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1.
Immunity ; 48(1): 161-173.e5, 2018 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-29305140

RESUMO

Acute hepatitis A (AHA) involves severe CD8+ T cell-mediated liver injury. Here we showed during AHA, CD8+ T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8+ T cells. TCR-independent activation of non-HAV-specific CD8+ T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8+ T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement. We demonstrated that the severity of liver injury in AHA patients correlated with the activation of HAV-unrelated virus-specific CD8+ T cells and the innate-like cytolytic activity of CD8+ T cells, but not the activation of HAV-specific T cells. Thus, host injury in AHA is associated with innate-like cytotoxicity of bystander-activated CD8+ T cells, a result with implications for acute viral diseases.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Citotoxicidade Imunológica/imunologia , Hepatite A/imunologia , Hepatopatias/imunologia , Ativação Linfocitária/imunologia , Adolescente , Adulto , Testes Imunológicos de Citotoxicidade , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunofluorescência , Hepatite A/complicações , Humanos , Immunoblotting , Interleucina-15/metabolismo , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
2.
Proc Natl Acad Sci U S A ; 121(8): e2316871121, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38346184

RESUMO

Postmenopausal osteoporosis arises from imbalanced osteoclast and osteoblast activity, and mounting evidence suggests a role for the osteoimmune system in bone homeostasis. Bisphosphonate (BP) is an antiresorptive agent, but its treatment failure rate can be as high as 40%. Here, we performed single-cell RNA sequencing on peripheral immune cells from carefully selected postmenopausal women: non-osteoporotic, osteoporosis improved after BP treatment, and BP-failed cases. We found an increase in myeloid cells in patients with osteoporosis (specifically, T cell receptor+ macrophages). Furthermore, lymphoid lineage cells varied significantly, notably elevated natural killer cells (NKs) in the BP-failed group. Moreover, we provide fruitful lists of biomarkers within the immune cells that exhibit condition-dependent differences. The existence of osteoporotic- and BP-failure-specific cellular information flows was revealed by cell-cell interaction analysis. These findings deepen our insight of the osteoporosis pathology enhancing comprehension of the role of immune heterogeneity in postmenopausal osteoporosis and BP treatment failure.


Assuntos
Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Humanos , Feminino , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/genética , Densidade Óssea , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/genética , Perfilação da Expressão Gênica
3.
Anal Chem ; 96(25): 10246-10255, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38858132

RESUMO

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.


Assuntos
Ensaios de Triagem em Larga Escala , Neoplasias Pulmonares , Organoides , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Organoides/metabolismo , Organoides/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia Celular , Técnicas de Cultura de Células em Três Dimensões , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
4.
Anal Biochem ; 692: 115571, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38796119

RESUMO

Markers of myocardial injury, such as myoglobin (Mb), are substances swiftly released into the peripheral bloodstream upon myocardial cell injury or altered cardiac activity. During the onset of acute myocardial infarction, patients experience a significant surge in serum Mb levels. Given this, precise detection of Mb is essential, necessitating the development of innovative assays to optimize detection capabilities. This study introduces the synthesis of a three-dimensional hierarchical nanocomposite, Cubic-ZIF67@Au-rGOF-NH2, utilizing aminated reduced graphene oxide and zeolite imidazolium ester framework-67 (ZIF67) as foundational structures. Notably, this novel material, applied in a label-free electrochemical immunosensor, presents a groundbreaking approach for detecting myocardial injury markers. Experimental outcomes revealed ZIF67 and AuNPs exhibit enhanced affinity and growth on the 3D-rGOF-NH2 matrix, thus amplifying electrical conductivity while preserving the inherent electrochemical attributes of ZIF67. As a result, the Cubic-ZIF67@Au-rGOF-NH2 label-free electrochemical immunosensor exhibited a broad detection range and high sensitivity for Mb. The derived standard curve was ΔIp = 16.67552lgC+275.245 (R = 0.993) with a detection threshold of 3.47 fg/ml. Moreover, recoveries of standards spiked into samples ranged between 96.3% and 108.7%. Importantly, the devised immunosensor retained notable selectivity against non-target proteins, proving its potential clinical utility based on exemplary sample analysis performance.


Assuntos
Técnicas Eletroquímicas , Ouro , Grafite , Estruturas Metalorgânicas , Mioglobina , Mioglobina/análise , Técnicas Eletroquímicas/métodos , Grafite/química , Estruturas Metalorgânicas/química , Ouro/química , Humanos , Técnicas Biossensoriais/métodos , Nanocompostos/química , Zeolitas/química , Imidazóis/química , Limite de Detecção , Nanopartículas Metálicas/química
5.
Scand J Gastroenterol ; 59(6): 749-754, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38380637

RESUMO

BACKGROUND AND AIMS: Diagnostic colonoscopy plays a central role in colorectal cancer screening programs. We analyzed the risk factors for perforation during diagnostic colonoscopy and discussed the treatment outcomes. METHODS: We performed a retrospective analysis of risk factors and treatment outcomes of perforation during 74,426 diagnostic colonoscopies between 2013 and 2018 in a tertiary hospital. RESULTS: A total of 19 perforations were identified after 74,426 diagnostic colonoscopies or sigmoidoscopies, resulting in a standardized incidence rate of 0.025% or 2.5 per 10,000 colonoscopies. The majority (15 out of 19, 79%) were found at the sigmoid colon and recto-sigmoid junction. Perforation occurred mostly in less than 1000 cases of colonoscopy (16 out of 19, 84%). In particular, the incidence of perforation was higher in more than 200 cases undergoing slightly advanced colonoscopy rather than beginners who had just learned colonoscopy. Old age (≥ 70 years), inpatient setting, low body mass index (BMI), and sedation status were significantly associated with increased risk of perforation. Nine (47%) of the patients underwent operative treatment and ten (53%) were managed non-operatively. Patients who underwent surgery were often diagnosed with delayed or concomitant abdominal pain. Perforations of rectum tended to be successfully treated with endoscopic clipping. CONCLUSIONS: Additional precautions are required to prevent perforation in elderly patients, hospital settings, low BMI, sedated patients, or by a doctor with slight familiarity with endoscopies (but still insufficient experience). Endoscopic treatment should be actively considered if diagnosis is prompt, abdominal pain absent, and especially the rectal perforation is present.


Assuntos
Colonoscopia , Doença Iatrogênica , Perfuração Intestinal , Humanos , Colonoscopia/efeitos adversos , Perfuração Intestinal/etiologia , Feminino , Masculino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Idoso de 80 Anos ou mais , Incidência , Adulto , Reto/lesões , Colo/lesões
6.
Dig Dis ; : 1-10, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38648736

RESUMO

INTRODUCTION: Endoscopic submucosal dissection (ESD) has been popular worldwide to treat laterally spreading tumors and large polyps. Post-ESD coagulation syndrome (PECS) is more common than the two major ESD-related complications, perforation, and bleeding. The aim of this study was to assess the prevalence of PECS, identify the risk factors for PECS, and create a risk prediction model for PECS. METHODS: Retrospective cross-sectional study analyzed a total of 986 patients who underwent colorectal ESD. Logistic regression models were used to assess risk factors with PECS. Each risk factor was scored, and the 3-step risk stratification index of prediction model was assessed. RESULTS: The prevalence of PECS was 21.4% (95% confidence interval [CI] = 18.9-24.1%). The risk factors of PECS in the multivariate logistic regression were tumor size (+1 cm: odds ratio [OR], 1.29; 95% CI, 1.16-7.09), cecal lesion (OR, 1.96; 95% CI, 1.09-1.53), procedure time (+30 min: OR, 1.19; 95% CI, 1.02-1.39), and ESD with snaring (OR, 0.64; 95% CI, 0.43-0.95). Applying a simplified weighted scoring system based on adjusted OR increments of 1, the risk of PECS was 12.3% (95% CI, 0.3-16.0%) for the low-risk group (score ≤4) and was 36.0% (95% CI = 29.4-43.2%) for the high-risk group (score ≥8). Overall discrimination (C-statistic = 0.629; 95% CI = 0.585-0.672) and calibration (p = 0.993) of the model were moderate to good. CONCLUSION: PECS occurs frequently, and the prediction model can be helpful for effective treatment and prevention of PECS.

7.
Br J Anaesth ; 132(2): 267-276, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042725

RESUMO

BACKGROUND: Intraoperative opioid use has a positive relationship with postoperative nausea and vomiting (PONV), and opioid-free anaesthesia (OFA) might reduce PONV. We investigated whether OFA compared with opioid-based anaesthesia would reduce PONV during the first 2 postoperative days among patients undergoing thoracoscopic lung resection. METHODS: In this randomised controlled trial, 120 adult patients were randomly assigned (1:1, stratified by sex) to receive either OFA with esketamine, dexmedetomidine, and sevoflurane, or opioid-based anaesthesia with sufentanil and sevoflurane. A surgical pleth index (SPI) of 20-50 was applied for intraoperative analgesia provision. All subjects received PONV prophylaxis (dexamethasone and ondansetron) and multimodal analgesia (flurbiprofen axetil, ropivacaine wound infiltration, and patient-controlled sufentanil). The primary outcome was the occurrence of PONV during the first 48 h after surgery. RESULTS: The median age was 53 yr and 66.7% were female. Compared with opioid-based anaesthesia, OFA significantly reduced the incidence of PONV (15% vs 31.7%; odds ratio [OR]=0.38, 95% confidence interval [CI], 0.16-0.91; number needed to treat, 6; P=0.031). Secondary and safety outcomes were comparable between groups, except that OFA led to a lower rate of vomiting (OR=0.23, 95% CI, 0.08-0.77) and a longer length of PACU stay (median difference=15.5 min, 95% CI, 10-20 min). The effects of OFA on PONV did not differ in the prespecified subgroups of sex, smoking status, and PONV risk scores. CONCLUSIONS: In the context of PONV prophylaxis and multimodal analgesia, SPI-guided opioid-free anaesthesia halved the incidence of PONV after thoracoscopic lung resection, although it was associated with a longer stay in the PACU. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200059710).


Assuntos
Anestesia , Náusea e Vômito Pós-Operatórios , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Náusea e Vômito Pós-Operatórios/prevenção & controle , Analgésicos Opioides/uso terapêutico , Sufentanil/uso terapêutico , Sevoflurano/uso terapêutico , Pulmão , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico
8.
Eur Spine J ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888800

RESUMO

PURPOSE: Vertebral Body Tethering (VBT) has been shown to have a less predictable outcome compared to spinal fusion in patients with adolescent idiopathic scoliosis (AIS). Tether breakage is a common mechanical event that sometimes leads to loss of correction. No data has been published that evaluates the outcome of re-tethering in patients who underwent revision surgery for failed VBT, which was the purpose of this study. METHODS: This is an analysis of a prospectively collected single center database of 290 patients who have had VBT. Patients for this study were included if they have had re-tethering after failed VBT and a minimum follow up of 24 months after index surgery as well as a minimum follow up of 12 months after revision surgery. Revision surgeries included tether exchange, tether reinforcement and/or mono- and bisegmental lateral fusion. Main outcome of interest was curve magnitude at latest follow up. RESULTS: 11 patients were identified who received VBT for 16 curves of which 13 curves have had failed index surgery. Mean follow up from index surgery was 40 months, time between index and revision surgery was 22 months and latest follow up after revision surgery 19 months. Re-tethering resulted in an additional correction of 42% for thoracic and 63% for thoracolumbar curves. These results remained clinically stable with only minor loss of correction at final follow up. No patient underwent or was indicated for spinal fusion. CONCLUSION: Re-tethering is feasible and able to achieve additional correction and a sustainable result.

9.
Eur Spine J ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753189

RESUMO

PURPOSE: Spinal fusion is the standard treatment for severe forms of adolescent idiopathic scoliosis (AIS). However, with the lowest instrumented vertebra that is usually located at L3 or L4, patients are prone to develop adjacent segment degeneration in the long term. Vertebral body tethering (VBT) as motion preserving technique has become an alternative for select patients with AIS. Several studies have presented the outcome after thoracic VBT but no study has analyzed the outcome after VBT for Lenke type 6 curves. METHODS: This is a retrospective single center data analysis of patients who have had bilateral VBT for Lenke type 6 curves and a minimum follow up of 24 months. Radiographic analysis was performed on several time points. Suspected tether breakages were additionally analyzed with respect to location and time at occurrence. RESULTS: 25 patients were included. Immediate thoracic curve correction was 55.4% and 71.7% for TL/L curves. Loss of correction was higher for TL/L curves and resulted in a correction rate of 48.3% for thoracic curves and 48.9% for TL/L curves at 24 months post-operatively. 22 patients were suspected to have at least one segment with a tether breakage. Three patients required a re-VBT but no patient received posterior spinal fusion. CONCLUSION: Bilateral VBT for Lenke type 6 curves is feasible and shows a significant curve correction for thoracic and TL/L curves at a minimum of 24 months post-operatively. Tether breakage rate and loss of correction remain an unfavorable observation that needs to be improved in the future.

10.
Eur Spine J ; 33(6): 2530-2535, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38615086

RESUMO

INTRODUCTION: Vertebral body tethering (VBT) has become an alternative option for select patients with idiopathic scoliosis. However, studies have shown a high number of tether breakages, specifically after thoracolumbar (TL) VBT, that can have a negative impact on the outcome, when the breakage occurs within the first year after surgery. In order to overcome this problem, we have started to apply an apical fusion (AF) in combination with TL VBT for select patients. This study aims to analyze the outcome after AF plus VBT. METHODS: This is a retrospective single surgeon's data analysis. All patients were included who have had TL VBT after January 2022 and a follow-up of 12 months. Patients were grouped based on whether they only had VBT or VBT + AF. RESULTS: Twenty-five patients were analyzed (15 VBT, 10 VBT + AF). Both groups showed a significant curve correction for thoracic and TL curves. Minor loss of correction was observed in both groups. A significant difference was seen regarding early tether breakages, which were found in 60% of VBT patients and 10% of VBT + AF patients. CONCLUSION: The preliminary data shows a significant reduction of early tether breakages when TL VBT is applied in combination with AF.


Assuntos
Vértebras Lombares , Escoliose , Fusão Vertebral , Vértebras Torácicas , Humanos , Escoliose/cirurgia , Escoliose/diagnóstico por imagem , Fusão Vertebral/métodos , Feminino , Vértebras Torácicas/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Adolescente , Masculino , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento , Corpo Vertebral/cirurgia , Corpo Vertebral/diagnóstico por imagem , Criança
11.
Eur Spine J ; 33(1): 324-331, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37558910

RESUMO

PURPOSE: Adjacent segment disease (ASD) is a common complication in fusion surgery. In the event of solid segmental fusion, previous implants can be removed or preserved during fusion extension for ASD. To compare the surgical outcomes of patients with and without implants and analyzes the risk factors for postoperative mechanical complications. METHODS: Patients who underwent fusion extension for lumbar ASD from 2011 to 2019 with a minimum 2 year follow-up were retrospectively reviewed. Spinopelvic parameters were measured preoperatively and postoperatively. Clinical outcomes and surgical complications were compared between groups with implants preserved and removed. Risk factors for mechanical complications, including clinical, surgical, and radiographic factors were analyzed. RESULTS: Sixty-nine patients (mean age, 69.9 ± 6.9 years) were included. The mean numbers of initial and extended fused segments were 2.8 ± 0.7 and 2.7 ± 0.7, respectively. Previous implants were removed in 43 patients (R group) and preserved in 26 patients (P group). Both groups showed an improvement in clinical outcomes without between-group differences. The operation time was significantly longer in R group (260 vs 207 min, p < 0.001). Mechanical complications occurred in 13 patients (12 in R group and 1 in P group) and reoperation was needed in 3 patients (R group). Implant removal, index fusion surgery including L5-S1, and postoperative sagittal malalignment were risk factors for mechanical complications. CONCLUSION: Implant removal was a risk factor for mechanical complications. Index fusion surgery including L5-S1 and postoperative sagittal malalignment were also risk factors for mechanical complications.


Assuntos
Complicações Pós-Operatórias , Fusão Vertebral , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Próteses e Implantes , Reoperação , Fatores de Risco , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/efeitos adversos
12.
J Med Internet Res ; 26: e52001, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38924787

RESUMO

BACKGROUND: Due to recent advances in artificial intelligence (AI), language model applications can generate logical text output that is difficult to distinguish from human writing. ChatGPT (OpenAI) and Bard (subsequently rebranded as "Gemini"; Google AI) were developed using distinct approaches, but little has been studied about the difference in their capability to generate the abstract. The use of AI to write scientific abstracts in the field of spine surgery is the center of much debate and controversy. OBJECTIVE: The objective of this study is to assess the reproducibility of the structured abstracts generated by ChatGPT and Bard compared to human-written abstracts in the field of spine surgery. METHODS: In total, 60 abstracts dealing with spine sections were randomly selected from 7 reputable journals and used as ChatGPT and Bard input statements to generate abstracts based on supplied paper titles. A total of 174 abstracts, divided into human-written abstracts, ChatGPT-generated abstracts, and Bard-generated abstracts, were evaluated for compliance with the structured format of journal guidelines and consistency of content. The likelihood of plagiarism and AI output was assessed using the iThenticate and ZeroGPT programs, respectively. A total of 8 reviewers in the spinal field evaluated 30 randomly extracted abstracts to determine whether they were produced by AI or human authors. RESULTS: The proportion of abstracts that met journal formatting guidelines was greater among ChatGPT abstracts (34/60, 56.6%) compared with those generated by Bard (6/54, 11.1%; P<.001). However, a higher proportion of Bard abstracts (49/54, 90.7%) had word counts that met journal guidelines compared with ChatGPT abstracts (30/60, 50%; P<.001). The similarity index was significantly lower among ChatGPT-generated abstracts (20.7%) compared with Bard-generated abstracts (32.1%; P<.001). The AI-detection program predicted that 21.7% (13/60) of the human group, 63.3% (38/60) of the ChatGPT group, and 87% (47/54) of the Bard group were possibly generated by AI, with an area under the curve value of 0.863 (P<.001). The mean detection rate by human reviewers was 53.8% (SD 11.2%), achieving a sensitivity of 56.3% and a specificity of 48.4%. A total of 56.3% (63/112) of the actual human-written abstracts and 55.9% (62/128) of AI-generated abstracts were recognized as human-written and AI-generated by human reviewers, respectively. CONCLUSIONS: Both ChatGPT and Bard can be used to help write abstracts, but most AI-generated abstracts are currently considered unethical due to high plagiarism and AI-detection rates. ChatGPT-generated abstracts appear to be superior to Bard-generated abstracts in meeting journal formatting guidelines. Because humans are unable to accurately distinguish abstracts written by humans from those produced by AI programs, it is crucial to exercise special caution and examine the ethical boundaries of using AI programs, including ChatGPT and Bard.


Assuntos
Indexação e Redação de Resumos , Coluna Vertebral , Humanos , Coluna Vertebral/cirurgia , Indexação e Redação de Resumos/normas , Indexação e Redação de Resumos/métodos , Reprodutibilidade dos Testes , Inteligência Artificial , Redação/normas
13.
Sensors (Basel) ; 24(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38894390

RESUMO

Chemical warfare agents pose a serious threat due to their extreme toxicity, necessitating swift the identification of chemical gases and individual responses to the identified threats. Fourier transform infrared (FTIR) spectroscopy offers a method for remote material analysis, particularly in detecting colorless and odorless chemical agents. In this paper, we propose a deep neural network utilizing a semi-supervised autoencoder (SSAE) for the classification of chemical gases based on FTIR spectra. In contrast to traditional methods, the SSAE concurrently trains an autoencoder and a classifier attached to a latent vector of the autoencoder, enhancing feature extraction for classification. The SSAE was evaluated on laboratory-collected FTIR spectra, demonstrating a superior classification performance compared to existing methods. The efficacy of the SSAE lies in its ability to generate denser cluster distributions in latent vectors, thereby enhancing gas classification. This study established a consistent experimental environment for hyperparameter optimization, offering valuable insights into the influence of latent vectors on classification performance.

14.
Biochem Biophys Res Commun ; 681: 225-231, 2023 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-37783121

RESUMO

The commitment of mesenchymal stem cells (MSCs) to preadipocytes and the termination of differentiation to adipocytes are critical for maintaining systemic energy homeostasis. However, our knowledge of the molecular mechanisms governing the commitment of MSCs to preadipocytes and the subsequent termination of their differentiation into adipocytes remain limited. Additionally, the role of Sox6 sex-determining region Y (SRY)-box6 (Sox6), a transcription factor that regulates gene transcription, is reportedly involved in various cellular processes, including adipogenesis; however, its function in regulating preadipocyte development and the factors involved in the termination of adipogenic differentiation remain unexplored. Therefore, we investigated the role of Sox6 in regulating the differentiation of adipocytes by monitoring the effects of its overexpression in C3H10T1/2 cells (in vitro) and C57BL/6J mouse (in vivo) models of adipogenesis. We observed lower Sox6 expression in the adipose tissue of obese mice than that in control mice. Sox6 overexpression inhibited the differentiation of MSC by directly binding to the lysyl oxidase (Lox) and preadipocyte factor 1 (Pref1) promoters, which was potentiated by histone deacetylase-1(HDAC1). Our findings suggest that Sox6 is a key regulator of MSC commitment to adipocytes; therefore, targeting the Sox6-mediated regulation of this process could offer potential therapeutic avenues for addressing obesity and related metabolic disorders.


Assuntos
Adipogenia , Células-Tronco Mesenquimais , Animais , Camundongos , Adipogenia/genética , Diferenciação Celular/genética , Camundongos Endogâmicos C57BL , Proteína-Lisina 6-Oxidase/genética , Proteína-Lisina 6-Oxidase/metabolismo , Fatores de Transcrição SOXD/genética , Fatores de Transcrição SOXD/metabolismo
15.
Anal Biochem ; 676: 115233, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37433362

RESUMO

Exosomes derived from lung cancer typically contain the genetic information of the donor cells. Therefore, exosomes contribute to early diagnosis, treatment effectiveness evaluation, and prognosis assessment of cancer. Based on the biotin-streptavidin system and MXenes nanomaterial, a dual-effect amplification method had been developed to construct an ultrasensitive colorimetric aptasensor for detecting exosomes. MXenes can enhance the loading of aptamer and biotin as the high specific surface area. Biotin-streptavidin system can increase the amount of horseradish peroxidase-linked (HRP-linked) streptavidin, considerably boosting the color signal of the aptasensor. The proposed colorimetric aptasensor exhibited excellent sensitivity, with a detection limit of 42 particles µL-1 and a linear range of 102 to 107 particles µL-1. The constructed aptasensor showed satisfactory reproducibility, stability, and selectivity, confirming the promising application of exosomes in clinical cancer detection.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exossomos , Estreptavidina , Biotina , Reprodutibilidade dos Testes , Técnicas Biossensoriais/métodos , Limite de Detecção
16.
Protein Expr Purif ; 203: 106214, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36526214

RESUMO

Hepatitis E is an emerging zoonotic disease, posing a severe threat to public health in the world. Since there are no specific treatments available for HEV infection, it is crucial to develop vaccine to prevent this infection. In this study, the truncated ORF2 encoded protein of 439aa∼617aa (HEV3-179) from HEV CCJD-517 isolates was expressed as VLPs in E. coli with diameters of approximate 20 nm. HEV3-179 protein was immunized with mice, and the results showed that a higher titre of antibody was induced in NIH mice in comparison with that of KM mice (P < 0.01) and BALB/c mice (P < 0.01). The induced antibody titer is much higher in subcutaneous immunization mice than that in the mice inoculated via abdominal immunization (P < 0.05) and muscles immunization (P < 0.01). Mice immunized with 12 µg and 6 µg candidate vaccine induced higher level of antibody titer than that of 3 µg dosage group (P < 0.01, P < 0.05). Antibody change curve showed that HEV IgG antibody titer increased from 14 days post immunization (dpi) to 1:262144 and reached the peak level on 42 dpi before gradually retreated with the same level antibody titer with 1:131072 until 84 dpi. Mice inoculated with HEV3-179 produced higher titer of cytokines than the mock group, and the concentration of IL-1ß (P < 0.01) and IFN-γ (P < 0.01) further increased after stimulated by candidate vaccine. The result indicated that HEV3-179 possesses good immunogenicity, which could be used as a potential candidate for future HEV vaccine development.


Assuntos
Vírus da Hepatite E , Hepatite E , Vacinas de Partículas Semelhantes a Vírus , Animais , Camundongos , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Escherichia coli , Hepatite E/prevenção & controle , Vírus da Hepatite E/genética , Vírus da Hepatite E/imunologia , Imunização , Proteínas Recombinantes/genética , Partículas Artificiais Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia
17.
BMC Gastroenterol ; 23(1): 331, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37759282

RESUMO

There are limited studies on the endoscopic assessment of disease activity using balloon-assisted enteroscopy (BAE) and its predictive role for long-term outcomes of patients with small bowel Crohn's disease (CD). We sought to investigate the value of BAE as a predictor of long-term outcomes in patients with small-bowel CD. A total of 111 patients with small-bowel CD whose endoscopic disease activity was assessed using BAE based on the small-bowel simple endoscopic score for Crohn's disease (small-bowel SES-CD) at Samsung Medical Center were retrospectively selected from January 2014 to August 2020. The outcome was an evaluation of the risk of surgery according to a small-bowel SES-CD of 0-6 vs. ≥ 7 and endoscopic findings (presence of any ulcer and degree of stricture) using the Cox proportional hazards model. The risk of surgery was significantly increased in patients with a small-bowel SES-CD of ≥ 7 compared to a small-bowel SES-CD of 0-6 [hazard ratio (HR) 6.31; 95% confidence interval (CI) 1.48-26.91; p = 0.013]. In addition, the risk of surgery was significantly increased in patients with stenosis with "cannot be passed" compared to the cases without stenosis (HR 12.34; 95% CI 1.66-91.92; p = 0.014), whereas there was no significance in any ulcer. The present study demonstrated the role of BAE in the endoscopic assessment of disease activity and its predictive value for the risk of surgery in small-bowel CD patients. Further optimization of BAE utilization for the assessment of disease activity is warranted in clinical practice.


Assuntos
Doença de Crohn , Enteropatias , Humanos , Doença de Crohn/complicações , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/cirurgia , Constrição Patológica/etiologia , Estudos Retrospectivos , Úlcera
18.
BMC Cardiovasc Disord ; 23(1): 234, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37142962

RESUMO

BACKGROUND: The importance of inflammation in thrombosis is increasingly appreciated. Neutrophil-lymphocyte ratio (NLR) and monocyte to high-density lipoprotein ratio (MHR) are important indicators of systemic inflammation. This study aimed to investigate the associations between NLR and MHR with left atrial appendage thrombus (LAAT) and spontaneous echo contrast (SEC) in patients with non-valvular atrial fibrillation. METHODS: This retrospective, cross-sectional study enrolled 569 consecutive patients with non-valvular atrial fibrillation. Multivariable logistic regression analysis was used to investigate independent risk factors of LAAT/SEC. Receiver operating characteristic (ROC) curves were used to evaluate the specificity and sensitivity of NLR and MHR in predicting LAAT/SEC. Subgroup and Pearson correlation analyses were used to assess the correlations between NLR and MHR with the CHA2DS2-VASc score. RESULTS: Multivariate logistic regression analysis showed that NLR (OR: 1.49; 95%CI: 1.173-1.892) and MHR (OR: 2.951; 95%CI: 1.045-8.336) were independent risk factors for LAAT/SEC. The area under the ROC curve of NLR (0.639) and MHR (0.626) was similar to that of the CHADS2 score (0.660) and CHA2DS2-VASc score (0.637). Subgroup and Pearson correlation analyses showed significant but very weak associations between NLR (r = 0.139, P < 0.05) and MHR (r = 0.095, P < 0.05) with the CHA2DS2-VASc score. CONCLUSION: Generally, NLR and MHR are independent risk factors for predicting LAAT/SEC in patients with non-valvular atrial fibrillation.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Cardiopatias , Trombose , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Apêndice Atrial/diagnóstico por imagem , Neutrófilos , Lipoproteínas HDL , Monócitos , Estudos Retrospectivos , Estudos Transversais , Ecocardiografia Transesofagiana/efeitos adversos , Trombose/diagnóstico por imagem , Trombose/etiologia , Fatores de Risco , Cardiopatias/complicações , Linfócitos , Inflamação/complicações
19.
Pacing Clin Electrophysiol ; 46(9): 1035-1048, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37573146

RESUMO

Transcatheter radiofrequency ablation has been widely introduced for the treatment of tachyarrhythmias. The demand for catheter ablation continues to grow rapidly as the level of recommendation for catheter ablation. Traditional catheter ablation is performed under the guidance of X-rays. X-rays can help display the heart contour and catheter position, but the radiobiological effects caused by ionizing radiation and the occupational injuries worn caused by medical staff wearing heavy protective equipment cannot be ignored. Three-dimensional mapping system and intracardiac echocardiography can provide detailed anatomical and electrical information during cardiac electrophysiological study and ablation procedure, and can also greatly reduce or avoid the use of X-rays. In recent years, fluoroless catheter ablation technique has been well demonstrated for most arrhythmic diseases. Several centers have reported performing procedures in a purposefully designed fluoroless electrophysiology catheterization laboratory (EP Lab) without fixed digital subtraction angiography equipment. In view of the lack of relevant standardized configurations and operating procedures, this expert task force has written this consensus statement in combination with relevant research and experience from China and abroad, with the aim of providing guidance for hospitals (institutions) and physicians intending to build a fluoroless cardiac EP Lab, implement relevant technologies, promote the standardized construction of the fluoroless cardiac EP Lab.


Assuntos
Ablação por Cateter , Técnicas Eletrofisiológicas Cardíacas , Cirurgia Assistida por Computador , Humanos , Eletrofisiologia Cardíaca , Ablação por Cateter/métodos , Técnicas Eletrofisiológicas Cardíacas/métodos , Cirurgia Assistida por Computador/métodos , Resultado do Tratamento
20.
Pharmacoepidemiol Drug Saf ; 32(12): 1341-1349, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37366649

RESUMO

PURPOSE: Quetiapine is a drug used to treat schizophrenia, bipolar disorder, and major depressive disorder. However, it can cause mild or severe hepatic adverse events and rarely fatal liver damage. This study was aimed at investigating hepatic toxicity caused by quetiapine use by analyzing the information captured from hospital electronic health records by using the Observational Medical Outcomes Partnership common data model (CDM). METHODS: This was a retrospective observational study involving a nested case-control method. A CDM based on an electronic health record database from five hospitals between January 2009 and May 2020 was used. We analyzed the status of quetiapine use, adverse events, and hepatic impairment. RESULTS: The numbers of patients with non-serious and severe hepatic adverse reactions were 2566 (5.05%) and 835 (1.64%) out of 50 766 patients, respectively. After adjusting for covariates, the odds ratio of hepatic adverse events was 2.35 (95% CI: 2.03-2.72), and the odds ratio of severe hepatic adverse events was 1.76 (95% CI: 1.16-2.66). CONCLUSION: Our findings suggest that quetiapine should be cautiously used, and hepatic function should be monitored in patients using quetiapine because it can cause mild or severe hepatic adverse events, complications, and in rare cases, fatal liver damage.


Assuntos
Antipsicóticos , Transtorno Bipolar , Transtorno Depressivo Maior , Humanos , Fumarato de Quetiapina/efeitos adversos , Antipsicóticos/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Fígado
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