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1.
Transl Stroke Res ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302738

RESUMO

Hypertension and aging are leading risk factors for stroke and vascular contributions to cognitive impairment and dementia (VCID). Most animal models fail to capture the complex interplay between these pathophysiological processes. In the current study, we examined the development of cognitive impairment in 18-month-old spontaneously hypertensive rats (SHR) before and following ischemic stroke. Sixty SHRs were housed for 18 months with cognitive assessments every 6 months and post-surgery. MRI scans were performed at baseline and throughout the study. On day 3 post-stroke, rats were randomized to receive either angiotensin II type 2 receptor (AT2R) agonist Compound 21 (C21) or plain water for 8 weeks. SHRs demonstrated a progressive cognitive decline and significant MRI abnormalities before stroke. Perioperative mortality within 72 h of stroke was low. Stroke resulted in significant acute brain swelling, chronic brain atrophy, and sustained sensorimotor and behavioral deficits. There was no evidence of anhedonia at week 8. C21 enhanced sensorimotor recovery and ischemic lesion resolution at week 8. SHRs represent a clinically relevant animal model to study aging and stroke-associated VCID. This study underscores the importance of translational disease modeling and provides evidence that modulation of the AT2R signaling via C21 may be a useful therapeutic option to improve sensorimotor and cognitive outcomes even in aged animals.

2.
Cell Cycle ; 23(1): 56-69, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38389126

RESUMO

AXL plays crucial roles in the tumorigenesis, progression, and drug resistance of neoplasms; however, the mechanisms associated with AXL overexpression in tumors remain largely unknown. In this study, to investigate these molecular mechanisms, wildtype and mutant proteins of arrestin domain-containing protein 3 (ARRDC3) and AXL were expressed, and co-immunoprecipitation analyses were performed. ARRDC3-deficient cells generated using the CRISPR-Cas9 system were treated with different concentrations of the tyrosine kinase inhibitor sunitinib and subjected to cell biological, molecular, and pharmacological experiments. Furthermore, immunohistochemistry was used to analyze the correlation between ARRDC3 and AXL protein expressions in renal cancer tissue specimens. The experimental results demonstrated that ARRDC3 interacts with AXL to promote AXL ubiquitination and degradation, followed by the negative regulation of downstream signaling mechanisms, including the phosphorylation of protein kinase B and extracellular signal-regulated kinase. Notably, ARRDC3 deficiency decreased the sunitinib sensitivity of clear cell renal cell carcinoma (ccRCC) cells in a manner dependent on the regulation of AXL stability. Overall, our results suggest that ARRDC3 is a negative regulator of AXL and can serve as a novel predictor of sunitinib therapeutic response in patients with ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Arrestinas/metabolismo , Arrestinas/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Sunitinibe/farmacologia , Sunitinibe/uso terapêutico
3.
Oper Neurosurg (Hagerstown) ; 26(4): 433-441, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37976445

RESUMO

BACKGROUND AND OBJECTIVE: Microvascular decompression (MVD) is the most definitive and preferred surgical treatment for trigeminal neuralgia (TN). Treatment of TN caused by the vertebrobasilar artery (VBA) has been reported to be challenging and less satisfactory in complications and recurrence. Endoscopy has been implemented to provide a comprehensive view of neurovascular conflicts and minimize brain tissue stretch injury while exploring the trigeminal nerve. However, there are few retrospective studies on the treatment of TN caused by VBA by fully endoscopic microvascular decompression (E-MVD). This article aimed to illustrate the safety and efficacy of E-MVD for TN caused by the VBA. METHODS: Clinical data for 26 patients with TN caused by the VBA who underwent E-MVD from 2019 to 2022 were retrospectively analyzed. The characteristics of vertebrobasilar-associated TN were summarized. The safety and efficacy of E-MVD for vertebrobasilar-associated TN were estimated based on the analysis of intraoperative manipulation, postoperative symptom relief, and complications. RESULTS: Intraoperatively, the vertebrobasilar artery was regarded as a direct offending vessel in all 26 patients with TN, the vertebral artery in 18 (69.23%) and the basilar artery in 10 (38.46%). In addition to the vertebrobasilar artery, other vessels involved included the superior cerebellar artery in 12 patients, anterior inferior cerebellar artery in 9, posterior inferior cerebellar artery in 1, and veins in 4. All patients underwent E-MVD, and TN was entirely resolved in 26 (100%) patients immediately postoperatively. During the follow-up period of 12-45 months, no recurrence or serious complications were found. There were no serious postoperative complications, such as cerebellar swelling, intracranial hemorrhage, or death. CONCLUSION: E-MVD for vertebrobasilar-associated TN is effective and safe.


Assuntos
Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo , Humanos , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/cirurgia , Estudos Retrospectivos , Cirurgia de Descompressão Microvascular/métodos , Artéria Basilar/diagnóstico por imagem , Artéria Basilar/cirurgia , Endoscopia
4.
Front Chem ; 11: 1269911, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38099192

RESUMO

Objective: Although radiation workers are exposed to much lower doses of neutron-γ rays than those suffered in nuclear explosions and accidents, it does not mean that their health is not affected by radiation. Lower doses of radiation do not always cause morphological aberrations in chromosomes, so more sophisticated tests must be sought to specific alterations in the exposed cells. Our goal was to characterize the specific gene expression in lymphocytes from logging workers who were continuously exposed to low doses of neutron-γ radiation. We hypothesized that the combination of cell type-specific transcriptomes and open chromatin profiles would identify lymphocyte-specific gene alterations induced by long-term radiation with low-dose neutron-γ-rays and discover new regulatory pathways and transcriptional regulatory elements. Methods: Lymphocytes were extracted from workers who have been occupationally exposed to neutron-γ and workers unexposed to radiation in the same company. mRNA-seq and ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) were performed, followed integrative analysis to identify specific gene regulatory regions induced by neutron-γ radiation. A qPCR assay was then performed to verify the downregulation of RNA coding for ribosomal proteins and flow cytometry was used to detect ribosomal protein expression and cell cycle alterations. Results: We identified transcripts that were specifically induced by neutron-γ radiation and discovered differential open chromatin regions that correlated with these gene activation patterns. Notably, we observed a downward trend in the expression of both differentially expressed genes and open chromatin peaks. Our most significant finding was that the differential peak upregulated in ATAC-seq, while the differential gene was downregulated in the ribosome pathway. We confirmed that neutron-γ radiation leads to transcriptional inhibition by analyzing the most enriched promoters, examining RPS18 and RPS27A expression by qPCR, and analyzing protein-protein interactions of the differential genes. Ribosomal protein expression and cell cycle were also affected by neutron-γ as detected by flow cytometry. Conclusion: We have comprehensively analyzed the genetic landscape of human lymphocytes based on chromatin accessibility and transcript levels, enabling the identification of novel neutron-γ induced signature genes not previously known. By comparing fine-mapping of open chromatin and RNA reads, we have determined that neutron-γ specifically leads to downregulation of genes in the ribosome pathway, with pseudogenes potentially playing a crucial role.

6.
Biochim Biophys Acta Gene Regul Mech ; 1866(3): 194962, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37499935

RESUMO

Tudor domain-containing protein 3 (TDRD3) is involved in regulating transcription and translation, promoting breast cancer progression, and modulating neurodevelopment and mental health, making it a promising therapeutic target for associated diseases. The Tudor domain of TDRD3 is essential for its biological functions, and targeting this domain with potent and selective chemical probes may modulate its engagement with chromatin and related functions. Here we reported a study of TDRD3 antagonist following on our earlier work on the development of the SMN antagonist, Compound 1, and demonstrated that TDRD3 can bind effectively to Compound 2, a triple-ring analog of Compound 1. Our structural analysis suggested that the triple-ring compound bound better to TDRD3 due to its smaller side chain at Y566 compared to W102 in SMN. We also revealed that adding a small hydrophobic group to the N-methyl site of Compound 1 can improve binding. These findings provide a path for identifying antagonists for single canonical Tudor domain-containing proteins such as TDRD3 and SMN.


Assuntos
Cromatina , Proteínas , Domínio Tudor , Proteínas/química
7.
Radiol Imaging Cancer ; 5(3): e220019, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37233207

RESUMO

Purpose To demonstrate the feasibility of using chemical shift fat-water MRI methods to visualize and measure intrahepatic delivery of ethiodized oil to liver tumors following conventional transarterial chemoembolization (cTACE). Materials and Methods Twenty-eight participants (mean age, 66 years ± 8 [SD]; 22 men) with hepatocellular carcinoma (HCC) treated with cTACE were evaluated with follow-up chemical shift MRI in this Health Insurance Portability and Accountability Act-compliant prospective, institutional review board-approved study. Uptake of ethiodized oil was evaluated at 1-month follow-up chemical shift MRI. Measurements of tumor size (MRI and CT), attenuation and enhancement (CT), fat content percentage, and tumor:normal ratio (MRI) were compared by lesion for responders versus nonresponders, as assessed with modified Response Evaluation Criteria in Solid Tumors and European Association for the Study of the Liver (EASL) criteria. Adverse events and overall survival by the Kaplan-Meier method were secondary end points. Results Focal tumor ethiodized oil retention was 46% (12 of 26 tumors) at 24 hours and 47% (18 of 38 tumors) at 1 month after cTACE. Tumor volume at CT did not differ between EASL-defined responders and nonresponders (P = .06). Tumor ethiodized oil volume measured with chemical shift MRI was statistically significantly higher for EASL-defined nonresponders (P = .02). Doxorubicin dosing (P = .53), presence of focal fat (P = .83), and a combined end point of focal fat and low doxorubicin dosing (P = .97) did not stratify overall survival after cTACE. Conclusion Chemical shift MRI allowed for assessment of tumor delivery of ethiodized oil out to 1 month after cTACE in participants with HCC and demonstrated tumor ethiodized oil volume as a potential tool for stratification of tumor response by EASL criteria. Keywords: MRI, Chemical Shift Imaging, CT, Hepatic Chemoembolization, Ethiodized Oil Clinicaltrials.gov registration no.: NCT02173119 Supplemental material is available for this article. © RSNA, 2023.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Masculino , Humanos , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Óleo Etiodado/efeitos adversos , Estudos de Viabilidade , Estudos Prospectivos , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Doxorrubicina , Imageamento por Ressonância Magnética
8.
BMC Cancer ; 23(1): 259, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36941554

RESUMO

PURPOSE: The combined application of immune checkpoint inhibitors (ICIs) and anti-angiogenesis therapy has shown synergistic effects on glioblastoma (GBM). As important resources of PD-L1 in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) have significant impact of the efficiency of ICIs. However, the effects of anti-angiogenesis agents on immune checkpoints expression are not fully understood. METHOD: GBM-educated macrophages were generated from circulating monocytes of healthy controls and GBM patients under the education of GBM cell line. Surface expression of PD-L1 and VEGFR1 on GBM-educated macrophages was analyzed. VEGFR1 NAb and soluble VEGFR1 (sVEGFR1) were added and their effects on PD-L1 expression on TAMs was investigated. Serum soluble PD-L1 (sPD-L1) and sVEGFR1 levels in GBM patients were measured and their correlation was analyzed. RESULT: The expression intensity of PD-L1 on GBM-educated macrophages was higher and its up-regulation partially depends on VEGFR1 signaling pathway. GBM-educated macrophages secreted less levels of soluble VEGFR1 (sVEGFR1), and exogenous sVEGFR1 down-regulated PD-L1 expression intensity. PD-L1 blockade promoted the secretion of sVEGFR1. Finally, sVEGFR1 and sPD-L1 in serum of GBM patients were overexpressed, and a positive correlation was found. CONCLUSION: These findings reveal the interaction between PD-L1 and VEGFR1 signaling pathway in GBM-educated macrophages. VEGFR1 is involved with PD-L1 overexpression, which can be impeded by autocrine regulation of sVEGFR1. sVEGFR1 secretion by GBM-educated macrophages can be promoted by PD-L1 blockade. Taken together, these findings provide evidences for the combined application of ICIs and anti-angiogenesis therapies in the treatment of GBM.


Assuntos
Antígeno B7-H1 , Glioblastoma , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Humanos , Antígeno B7-H1/metabolismo , Linhagem Celular , Glioblastoma/patologia , Macrófagos/metabolismo , Monócitos/patologia , Microambiente Tumoral , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Front Neurol ; 13: 1061274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36504645

RESUMO

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for the treatment of Parkinson's disease (PD). Moreover, remote programming is widely used in Mainland China. This necessitates evaluating the ability of remote programming to achieve the ideal postoperative effect. Therefore, we aimed to retrospectively evaluate the effects of different programming modes on the effectiveness of STN-DBS 12 months postoperatively in patients with PD. Methods: Clinical data were collected retrospectively, before and 12 months after surgery, in 83 patients with PD. Based on the programming modes voluntarily selected by the patients during 12 months postoperatively, they were divided into three groups, namely remote programming alone, hospital programming alone, and hospital + remote programming. We compared the programming data and the effects of different programming methods on STN-DBS-related improvements 12 months postoperatively among these groups. Furthermore, we analyzed STN-DBS-related improvements at 12 months postoperatively in 76 patients. Results: The effectiveness of STN-DBS was not influenced by the three programming modes. The postoperative Movement Disorder Society Unified Parkinson's Disease Rating Scale scores did not reveal statistically significant differences between the remote alone and hospital alone programming groups, except for motor examination. The postoperative decline in the levodopa equivalent daily dose was most apparent in the hospital programming alone group. The programming frequency of the hospital + remote programming group was considerably higher than that of the remaining groups. Seventy-six patients with PD displayed good STN-DBS surgical efficacy. Conclusion: Programming modes do not influence the short-term efficacy of STN-DBS, and remote programming can yield a satisfactory surgical effect.

12.
Front Oncol ; 12: 940001, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936749

RESUMO

Despite recent advances in cancer research, glioblastoma multiforme (GBM) remains a highly aggressive brain tumor as its treatment options are limited. The current standard treatment includes surgery followed by radiotherapy and adjuvant chemotherapy. However, surgery without image guidance is often challenging to achieve maximal safe resection as it is difficult to precisely discern the lesion to be removed from surrounding brain tissue. In addition, the efficacy of adjuvant chemotherapy is limited by poor penetration of therapeutics through the blood-brain barrier (BBB) into brain tissues, and the lack of tumor targeting. In this regard, we utilized a tumor-targeting cell-penetration peptide, p28, as a therapeutic agent to improve the efficacy of a current chemotherapeutic agent for GBM, and as a carrier for a fluorescence imaging agent for a clear identification of GBM. Here, we show that a near-infrared (NIR) imaging agent, ICG-p28 (a chemical conjugate of an FDA-approved NIR dye, indocyanine green ICG, and tumor-targeting p28 peptide) can preferentially localize tumors in multiple GBM animal models. Moreover, xenograft studies show that p28, as a therapeutic agent, can enhance the cytotoxic activity of temozolomide (TMZ), one of the few effective drugs for brain tumors. Collectively, our findings highlight the important role of the tumor-targeting peptide, which has great potential for intraoperative image-guided surgery and the development of new therapeutic strategies for GBM.

13.
Oper Neurosurg (Hagerstown) ; 23(1): 40-45, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35726928

RESUMO

BACKGROUND: Microvascular decompression (MVD) is widely accepted as the preferred treatment for hemifacial spasm (HFS). Endoscopy has been implemented to provide a comprehensive view of neurovascular conflicts and minimize the damage caused by brain retraction while exploring the facial nerve root exit zone of the brain stem. OBJECTIVE: To preliminarily evaluate the surgical safety and efficacy of fully endoscopic MVD for HFS using an improved retrosigmoid infrafloccular approach. METHODS: The clinical data of 81 patients with HFS who underwent fully endoscopic MVD using an improved endoscopic retrosigmoid infrafloccular approach from June 2019 to December 2020 were retrospectively analyzed. The reliability and advantages of this surgical technique in the treatment of HFS were evaluated according to the intraoperative situation, outcomes of postoperative symptoms, and main complications. RESULTS: During the follow-up period, 77 cases (95.1%) were completely cured, with immediate facial twitch disappearance in 56 cases and a delayed cure in 21 cases; in 4 cases (4.9%), there was no obvious improvement. There were no cases of recurrence. There were 4 cases (4.9%) of transient facial paralysis after MVD, all of which were completely cured in 3 months. Three cases (3.7%) had hearing loss postoperatively, of whom 2 showed good improvement. At the end of the follow-up period, 1 case (1.2%) still had tinnitus. There were no cases of postoperative intracranial hemorrhage, cerebellar swelling, or death. CONCLUSION: Fully endoscopic MVD using an improved retrosigmoid infrafloccular approach not only has the advantages of panoramic surgical visualization but also takes into account the requirements of minimally invasive surgery.


Assuntos
Endoscopia , Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Endoscopia/métodos , Espasmo Hemifacial/cirurgia , Humanos , Cirurgia de Descompressão Microvascular/métodos , Estudos Retrospectivos , Resultado do Tratamento
14.
Front Aging Neurosci ; 14: 771328, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517050

RESUMO

Norrie disease (ND; OMIM 310600), a rare X-linked recessive genetic disorder, is characterized by congenital blindness and occasionally, sensorineural hearing loss, and developmental delay. The congenital blindness of ND patients is almost untreatable; thus, hearing is particularly important for them. However, the mechanism of hearing loss of ND patients is unclear, and no good treatment is available except wearing hearing-aid. Therefore, revealing the mechanism of hearing loss in ND patients and exploring effective treatment methods are greatly important. In addition, as a serious monogenic genetic disease, convenient gene identification method is important for ND patients and their family members, as well as prenatal diagnosis and preimplantation genetic diagnosis to block intergenerational transmission of pathogenic genes. In this study, a Norrie family with two male patients was reported. This pedigree was ND caused by large fragment deletion of NDP (norrin cystine knot growth factor NDP) gene. In addition to typical severe ophthalmologic and audiologic defects, the patients showed new pathological features of endolymphatic hydrops (EH), and they also showed acoustic nerves abnormal as described in a very recent report. PCR methods were developed to analyze and diagnose the variation of the family members. This study expands the understanding of the clinical manifestation and pathogenesis of ND and provides a new idea for the treatment of patients in this family and a convenient method for the genetic screen for this ND family.

15.
Int Immunopharmacol ; 107: 108586, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35228032

RESUMO

Tumor-associated macrophages (TAMs) are major innate immune cells that play crucial roles in prostate cancer onset and progression. Recently, increasing evidence has suggested that elevated N6-adenine methylation of mRNA is observed in prostate cancer tissues and is closely associated with a poor prognosis. However, its role in prostate cancer-associated macrophages remains poorly understood. Here, we showed that downregulation of METTL3 in prostate cancer TAMs modulated macrophages toward an M2-like phenotype and that this modulation was mediated by activation of STAT6. In addition, our data demonstrated that prostate cancer cell-derived small lipid molecule lipoxin A4 (LXA4) activated STAT6 by inhibiting METTL3. Treatment with PBP10 (an inhibitor of the LXA4 receptor) abolished the inhibition of METTL3 by LXA4 and consequently reduced the tumorigenicity of prostate cancer cells. Altogether, this work demonstrated that prostate cancer cells facilitate polarization of M2 like macrophages by releasing LXA4 via inhibiting METTL3. These findings provide new insight into the mechanism of microenvironmental regulation of macrophage polarization during prostate cancer progression.


Assuntos
Lipoxinas , Neoplasias da Próstata , Linhagem Celular Tumoral , Humanos , Ativação de Macrófagos , Macrófagos , Masculino , Metiltransferases
16.
Front Microbiol ; 13: 1001750, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36687617

RESUMO

Traditional plastics, such as polyethylene (PE), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyurethane (PUR), and other plastic polymers, are difficult to degrade and are gradually accumulated in the environment to cause a serious environmental problem, which is urgently needed to develop novel treatments or control technology. The biodegradation of plastics has gained great attention due to the advantages of green and safe characteristics. Microorganisms play a vital role in the biodegradation of plastics, including environmental microbes (in vitro) and gut microbes of insects (in vivo). Microbial degradation in environmental conditions in vitro is extremely slow for major plastics at degradation rates on the basis of a month or even a year time, but recent discoveries show that the fast biodegradation of specific plastics, such as PS, PE, and PUR, in some invertebrates, especially insects, could be enhanced at rates on basis of hours; the biodegradation in insects is likely to be gut microbial-dependent or synergetic bioreactions in animal digestive systems. This review comprehensively summarizes the latest 7-year (2016-2022) publications on plastic biodegradation by insects and microorganisms, elucidates the mechanism of plastic degradation in insects and environmental microbes, and highlights the cutting-edge perspectives for the potential applications of plastic biodegradation.

17.
Ann Transl Med ; 9(12): 993, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277793

RESUMO

BACKGROUND: Asthma is a heterogeneous disease with different phenotypes, endotypes and responses to treatment. Dust mite allergic asthma (DMAA) is the most common type in children. Compared with randomized control trials, a patient registry study (PRS) can reflect the real physical condition and clinical diagnosis more comprehensively. METHODS: Children who visited the asthma clinic of the Children's Hospital of Chongqing Medical University between August 2018 and August 2020, and met the inclusion criteria and also agreed to participate, were enrolled in the registry study. Clinical information, laboratory tests and peripheral blood samples were collected after informed consent was given by guardians. RESULTS: To date, 208 children have been enrolled in the patient registry database of DMAA. They are mainly male, with >50% having a history of allergic rhinitis, cesarean section, positive family history and passive smoking. Eosinophils and total immunoglobulin E levels were all significantly higher than normal. According to results for the childhood asthma control test (c-ACT) and ratio of forced expiratory volume in 1 s to predicted value after inhaled corticosteroid treatment, the uncontrolled group had higher hemoglobin (Hb) levels than the control group. The group exhibiting abnormal pulmonary function was older, and had longer disease duration, higher fractional exhaled nitric oxide and Hb than the group in which pulmonary function was restored. CONCLUSIONS: We have preliminarily established a registered study database of children with DMAA. By cluster analysis and using blood samples, we can further study the different pathophysiological mechanisms in order to provide more individualized and targeted treatments for all children.

18.
J Cancer Res Ther ; 17(2): 543-546, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34121705

RESUMO

OBJECTIVE: The objective of this study is to explore the radiosensitization effects of duramycin against the liver cancer hepatoma cells and relationship to reactive oxygen species (ROS) generation. MATERIALS AND METHODS: MCA-RH 7777 cells were treated with various combinations of duramycin concentrations and radiation doses. After the treatment, cell viabilities were determined by a cell proliferation assay; intracellular ROS levels were detected with the flow cytometric method. RESULTS: MCA-RH 7777 cell viability was found significantly reduced after combining duramycin and radiation exposure (comparing to that of either treatment alone). Increased intracellular ROS levels were observed in cells treated with combinations of duramycin and radiation. CONCLUSION: Duramycin increased the intracellular ROS generation and also increased the radiosensitivity of MCA-RH 7777 cells.


Assuntos
Bacteriocinas/farmacologia , Carcinoma Hepatocelular/terapia , Quimiorradioterapia/métodos , Neoplasias Hepáticas/terapia , Peptídeos/farmacologia , Radiossensibilizantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Bacteriocinas/uso terapêutico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Hepáticas/patologia , Peptídeos/uso terapêutico , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo
19.
J Vasc Interv Radiol ; 32(8): 1103-1112.e12, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33839262

RESUMO

PURPOSE: To investigate the feasibility, safety, and absorbed-dose distribution of prostatic artery radioembolization (RE) in a canine model. MATERIALS AND METHODS: Fourteen male castrated beagles received dihydroandrosterone/estradiol to induce prostatic hyperplasia for the duration of the study. Each dog underwent fluoroscopic prostatic artery catheterization. Yttrium-90 (90Y) microspheres (TheraSphere; Boston Scientific, Marlborough, Massachusetts) were delivered to 1 prostatic hemigland (dose escalation from 60 to 200 Gy), with the contralateral side serving as a control. Assessments for adverse events were performed throughout the follow-up (Common Terminology Criteria for Adverse Events v5.0). Positron emission tomography/magnetic resonance (MR) imaging provided a confirmation after the delivery of absorbed-dose distribution. MR imaging was performed before and 3, 20, and 40 days after RE. Tissue harvest of the prostate, rectum, bladder, urethra, penis, and neurovascular bundles was performed 60 days after RE. RESULTS: All the animals successfully underwent RE. Positron emission tomography/MR imaging demonstrated localization to and good coverage of only the treated hemigland. No adverse events occurred. The MR imaging showed a significant dose-dependent decrease in the treated hemigland size at 40 days (25%-60%, P < .001). No extraprostatic radiographic changes were observed. Necropsy demonstrated no gross rectal, urethral, penile, or bladder changes. Histology revealed RE-induced changes in the treated prostatic tissues of the highest dose group, with gland atrophy and focal necrosis. No extraprostatic RE-related histologic findings were observed. CONCLUSIONS: Prostate 90Y RE is safe and feasible in a canine model and leads to focal dose-dependent changes in the gland without inducing unwanted extraprostatic effects. These results suggest that an investigation of nonoperative prostate cancer is warranted.


Assuntos
Braquiterapia , Embolização Terapêutica , Neoplasias da Próstata , Animais , Cães , Humanos , Masculino , Próstata , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioisótopos de Ítrio
20.
BMC Neurol ; 21(1): 122, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731033

RESUMO

BACKGROUND: To investigate the relationship between the position of bilateral STN-DBS location of active contacts and the clinical efficacy of STN-DBS on motor symptoms in Parkinson's disease (PD) patients. METHODS: Retrospectively analyze the clinical data of 57 patients with PD who underwent bilateral STN-DBS from March 2018 to December 2018. Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) score, levodopa equivalent day dose (LEDD), Parkinson's Disease Quality of Life Scale (PDQ-39) before operation and within 6 months after operation, determine the location of activated contacts and volume of tissue activated (VTA) in the Montreal Neurological Institute (MNI) space, and analyze their correlation with the improvement rate of motor symptoms (UPDRS-III score improvement rate). RESULTS: After 6 months of follow up, the UPDRS-III scores of 57 patients (Med-off) were improved by 55.4 ± 18.9% (P<0.001) compared with that before operation. The improvement rate of PDQ-39 scores [(47.4 ± 23.2)%, (P < 0.001)] and the reduction rate of LEDD [(40.1 ± 24.3)%, (P < 0.01)] at 6 months postoperation were positively correlated with the improvement rate of motor symptoms (Med-off)(PDQ-39:r = 0.461, P<0.001; LEDD: r = 0.354, P = 0.007), the improvement rate of UPDRS-III (Med-off) and the Z-axis coordinate of the active contact in the MNI space were positively correlated (left side: r = 0.349,P = 0.008;right side: r = 0.369,P = 0.005). In the MNI space, there was no correlation between the UPDRS-III scores improvement rate (Med-off) at 6 months after operation and bilateral VTA in the STN motor subregion, STN associative subregion and STN limbic subregion of the active electrode contacts of 57 patients (all P > 0.05). At 6 months after surgery, the difference between the Z-axis coordinate in the different improvement rate subgroups(<25, 25 to 50%, and>50%) in the MNI space was statistically significant (left side: P = 0.030; right side: P = 0.024). In the MNI space, there was no statistically significant difference between the groups in the VTA of the electrode active contacts (all P > 0.05). CONCLUSION: STN-DBS can improve the motor symptoms of PD patients and improve the quality of life. The closer the stimulation is to the STN dorsolateral sensorimotor area, the higher the DBS is to improve the motor symptoms of PD patients.


Assuntos
Estimulação Encefálica Profunda/métodos , Doença de Parkinson/terapia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Eletrodos , Feminino , Humanos , Levodopa/administração & dosagem , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Estudos Retrospectivos , Núcleo Subtalâmico , Resultado do Tratamento
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