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1.
Theranostics ; 14(13): 5102-5122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267784

RESUMO

Rationale: Extrachromosomal circular DNA is a hallmark of cancer, but its role in shaping the genome heterogeneity of urothelial bladder carcinoma (UBC) remains poorly understood. Here, we comprehensively analyzed the features of extrachromosomal circular DNA in 80 UBC patients. Methods: We performed whole-genome/exome sequencing (WGS/WES), Circle-Seq, single-molecule real-time (SMRT) long-read sequencing of circular DNA, and RNA sequencing (RNA-Seq) on 80 pairs of tumor and AT samples. We used our newly developed circular DNA analysis software, Circle-Map++ to detect small extrachromosomal circular DNA from Circle-Seq data. Results: We observed a high load and significant heterogeneity of extrachromosomal circular DNAs in UBC, including numerous single-locus and complex chimeric circular DNAs originating from different chromosomes. This includes highly chimeric circular DNAs carrying seven oncogenes and circles from nine chromosomes. We also found that large tumor-specific extrachromosomal circular DNAs could influence genome-wide gene expression, and are detectable in time-matched urinary sediments. Additionally, we found that the extrachromosomal circular DNA correlates with hypermutation, copy number variation, oncogene amplification, and clinical outcome. Conclusions: Overall, our study provides a comprehensive extrachromosomal circular DNA map of UBC, along with valuable data resources and bioinformatics tools for future cancer and extrachromosomal circular DNA research.


Assuntos
Variações do Número de Cópias de DNA , DNA Circular , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/genética , Humanos , DNA Circular/genética , Variações do Número de Cópias de DNA/genética , Sequenciamento Completo do Genoma/métodos , Heterogeneidade Genética , Masculino , Feminino , Sequenciamento do Exoma/métodos , Idoso , Mutação/genética
2.
Front Mol Biosci ; 11: 1399679, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38831933

RESUMO

Background: Gastric cancer is a highly prevalent malignant neoplasm. Metabolic reprogramming is intricately linked to both tumorigenesis and cancer immune evasion. The advent of single-cell RNA sequencing technology provides a novel perspective for evaluating cellular metabolism. This study aims to comprehensively investigate the metabolic pathways of various cell types in tumor and normal samples at high resolution and delve into the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer. Methods: Utilizing single-cell RNA sequencing data from gastric cancer, we constructed metabolic landscape maps for different cell types in tumor and normal samples. Employing unsupervised clustering, we categorized malignant cells in tumor samples into high and low metabolic subclusters and further explored the characteristics of these subclusters. Results: Our research findings indicate that epithelial cells in tumor samples exhibit significantly higher activity in most KEGG metabolic pathways compared to other cell types. Unsupervised clustering, based on the scores of metabolic pathways, classified malignant cells into high and low metabolic subclusters. In the high metabolic subcluster, it demonstrated the potential to induce a stronger immune response, correlating with a relatively favorable prognosis. In the low metabolic subcluster, a subset of cells resembling cancer stem cells (CSCs) was identified, and its prognosis was less favorable. Furthermore, a set of risk genes associated with this subcluster was discovered. Conclusion: This study reveals the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer, offering new perspectives for improving prognosis and treatment strategies.

3.
Childs Nerv Syst ; 40(5): 1623-1630, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38349526

RESUMO

BACKGROUND: Spinal meningiomas coexisting with schwannomas in patients without neurofibromatosis are extremely rare lesions. There were only 15 cases reported to date, which were concurrent intradural tumors of different pathological types. CASE PRESENTATION: Herein, we present a rare case of a 15-year-old child with concurrent spinal dorsal meningioma and ventral giant invasive schwannoma at C7-T3 and T10-S5 spinal levels. Preoperative magnetic resonance imaging and computed tomography indicated the schwannoma across the thoracic and lumbosacral transitional vertebra, with extensive bony erosion of the sacrum. The results of surgical resection were mostly satisfactory. CONCLUSIONS: The present case is the youngest patient diagnosed with concurrent intradural tumors at different spinal levels. The pathogenetic mechanism remains unclear. The clinical presentations are always atypical. Surgical resection of the tumors is the first choice. We use the non-fusion surgery to preserve the function of the lumbar spine.


Assuntos
Neoplasias Meníngeas , Meningioma , Neurilemoma , Neurofibromatoses , Neoplasias da Coluna Vertebral , Adolescente , Humanos , Neoplasias Meníngeas/complicações , Meningioma/cirurgia , Neurilemoma/patologia , Neurofibromatoses/complicações , Neoplasias da Coluna Vertebral/cirurgia
4.
Clin Neurol Neurosurg ; 234: 108008, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37866210

RESUMO

OBJECTIVE: To explore the effect of stereotactic aspiration surgery and conventional treatment for primary brainstem haemorrhage. METHODS: The clinical data of 137 patients with primary brain stem haemorrhage (haematoma volume > 3 ml) from August 2014 to August 2022 at the First Hospital of Hebei Medical University were reviewed. Sixty-five patients were treated with stereotactic haematoma aspiration, and 72 patients were treated with conventional therapy. We followed up on patient survival after 30 days and the recovery of neurological function after 90 days. The recovery of neurological function was evaluated by the modified Rankin Scale (mRS) 90 days after treatment. The mortality and neurological recovery rates of the two treatments were compared and analysed. RESULTS: There was a significant difference in the 30-day mortality rate between the two treatment groups (p < 0.05). There was a significant difference in neurological function improvement after 90 days between the two treatment groups (P < 0.05). There was no significant difference between stereotactic aspiration and routine treatment in the prognosis of primary brainstem haemorrhage patients at 90 days after treatment (P > 0.05). CONCLUSION: Stereotactic aspiration surgery for primary brain stem haemorrhage can significantly reduce mortality and improve the neurological function of some patients.


Assuntos
Hemorragia Cerebral , Hematoma , Humanos , Resultado do Tratamento , Hemorragia Cerebral/cirurgia , Tronco Encefálico/cirurgia
5.
BMC Musculoskelet Disord ; 24(1): 679, 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37633880

RESUMO

BACKGROUND: Low back pain (LBP) is one of the leading causes of disability worldwide. Differences in social backgrounds and lifestyles in various regions and countries may contribute to the discrepancies in the disease burden of LBP. METHODS: Based on the GBD 2019, we collected and analyzed numbers and age-standardized rates (ASR) of LBP disability-adjusted life years (DALYs). Temporal trends in ASR were also analyzed using estimated annual percentage change (EAPC). The Age-period-cohort (APC) model was used to estimate age, period and cohort trends in DALYs of LBP. An autoregressive integrated moving average (ARIMA) model was used to forecast DALYs of LBP trends from 2020 to 2035. RESULTS: The DALYs due to LBP increased from 1990 to 2019. The APC model showed that the risk of DALYs for global LBP increased with age and year and that the risk of DALYs was lower in the later-born cohort than in the earlier-born cohort. The main risk factors which GBD estimates were available for DALYs of LBP include smoking, occupational ergonomic factors and high BMI. It is expected that DALYs of LBP will continue to rise until 2035. CONCLUSION: From 1990 to 2019, the global disease burden of LBP remained high. It is necessary to pay attention to the influence of social factors and lifestyle on LBP. Focusing on the impact of social factors as well as lifestyle on the prognosis of LBP and targeting interventions may further reduce the disease burden of LBP.


Assuntos
Carga Global da Doença , Dor Lombar , Humanos , Fatores Sociais , Dor Lombar/diagnóstico , Dor Lombar/epidemiologia , Efeitos Psicossociais da Doença , Estilo de Vida
6.
J Biol Chem ; 299(9): 105151, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37567479

RESUMO

Hepatitis B virus (HBV) is a hepatotropic DNA virus that has a very compact genome. Due to this genomic density, several distinct mechanisms are used to facilitate the viral life cycle. Recently, accumulating evidence show that G-quadruplex (G4) in different viruses play essential regulatory roles in key steps of the viral life cycle. Although G4 structures in the HBV genome have been reported, their function in HBV replication remains elusive. In this study, we treated an HBV replication-competent cell line and HBV-infected cells with the G4 structure stabilizer pyridostatin (PDS) and evaluated different HBV replication markers to better understand the role played by the G4. In both models, we found PDS had no effect on viral precore RNA (pcRNA) or pre-genomic RNA (pgRNA), but treatment did increase HBeAg/HBc ELISA reads and intracellular levels of viral core/capsid protein (HBc) in a dose-dependent manner, suggesting post-transcriptional regulation. To further dissect the mechanism of G4 involvement, we used in vitro-synthesized HBV pcRNA and pgRNA. Interestingly, we found PDS treatment only enhanced HBc expression from pgRNA but not HBeAg expression from pcRNA. Our bioinformatic analysis and CD spectroscopy revealed that pgRNA harbors a conserved G4 structure. Finally, we introduced point mutations in pgRNA to disrupt its G4 structure and observed the resulting mutant failed to respond to PDS treatment and decreased HBc level in in vitro translation assay. Taken together, our data demonstrate that HBV pgRNA contains a G4 structure that plays a vital role in the regulation of viral mRNA translation.


Assuntos
Quadruplex G , Vírus da Hepatite B , Hepatite B , Humanos , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Hepatite B/virologia , Antígenos E da Hepatite B/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Proteínas do Core Viral/química , Proteínas do Core Viral/metabolismo , Replicação Viral/genética , Linhagem Celular , Quadruplex G/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/genética , Mutação , Aminoquinolinas/farmacologia
7.
Stroke Vasc Neurol ; 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612055

RESUMO

BACKGROUND: At present, neurointerventional surgery requires angiographers to perform operations in the digital subtraction angiography (DSA) room. Ionising radiation and chronic joint damage are still unavoidable for angiographers. Therefore, we researched and developed a neurointerventional robot-assisted system, which is operated by angiographers in an operating room outside the DSA room. We have conducted a prospective, multicentre, randomised controlled trial to evaluate the safety and efficacy of a robot-assisted system in human cerebral angiography. In the future, this research will provide a platform for the research and development of an intelligent surgical system and bring revolutionary progress in neurointerventional surgery. METHODS: From December 2020 to December 2021, 260 patients were enrolled from three medical centres, who were randomly and equally divided into a robot-assisted system group and a clinical routine cerebral angiography group. The success rate of angiography, the rate of the catheter reaching the target vessel, the operation time, X-ray radiation exposure and the incidence of related adverse events were compared between the two groups. RESULTS: A total of 257 patients completed this trial; baseline characteristics of the two groups did not differ significantly. The success rate of angiography in both the control group and the experimental group was 100%. The rate of the catheter reaching the target vessel was 99.23% and 100.00% in the control and experimental groups, respectively. For the control versus experimental groups, the angiographic operation time was 48.59±25.60 min versus 47.94±27.49 min, respectively; the X-ray radiation dose was 735.01±554.77 mGy versus 821.65±705.45 mGy, respectively; and the incidence of adverse events was 23.44% versus 22.48%, respectively. No statistical differences were present between the two groups. CONCLUSION: The robot-assisted surgical system is more convenient for cerebral angiography and is as safe and effective as the traditional cerebral angiography.

8.
Nature ; 621(7979): 610-619, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37557913

RESUMO

The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)3 and the transcription regulator Integrator-PP2A (INTAC)4-6. Through SSB1-mediated recognition of single-stranded DNA, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS-INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2 (encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS-INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.


Assuntos
Instabilidade Genômica , Regiões Promotoras Genéticas , Estruturas R-Loop , Terminação da Transcrição Genética , Humanos , DNA de Cadeia Simples/metabolismo , Instabilidade Genômica/genética , Mutação , Estruturas R-Loop/genética , RNA Polimerase II/metabolismo , Regiões Promotoras Genéticas/genética , Genoma Humano , Proteínas de Ligação a DNA/metabolismo
9.
Front Oncol ; 13: 1152209, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37456232

RESUMO

Background: The global cancer burden is substantial and spiraling. Although rehabilitation specialists could offer assistance, oncologic rehabilitation is still underutilized and not a routine part of clinical oncology guidelines worldwide. Global investigations of disease prevalence and years lived with disability (YLDs) for tracheal, bronchus, and lung (TBL) cancer are valuable for facilitating clinical practice improvement and health resource management. The objective of this study is to report the global estimates of rehabilitation needs and disease burden of TBL cancers from 1990 to 2019 and provide predictions for 2045. Methods: To estimate the need for rehabilitation, the data used from the Global Burden of Disease Study 2019 to calculate the prevalence, YLDs, and the attributable risk factors of TBL cancer. The Bayesian age-period-cohort model and Auto-Regressive Integrated Moving Average model were established to forecast the future health burden. All analyses were done at the global level and then some in the aggregation with the seven World Bank regions. All the data were analyzed by R software (x64 version 4.2.1) and Microsoft Excel (version 2019). Results: Globally in 2019, 3,212,307 cases of TBL cancer (95% UI 2,937,037-3,488,346) could have benefitted from rehabilitation, contributing to 544,215 (95% UI 396,134-700,099) YLDs. Over the past 30 years, the age-standardized rate (ASR) of prevalence (EAPC = 0.51) and YLDs (EAPC = 0.03) increased. Throughout this period, the global prevalence and YLDs counts were greater in males than females. The ASR of prevalence and YLDs are projected to show a slight downward trend by 2045 on the global scale, the overall prevalence and YLDs due to TBL cancer are likely to increase further, but all indicators show a growing trend in females. Conclusion: TBL cancer remains one of the major public health issues globally. According to the forecasted results, the burden of YLDs due to TBL cancer will continue to rise, and the increment is higher in females than males. A rising number of patients worldwide will benefit from rehabilitation services in the future to achieve precise control and management throughout the TBL cancer patient lifecycle.

10.
Support Care Cancer ; 31(3): 161, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36781549

RESUMO

OBJECTIVES: To discuss the effects of physical activity on cancer-related fatigue (CRF) in lung cancer patients, summarize the types of physical activity in the published reviews, assess the quality of the evidence, and provide suggestions for the clinical selection of exercise intervention. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews were searched through 8 November 2021 to identify relevant systematic reviews and meta-analyses. We also performed a manual search of the reference lists of included articles as supplements. Two researchers independently performed literature screening, data extraction, and quality assessment. The umbrella review has been registered in the International Prospective Register of Systematic Review (PROSPERO) registry (CRD42021292548). RESULTS: From the 13 systematic reviews or meta-analyses identified, 10 physical activity interventions were included. The most mentioned intervention was aerobic combined with resistance exercise; however, no reduction of the symptoms of CRF was observed in lung cancer patients by this exercise intervention. Most of the patients who performed aerobic exercises alone showed improvement in CRF after the intervention. In addition, Tai Chi and breathing exercises have been shown to improve fatigue, but more high-quality research is still needed to support its effectiveness. CONCLUSIONS: Aerobic exercise, respiratory muscle training, aerobic combined with balance training, and other exercise interventions have been shown to improve CRF in lung cancer patients. But it should be noted that according to the different treatment methods and disease stages of patients, individualized rehabilitation programs should be developed for patients. Due to the low methodological quality and evidence quality of some systematic reviews and meta-analyses included in this study, more high-quality clinical studies and systematic reviews are still needed for validation in the future. This umbrella review helps to identify effective ways of exercise to improve fatigue in lung cancer patients before dedicated evidence-based medical guidelines are established.


Assuntos
Exercício Físico , Neoplasias Pulmonares , Humanos , Revisões Sistemáticas como Assunto , Exercício Físico/fisiologia , Neoplasias Pulmonares/complicações , Fadiga/etiologia , Fadiga/terapia , Terapia por Exercício/métodos , Qualidade de Vida
11.
Support Care Cancer ; 31(1): 97, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36598576

RESUMO

PURPOSE: There has been growing amount of evidence supporting the benefits of physical activity (PA) on oncological patients' cancer-related health outcomes. Although guidelines on cancer rehabilitation are widely available, the varying quality and practical applicability limited the clinical application of PA recommendations. To assist the future development of guidelines, in this systematic review, we evaluated the quality and applicability of current cancer rehabilitation guidelines with PA recommendations and synthesized PA recommendations for the oncological population. METHODS: A systematic search was conducted in PubMed, CINAHL, PEDro, EMBASE, and guideline repositories to identify guidelines with PA recommendations for cancer patients from 1 May 2016 to 1 June 2022. The quality of included guidelines was appraised using the tools "Appraisal of Guidelines for Research and Evaluation II" (AGREE II) and AGREE-REX (Recommendation Excellence). PA recommendations were synthesized from the guidelines. RESULTS: Sixteen guidelines were extracted. The AGREE II domain "clarity of presentation" obtained the highest score, while "applicability" received the lowest, ranging from 33.33% to 98.58%. The AGREE-REX domains "values and preferences" and "implementability" generally scored lower and ranged from 45.83% to 74.17% and 55% to 88.33%, respectively. Eight high-quality guidelines were identified, and the included PA recommendations were extracted. CONCLUSION: There were some disparities in the quality of the included guidelines. Methodological weaknesses were commonly observed in domains "applicability," "values and preferences," and "implementability"; particular attention should be given to these domains when developing future guidelines. Furthermore, this analysis indicated that more rigorous, high-quality studies are needed to generate evidence for supporting PA recommendations and provide guidance on research gaps in the field of cancer rehabilitation.


Assuntos
Neoplasias , Humanos , Neoplasias/terapia , Exercício Físico , Oncologia
12.
Int J Mol Sci ; 23(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36555782

RESUMO

Phellinus baumii, a fungus that grows on mulberry trees and is used in traditional Chinese medicine, exerts therapeutic effects against various diseases, including cancer. Polyphenols, generally considered to be antioxidants, have antitumor and proapoptotic effects. In this study, we identified the composition of Phellinus baumii polyphenol (PBP) and characterized its 17 chemical components by UPLC-ESI-QTOF-MS. Furthermore, to clarify the potential mechanism of PBP against Lung Cancer Cells, network pharmacology and experimental verification were combined. Molecular docking elucidated the binding conformation and mechanism of the primary active components (Osmundacetone and hispidin) to the core targets CASP3, PARP1 and TP53. In addition, potential molecular mechanisms of PBP predicted by network pharmacology analysis were validated in vitro. PBP significantly inhibited the human lung cancer A549 cells and showed typical apoptotic characteristics, without significant cytotoxicity to normal human embryonic kidney (HEK293) cells. Analysis using flow cytometry and western blot indicated that PBP caused apoptosis, cell cycle arrest, reactive oxygen species (ROS) accumulation, and mitochondrial membrane potential (MMP) depression in A549 cells to exercise its antitumor effects. These results reveal that PBP has great potential for use as an active ingredient for antitumor therapy.


Assuntos
Neoplasias Pulmonares , Polifenóis , Humanos , Polifenóis/farmacologia , Polifenóis/química , Simulação de Acoplamento Molecular , Células HEK293 , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Apoptose
14.
Front Surg ; 9: 945905, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061043

RESUMO

Purpose: Brainstem hemorrhage is usually treated conservatively with medication and has high mortality and morbidity rates. Stereotactic aspiration can directly and microinvasively draw out the hemorrhage within a narrow space in the brainstem, thus promoting quick recovery and potentially saving the life of the patient. This study was conducted to investigate the effect of stereotactic aspiration on patients with brainstem hemorrhage in a case series. Materials and methods: A total of 42 patients with brainstem hemorrhage were enrolled for stereotactic aspiration of the brain hemorrhage, and another 30 patients with brainstem hemorrhage were enrolled for conservative treatment. The clinical and imaging data were analyzed and compared. Results: Stereotactic aspiration was successful in all patients (100%), with immediate elimination of hematoma in the brainstem. In five patients with the hemorrhage extending to the fourth ventricle (n = 1) and basal ganglia (n = 4), the hemorrhage was eliminated, resulting in good outcomes. However, four patients died of multiple organ failure after aspiration, resulting in a mortality rate of 9.5%. One week after surgery, the Glasgow Coma Scale (GCS) score ranged from 3 to 11 (mean 5.9 ± 2.3). At 1-month follow-up, 4 patients died, and 36 patients survived, with the GCS score ranging between 3 and 15 (mean 8.6 ± 2.1), which was significantly (P < 0.01) higher than that before surgery. The Modified Rankin Scale (mRS) score was 5 before treatment, 5 (4.4, 6) at 1 week after surgery, and 5 (4, 6) at 1 month. In the conservative group, 16 (53.3%) patients died during hospitalization. The GCS score was 0-6 (mean 2.3 ± 1.1), which was significantly (P < 0.05) worse than at admission or of that in the aspiration group at 1 month. The mRS score at 1 month was 6 (5, 6), which was significantly (P < 0.05) worse than that in the aspiration group. Conclusion: Stereotactic aspiration for brainstem hemorrhage as an approach of microinvasiveness may be effective in evacuating brainstem hemorrhage and may promote quick recovery of the patient, resulting in better clinical outcomes.

15.
Sci Rep ; 12(1): 14039, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35982096

RESUMO

Aiming at solving the effective data delivery and energy hole problem in multi-hop cognitive radio sensor networks (CRSNs), a weighted energy consumption minimization-based uneven clustering (ECMUC) routing protocol is proposed in this paper. For the first time, the impact of control overhead on the network performance is taken into consideration, to be specific, the energy consumption of control overhead is integrated with that of data communication to model the network energy consumption. Through effective transformation and theoretical analysis, cluster radius of each ring is derived by minimizing the network energy consumption and balancing the residual energy among nodes in different rings. Distributed cluster heads (CHs) selection and cluster formation are carried out within this range to control the cluster size and the corresponding energy cost. Expected times for being CHs metric is defined to measure nodes' energy and spectral potential and help select powerful CHs. Simulation results show that ECMUC protocol is superior to most clustering protocols designed for CRSNs in terms of network surveillance capability and network lifetime, and it is also demonstrated that taking control overhead into consideration is beneficial for improving the network performance.

16.
Methods Mol Biol ; 2528: 345-357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35704203

RESUMO

R-loops are three-stranded nucleic acid structures that consist of a DNA-RNA hybrid and a displaced single-stranded DNA. R-loops occur during transcription and participate in multiple physiological processes such as DNA repair, modulating DNA topology, and regulation of gene transcription. Dysfunctional R-loops associate with several human diseases such as neurological disorders and cancer. Therefore, accurately and comprehensively profiling native R-loops is crucial to understand their functions under both physiological and pathological conditions. Here, we describe a convenient native R-loop profiling method, R-loop CUT&Tag, which combines a DNA-RNA hybrid sensor (GST-His6-2 × HBD or S9.6 antibody) with a pA-Tn5-based cleavage under targets and tagmentation approach. R-loop CUT&Tag starts with 0.5 million cells and can sensitively detect native and specific R-loops at the promoter, gene body, and enhancer regions.


Assuntos
Estruturas R-Loop , RNA , DNA/genética , Reparo do DNA , DNA de Cadeia Simples/genética , Humanos , Estruturas R-Loop/genética , RNA/genética
17.
Brain Sci ; 12(6)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35741642

RESUMO

Objectives: our group explored the correlation between postoperative coordinates of the electrode contacts, VTA, and anxiety and depression symptoms in Parkinson's disease (PD) patients after subthalamic nucleus deep brain stimulation (STN-DBS). Methods: STN-DBS was conducted on PD patients (n = 57) for six months with follow-up. Clinical outcomes were explored using the unified Parkinson's disease rating scale Part III (UPDRS-III), the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D) before and after surgery. At the Montreal Neurological Institute (MNI), the location of active contacts and the volume of tissue activated (VTA) were calculated. Results: patient evaluations took place preoperatively and follow-ups took place at 1 month, 3 months, and 6 months. The average patient improvement rates for HAM-A and HAM-D scores at the 6-month follow-up were 41.7% [interquartile range (IQR) 34.9%] and 37.5% (IQR 33.4%), respectively (both p < 0.001). In medication-off, there were negative correlations between the HAM-A improvement rate and the Z-axis coordinate of the active contact (left side: r = −0.308, p = 0.020; right side: r = −0.390, p = 0.003), and negative correlations between the HAM-D improvement rate and the Z-axis coordinate of the active contact (left side: r = −0.345, p = 0.009; right side: r = −0.521, p = 0.001). There were positive correlations between the HAM-A and HAM-D scores improvement rate at 6 months after surgery and bilateral VTA in the right STN limbic subregion (HAM-A: r = 0.314, p = 0.018; HAM-D: r = 0.321, p = 0.015). Conclusion: bilateral STN-DBS can improve anxiety and depression symptoms in PD patients. The closer the stimulation to the ventral limbic region of the STN, the more significant the improvement in anxiety and depression symptoms of PD patients.

18.
Mol Med ; 28(1): 50, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508991

RESUMO

BACKGROUND: The conversion of astrocytes activated by nerve injuries to oligodendrocytes is not only beneficial to axonal remyelination, but also helpful for reversal of glial scar. Recent studies have shown that pathological niche promoted the Sox10-mediated astrocytic transdifferentiation to oligodendrocytes. The extracellular factors underlying the cell fate switching are not known. METHODS: Astrocytes were obtained from mouse spinal cord dissociation culture and purified by differential adherent properties. The lineage conversion of astrocytes into oligodendrocyte lineage cells was carried out by Sox10-expressing virus infection both in vitro and in vivo, meanwhile, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) inhibitor Gefitinib were adopted to investigate the function of EGF signaling in this fate transition process. Pharmacological inhibition analyses were performed to examine the pathway connecting the EGF with the expression of oligodendrogenic genes and cell fate transdifferentiation. RESULTS: EGF treatment facilitated the Sox10-induced transformation of astrocytes to O4+ induced oligodendrocyte precursor cells (iOPCs) in vitro. The transdifferentiation of astrocytes to iOPCs went through two distinct but interconnected processes: (1) dedifferentiation of astrocytes to astrocyte precursor cells (APCs); (2) transformation of APCs to iOPCs, EGF signaling was involved in both processes. And EGF triggered astrocytes to express oligodendrogenic genes Olig1 and Olig2 by activating extracellular signal-regulated kinase 1 and 2 (Erk1/2) pathway. In addition, we discovered that EGF can enhance astrocyte transdifferentiation in injured spinal cord tissues. CONCLUSIONS: These findings provide strong evidence that EGF facilitates the transdifferentiation of astrocytes to oligodendrocytes, and suggest that targeting the EGF-EGFR-Erk1/2 signaling axis may represent a novel therapeutic strategy for myelin repair in injured central nervous system (CNS) tissues.


Assuntos
Astrócitos , Fator de Crescimento Epidérmico , Animais , Astrócitos/metabolismo , Diferenciação Celular , Células Cultivadas , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/metabolismo , Camundongos , Oligodendroglia/metabolismo
19.
BMC Neurol ; 22(1): 124, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361123

RESUMO

BACKGROUND: To study the effects of subthalamic nucleus-deep brain stimulation (STN-DBS) on autonomic dysfunctions in Parkinson's disease (PD) patients. METHODS: A total of 57 PD patients who underwent bilateral STN-DBS from March to December 2018, were retrospectively analyzed. Preplanned assessments at baseline and postoperatively at 1, 3, and 6 months also included the Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-Aut), the Unified Parkinson's Disease Rating Scale (UPDRS) III score, levodopa equivalent day dose (LEDD), Parkinson's Disease Quality of Life Scale (PDQ-39), the Hamilton Anxiety Rating Scale (HAMA), and the Hamilton Depression Rating Scale (HAMD). RESULTS: The SCOPA-Aut scores improved significantly [14.59% (18.32%), 24.00% (27.05%), 22.16% (27.07%), all P < 0.001] at 1 month, 3 months, and 6 months of STN-DBS, respectively. Analysis of the SCOPA-Aut sub-items showed significant improvements only in urine and thermoregulation sub-items at 6 months after surgery (P < 0.001). There was no significant correlation between improvements of SCOPA-Aut scores and improvements of PDQ-39 scores (P > 0.05) at 6 months after surgery. SCOPA-Aut scores were positively correlated with age (r = 0.428, P = 0.001); the improvements of SCCOPA-Aut scores were positively correlated with improvements of HAMA and HAMD scores (HAMA: r = 0.325, P = 0.015; HAMD: r = 0.265, P = 0.049) at 6 months after surgery. CONCLUSION: STN-DBS improved autonomic dysfunction symptoms of PD patients, and urinary and thermoregulatory sub-items of autonomic dysfunction were improved in the short-term after surgery. There was a close relationship between improved autonomic symptoms and improved anxiety and depression 6 months after surgery. We should therefore direct more attention to autonomic dysfunctions in PD involving detailed preoperative evaluations and postoperative follow-ups, to improve the quality of life of patients.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Disautonomias Primárias , Núcleo Subtalâmico , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Qualidade de Vida , Estudos Retrospectivos , Núcleo Subtalâmico/fisiologia , Núcleo Subtalâmico/cirurgia
20.
J Neurol Surg A Cent Eur Neurosurg ; 83(3): 265-274, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34788868

RESUMO

PURPOSE: The purpose of the study was to investigate the safety and efficacy of endovascular embolization of ruptured intracranial aneurysms within 72 hours of subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Patients with intracranial aneurysms treated with embolization were divided into group A (n = 277), patients with ruptured aneurysms treated within 72 hours of SAH; group B (n = 138), patients with ruptured aneurysms treated beyond 72 hours; and group C (n = 93), patients with unruptured aneurysms. RESULTS: Embolization was successful in all but four patients (99.2%). The periprocedural complication rate was 36.2% in group B, significantly (p < 0.05) greater than that in group A (24.5%) or group C (11.8%). The rebleeding rate was 9.7% (6/62 patients) in groups A and B after embolization and only 0.3% (1/346 patients) in aneurysms with total or subtotal occlusion. Of these three groups of patients, 69.7% in group A, 58.7% in group B, and 76.3% in group C achieved Glasgow Outcome Scale (GOS) score of 5 or modified Rankin Scale (mRS) score of 0- to 1 at discharge. A significant difference (p < 0.05) existed in the clinical outcome between the three groups. The percentages of patients without deficits (GOS 5 or mRS 0-1) and slight disability (mRS 2) were 80.2% in group A, 81.2% in group B, and 96.7% in group C. The mortality rate was 4.3% (12/277 patients) in group A and 7.2% (10/138 patients) in group B with no significant (p = 0.21) difference. Follow-up was performed at 3 to 54 months (mean 23.2), and the recanalization rate was 28.6% (32/112 patients) in group A, 22.4% (11/49 patients) in group B, and 28.6% (16/56 patients) in group C, with no significant differences (p = 0.15). Hydrocephalus occurred in 30.5% (39/128 patients) in group B, which was significantly (p < 0.01) greater than that in group A (9.4%) or group C (2.2%). CONCLUSION: Early embolization of ruptured cerebral aneurysms within 72 hours of rupture is safe and effective and can significantly decrease periprocedural complications compared with management beyond 72 hours. Timely management of cisternal and ventricular blood can reduce hydrocephalus incidence and improve prognosis.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Hidrocefalia , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Embolização Terapêutica/efeitos adversos , Humanos , Hidrocefalia/etiologia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/cirurgia , Resultado do Tratamento
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