Since spontaneous remission hardly occurs in the disease, there are no other effective treatments. In this case, the patient was a 55-year-old Chinese male who presented progressive gait difficulty for several months due to both-sided ataxia. Neurological examination revealed upper extremity and lower limb bilateral spasticity, ataxia, slurred speech, and dysmetria. Therefore, our study treated the patient through the inventive application of cerebello-spinal transcranial direct current stimulation and body weight-supported treadmill training. After a 4-week treatment, the patient could walk independently, without aid, speeding up by 7%, as well as the ataxia symptoms, and balance has improved significantly. It was demonstrated in this case report that the combination of cerebello-spinal tDCS and body weight-supported treadmill training can be an effective treatment for patients with Hypertrophic olivary degeneration.

12.
Cell Mol Life Sci ; 79(11): 551, 2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-36244032

RESUMO

Periodontal ligament (PDL) cells are a promising tool for periodontal regeneration therapy. Achieving a sufficient number of PDL cells is essential to PDL regeneration. In our study, appropriate flow shear stress (FSS, 1-6 dyn/cm2) promotes the proliferation of PDL cells. FSS remodels cytoskeleton and focal adhesion in a duration-dependent manner. FSS induces PDL cells to form the actin cap within 10 min, flattens the nuclei, and increases the nuclear pore size, which promotes nuclear translocation of Yes-associated protein (YAP). FSS activates p38, which plays a dual function in YAP regulation. p38 regulates the phosphorylation of Akt and cofilin, as well as induced F-actin polymerization to induce YAP activity. In addition, p38 inhibits pLATS and consecutively regulates angiomotin (AMOT) and YAP phosphorylation. AMOT competitively binds to F-actin and YAP to participate in FSS-mediated YAP nuclear translocation and cell proliferation. Taken collectively, our results provide mechanistic insights into the role of p38-AMOT-YAP in FSS-mediated PDL cells proliferation and indicate potential applications in dental regenerative medicine.


Assuntos
Actinas , Ligamento Periodontal , Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Angiomotinas , Proliferação de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Sinalização YAP
13.
Med Sci Monit ; 29: e941486, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37661601

RESUMO

BACKGROUND Inspiratory muscle training (IMT) aims to train inspiratory muscles based mainly on the diaphragm by applying a load resistance during the inspiratory process. Many papers related to IMT have been published in various journals; however, no articles objectively and directly present the development trends and research hotspots of IMT. Therefore, this study used CiteSpace to visually analyze recent IMT-related publications to provide valuable information for future IMT-related studies. MATERIAL AND METHODS CiteSpace was applied to analyze the IMT-related publications by countries, institutions, journals, authors, references, and keywords. RESULTS We included 504 papers. The number of IMT-related publications trended upward between 2009 and 2022. Leuven had the highest number of publications by an institution. The American Journal of Respiratory and Critical Care Medicine was the most frequently co-cited journal. Half of the top 10 references cited were from Journal Citation Reports (JCR) Q1 and half were about the application of IMT in chronic obstructive pulmonary disorder. Gosselink was the author with the highest number of publications and Aldrich was the author with the highest co-citation frequency. The preponderance of studies on the surgical population and postoperative pulmonary complications reflects potential application of IMT in enhanced recovery after surgery. CONCLUSIONS This study provides scholars with important information related to IMT research. It analyzes IMT research trends and status, which can help researchers identify primary topics in the field and find ways to explore new research directions to promote the application of IMT in clinical practice and the cooperation of IMT-related disciplines.


Assuntos
Diafragma , Instalações de Saúde , Humanos , Modalidades de Fisioterapia , Complicações Pós-Operatórias , Período Pós-Operatório
14.
Biom J ; 65(6): e2200002, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35593026

RESUMO

For multicenter randomized trials or multilevel observational studies, the Cox regression model has long been the primary approach to study the effects of covariates on time-to-event outcomes. A critical assumption of the Cox model is the proportionality of the hazard functions for modeled covariates, violations of which can result in ambiguous interpretations of the hazard ratio estimates. To address this issue, the restricted mean survival time (RMST), defined as the mean survival time up to a fixed time in a target population, has been recommended as a model-free target parameter. In this article, we generalize the RMST regression model to clustered data by directly modeling the RMST as a continuous function of restriction times with covariates while properly accounting for within-cluster correlations to achieve valid inference. The proposed method estimates regression coefficients via weighted generalized estimating equations, coupled with a cluster-robust sandwich variance estimator to achieve asymptotically valid inference with a sufficient number of clusters. In small-sample scenarios where a limited number of clusters are available, however, the proposed sandwich variance estimator can exhibit negative bias in capturing the variability of regression coefficient estimates. To overcome this limitation, we further propose and examine bias-corrected sandwich variance estimators to reduce the negative bias of the cluster-robust sandwich variance estimator. We study the finite-sample operating characteristics of proposed methods through simulations and reanalyze two multicenter randomized trials.


Assuntos
Simulação por Computador , Taxa de Sobrevida , Análise por Conglomerados , Viés , Tamanho da Amostra
15.
Molecules ; 28(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36838705

RESUMO

Combretastatin A-4 (CA-4) is a potent tubulin polymerisation inhibitor. However, the clinical application of CA-4 is limited owing to its low aqueous solubility and the easy conversion of the olefin double bond from the more active cis- to the less active trans-configuration. Several structural modifications were investigated to improve the solubility of CA-4 derivatives. Among the compounds we synthesized, the kinetic solubility assay revealed that the solubility of compounds containing a piperazine ring increased the most, and the solubility of compounds 12a1, 12a2, 15 and 18 was increased 230-2494 times compared with that of the control compound (Z)-3-(4-aminophenyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (9a). In addition, these synthesised stilbene nitriles had high anticancer cell (AGS, BEL-7402, MCF-7, and HCT-116) selectivity over L-02 and MCF-10A normal cells while maintaining micromolar activity against cancer cells. The most cytotoxic compound is 9a, and the IC50 value is 20 nM against HCT-116 cancer cells. Preliminary studies indicated that compound 12a1 had excellent plasma stability and moderate binding to rat plasma proteins, suggesting it is a promising lead compound for the development of an anticancer agent.


Assuntos
Antineoplásicos , Estilbenos , Antineoplásicos/farmacologia , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Solubilidade , Estilbenos/química , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia , Humanos , Linhagem Celular Tumoral
16.
Microvasc Res ; 142: 104362, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35337818

RESUMO

During myocardial ischemia, timely reperfusion is critical to limit infarct area and the overall loss of cardiac contractile function. New treatment strategies need to be developed for patients who are neither able to receive interventional treatment nor suitable for surgical blood transport reconstruction surgery. Therapeutic angiogenesis is a promising approach that can be used to guide new treatment strategies. The goal of these therapies is to form new blood vessels or promote the maturation of existing vasculature systems, bypassing blocked arteries to maintain organ perfusion, thereby relieving symptoms and preventing the remodeling of bad organs. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), have been attracted much attention for their roles in various physiological and pathological processes. There is growing evidence that ncRNAs, especially circRNAs, play an important role in the regulation of cardiomyopathy angiogenesis due to its diversity of functions. Therefore, this article reviews the role and mechanisms of circRNA in myocardial angiogenesis to better understand the role of circRNA in myocardial angiogenesis, which may provide useful insights and new revelations for the research field of identifying diagnostic markers and therapeutic approaches for the treatment of coronary artery disease.


Assuntos
Doença da Artéria Coronariana , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , RNA Circular/genética , RNA Longo não Codificante/genética , RNA não Traduzido/genética
17.
J Sleep Res ; 31(1): e13419, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34131989

RESUMO

As the pace of life accelerates, poor sleep quality has become a common health problem. A wealth of sleep studies based on electroencephalogram (EEG) have found that poor sleep quality has decreased alpha rhythm during night-time sleep. However, whether the EEG rhythm during an afternoon nap has a similar impairment has seldom been investigated. By recruiting 35 subjects for a 90-min nap, we explored the relationship between sleep quality and the alpha rhythm, and the contribution of naps to subjective sleep experience. We found that the power of alpha rhythm in the occipital lobe negatively correlated with sleep quality. However, there was no correlation between the sleep quality at night and the sleep duration of the nap, nor the sleep quality and the proportion of each sleep period of a nap. Our present results indicated that the quality of night-time sleep did not affect the macrostructure of the nap. Interestingly, the negative correlation between the alpha rhythm of a nap and sleep quality at night continuously existed in Wake, N1 sleep, and N2 sleep, and had the most substantial value during N2 sleep of a nap. This implies that an impaired occipital lobe alpha rhythm is a robust biomarker for poor sleep. The research is of particular significance for developing electrical neural stimulation therapy to improve sleep quality, especially for the stimuli regions for selection and the time windows for implementation.


Assuntos
Ritmo alfa , Qualidade do Sono , Ritmo Circadiano , Eletroencefalografia , Humanos , Polissonografia , Sono , Vigília
18.
Stat Med ; 41(14): 2645-2664, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35288959

RESUMO

The marginal Fine-Gray proportional subdistribution hazards model is a popular approach to directly study the association between covariates and the cumulative incidence function with clustered competing risks data, which often arise in multicenter randomized trials or multilevel observational studies. To account for the within-cluster correlations between failure times, the uncertainty of the regression parameters estimators is quantified by the robust sandwich variance estimator, which may have unsatisfactory performance with a limited number of clusters. To overcome this limitation, we propose four bias-corrected variance estimators to reduce the negative bias of the usual sandwich variance estimator, extending the bias-correction techniques from generalized estimating equations with noncensored exponential family outcomes to clustered competing risks outcomes. We further compare their finite-sample operating characteristics through simulations and two real data examples. In particular, we found the Mancl and DeRouen (MD) type sandwich variance estimator generally has the smallest bias. Furthermore, with a small number of clusters, the Wald t -confidence interval with the MD sandwich variance estimator carries close to nominal coverage for the cluster-level effect parameter. The t -confidence intervals based on the sandwich variance estimator with any one of the three types of multiplicative bias correction or the z -confidence interval with the Morel, Bokossa and Neerchal (MBN) type sandwich variance estimator have close to nominal coverage for the individual-level effect parameter. Finally, we develop a user-friendly R package crrcbcv implementing the proposed sandwich variance estimators to assist practical applications.


Assuntos
Viés , Simulação por Computador , Humanos , Modelos de Riscos Proporcionais
19.
Neural Plast ; 2022: 1460326, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309255

RESUMO

The analysis of structural covariance has emerged as a powerful tool to explore the morphometric correlations among broadly distributed brain regions. However, little is known about the interactions between the damaged primary motor cortex (M1) and other brain regions in stroke patients with motor deficits. This study is aimed at investigating the structural covariance pattern of the ipsilesional M1 in chronic subcortical stroke patients with motor deficits. High-resolution T1-weighted brain images were acquired from 58 chronic subcortical stroke patients with motor deficits (29 with left-sided lesions and 29 with right-sided lesions) and 50 healthy controls. Structural covariance patterns were identified by a seed-based structural covariance method based on gray matter (GM) volume. Group comparisons between stroke patients (left-sided or right-sided groups) and healthy controls were determined by a permutation test. The association between alterations in the regional GM volume and motor recovery after stroke was investigated by a multivariate regression approach. Structural covariance analysis revealed an extensive increase in the structural interactions between the ipsilesional M1 and other brain regions in stroke patients, involving not only motor-related brain regions but also non-motor-related brain regions. We also identified a slightly different pattern of structural covariance between the left-sided stroke group and the right-sided stroke group, thus indicating a lesion-side effect of cortical reorganization after stroke. Moreover, alterations in the GM volume of structural covariance brain regions were significantly correlated to the motor function scores in stroke patients. These findings indicated that the structural covariance patterns of the ipsilesional M1 in chronic subcortical stroke patients were induced by motor-related plasticity. Our findings may help us to better understand the neurobiological mechanisms of motor impairment and recovery in patients with subcortical stroke from different perspectives.


Assuntos
Córtex Motor , Acidente Vascular Cerebral , Encéfalo , Humanos , Imageamento por Ressonância Magnética/métodos
20.
Korean J Parasitol ; 60(6): 419-421, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36588419

RESUMO

To improve our understanding of the migration of sparganum in humans, we report a case of ocular sparganosis having the migratory episode from the muscle cone to the subconjunctiva. A 34-year-old woman was admitted to the Hospital of Anhui Medical University (Hefei, China), in December 2019. She presented with conjunctival hemorrhage and recurrent pain in the left eye. A foreign body was found in the muscle cone of the eye. Two months later, a ribbon-like white material was found under the conjunctiva on slit-lamp examination. A long and slender, actively moving parasite was extracted by surgery. The extracted worm was approximately 8 cm long and 2 mm wide. The worm was whitish, wrinkled, ribbon shaped, and had a slightly enlarged scolex. The worm sample was morphologically identified as a plerocercoid larva (sparganum) of the Spirometra tapeworm. Her conjunctival blood suffusion and eye pain ceased within 1 week after operation. She has been in good health without any symptoms during the 2-year follow-up. A case of ocular sparganosis, in which larval worm migrated from the muscle cone to the subconjunctiva is reported from China.


Assuntos
Cestoides , Oftalmopatias , Esparganose , Spirometra , Humanos , Animais , Feminino , Adulto , Esparganose/diagnóstico , Esparganose/cirurgia , Esparganose/parasitologia , Plerocercoide , Músculos , China , Larva
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