Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 362
Filtrar
1.
Nucleic Acids Res ; 51(9): 4284-4301, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-36864760

RESUMO

The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica , Cromatina , Músculo Liso Vascular , Neointima , Fenótipo , Animais , Humanos , Camundongos , Fatores de Transcrição de Zíper de Leucina Básica/deficiência , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Cromatina/genética , Cromatina/metabolismo , Homeostase , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Neointima/genética , Neointima/metabolismo , Neointima/patologia , Neointima/prevenção & controle , Placa Aterosclerótica
2.
J Cell Physiol ; 239(1): 97-111, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37921259

RESUMO

Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment, and the M2-type TAMs can promote tumor growth, invasion and angiogenesis, and suppress antitumor immune responses. It has been reported that spectrin beta, non-erythrocytic 1 (SPTBN1) may inhibit the infiltration of macrophages in Sptbn1+/-  mouse liver, but whether tumor SPTBN1 affects TAMs polarization remains unclear. This study investigated the effect and mechanism of tumor cell SPTBN1 on polarization and migration of TAMs in hepatoma and breast cancer. By analyzing tumor immune databases, we found a negative correlation between SPTBN1 and abundance of macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. By reverse transcription-quantitative real-time PCR assays and cell migration assays, the migration and M2 polarization of macrophages were enhanced by the culture medium from hepatocellular carcinoma cell line PLC/PRF/5, SNU449, and breast cancer cell line MDA-MB-231 with SPTBN1 suppression, which could be reversed by CXCL1 neutralizing antibody MAB275. Meanwhile, the ability of migration and colony formation of PLC/PRF/5, SNU449, and MDA-MB-231 cells were promoted when coculture with M2 macrophages. We also found that SPTBN1 regulated CXCL1 through p65 by cytoplasmic-nuclear protein isolation experiments and ChIP-qPCR. Our data suggest that tumor cell SPTBN1 inhibits migration and M2-type polarization of TAMs by reducing the expression and secretion of CXCL1 via inhibiting p65 nuclear localization.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Espectrina , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Neoplasias Hepáticas/metabolismo , Macrófagos/metabolismo , Microambiente Tumoral , Macrófagos Associados a Tumor/patologia , Humanos , Espectrina/metabolismo , Quimiocina CXCL1
3.
Cardiovasc Diabetol ; 23(1): 162, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724999

RESUMO

BACKGROUND: The triglyceride glucose-body mass index (TyG-BMI) is recognized as a reliable surrogate for evaluating insulin resistance and an effective predictor of cardiovascular disease. However, the link between TyG-BMI index and adverse outcomes in heart failure (HF) patients remains unclear. This study examines the correlation of the TyG-BMI index with long-term adverse outcomes in HF patients with coronary heart disease (CHD). METHODS: This single-center, prospective cohort study included 823 HF patients with CHD. The TyG-BMI index was calculated as follows: ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. To explore the association between the TyG-BMI index and the occurrences of all-cause mortality and HF rehospitalization, we utilized multivariate Cox regression models and restricted cubic splines with threshold analysis. RESULTS: Over a follow-up period of 9.4 years, 425 patients died, and 484 were rehospitalized due to HF. Threshold analysis revealed a significant reverse "J"-shaped relationship between the TyG-BMI index and all-cause mortality, indicating a decreased risk of all-cause mortality with higher TyG-BMI index values below 240.0 (adjusted model: HR 0.90, 95% CI 0.86-0.93; Log-likelihood ratio p = 0.003). A distinct "U"-shaped nonlinear relationship was observed with HF rehospitalization, with the inflection point at 228.56 (adjusted model: below: HR 0.95, 95% CI 0.91-0.98; above: HR 1.08, 95% CI 1.03-1.13; Log-likelihood ratio p < 0.001). CONCLUSIONS: This study reveals a nonlinear association between the TyG-BMI index and both all-cause mortality and HF rehospitalization in HF patients with CHD, positioning the TyG-BMI index as a significant prognostic marker in this population.


Assuntos
Biomarcadores , Glicemia , Índice de Massa Corporal , Doença das Coronárias , Insuficiência Cardíaca , Readmissão do Paciente , Triglicerídeos , Humanos , Masculino , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Triglicerídeos/sangue , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Glicemia/metabolismo , Fatores de Tempo , Biomarcadores/sangue , Medição de Risco , Fatores de Risco , Doença das Coronárias/mortalidade , Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Prognóstico , Causas de Morte , Resistência à Insulina , Valor Preditivo dos Testes
4.
Circ Res ; 130(7): 1038-1055, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35196865

RESUMO

BACKGROUND: The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation and migration and impaired angiogenesis in the ischemic hindlimbs of adult mice. However, the role and underlying mechanisms of BACH1 in atherosclerosis remain unclear. METHODS: Mouse models of atherosclerosis in endothelial cell (EC)-specific-Bach1 knockout mice were used to study the role of BACH1 in the regulation of atherogenesis and the underlying mechanisms. RESULTS: Genetic analyses revealed that coronary artery disease-associated risk variant rs2832227 was associated with BACH1 gene expression in carotid plaques from patients. BACH1 was upregulated in ECs of human and mouse atherosclerotic plaques. Endothelial Bach1 deficiency decreased turbulent blood flow- or western diet-induced atherosclerotic lesions, macrophage content in plaques, expression of endothelial adhesion molecules (ICAM1 [intercellular cell adhesion molecule-1] and VCAM1 [vascular cell adhesion molecule-1]), and reduced plasma TNF-α (tumor necrosis factor-α) and IL-1ß levels in atherosclerotic mice. BACH1 deletion or knockdown inhibited monocyte-endothelial adhesion and reduced oscillatory shear stress or TNF-α-mediated induction of endothelial adhesion molecules and/or proinflammatory cytokines in mouse ECs, human umbilical vein ECs, and human aortic ECs. Mechanistic studies showed that upon oscillatory shear stress or TNF-α stimulation, BACH1 and YAP (yes-associated protein) were induced and translocated into the nucleus in ECs. BACH1 upregulated YAP expression by binding to the YAP promoter. BACH1 formed a complex with YAP inducing the transcription of adhesion molecules. YAP overexpression in ECs counteracted the antiatherosclerotic effect mediated by Bach1-deletion in mice. Rosuvastatin inhibited BACH1 expression by upregulating microRNA let-7a in ECs, and decreased Bach1 expression in the vascular endothelium of hyperlipidemic mice. BACH1 was colocalized with YAP, and the expression of BACH1 was positively correlated with YAP and proinflammatory genes, as well as adhesion molecules in human atherosclerotic plaques. CONCLUSIONS: These data identify BACH1 as a mechanosensor of hemodynamic stress and reveal that the BACH1-YAP transcriptional network is essential to vascular inflammation and atherogenesis. BACH1 shows potential as a novel therapeutic target in atherosclerosis.


Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/patologia , Fatores de Transcrição/metabolismo
5.
J Periodontal Res ; 59(3): 565-575, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38240289

RESUMO

BACKGROUND AND OBJECTIVE: Clinical studies found high levels of hepatocyte growth factor (HGF) expression in patients with periodontitis. Studies suggest that HGF plays an important role in periodontitis, is involved in inflammation, and modulates alveolar bone integrity in periodontitis. This study aims to investigate the effects and mechanisms of HGF in the progression of experimental periodontitis. METHODS: We used silk thread ligation to induce periodontitis in HGF-overexpressing transgenic (HGF-Tg) and wild-type C57BL/6J mice. The effects of HGF overexpression on alveolar bone destruction were assessed by microcomputed tomography imaging at baseline and on days 7, 14, 21, and 28. We analyzed the cytokines (IL-6 and TNF-α) and lymphocytes in periodontitis tissues by enzyme-linked immunosorbent assay and flow cytometry. The effects of HGF on alveolar bone destruction were further tested by quantifying the systemic bone metabolism markers CTXI and PINP and by RNA sequencing for the signaling pathways involved in bone destruction. Western blotting and immunohistochemistry were performed to further elucidate the involved signaling pathways. RESULTS: We found that experimental periodontitis increased HGF production in periodontitis tissues; however, the effects of HGF overexpression were inconsistent with disease progression. In the early stage of periodontitis, periodontal inflammation and alveolar bone destruction were significantly lower in HGF-Tg mice than in wild-type mice. In the late stage, HGF-Tg mice showed higher inflammatory responses and progressively aggravated bone destruction with continued stimulation of inflammation. We identified the IL-17/RANKL/TRAF6 pathway as a signaling pathway involved in the HGF effects on the progression of periodontitis. CONCLUSION: HGF plays divergent effects in the progression of experimental periodontitis and accelerates osteoclastic activity and bone destruction in the late stage of inflammation.


Assuntos
Perda do Osso Alveolar , Fator de Crescimento de Hepatócito , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Periodontite , Microtomografia por Raio-X , Animais , Fator de Crescimento de Hepatócito/metabolismo , Periodontite/metabolismo , Periodontite/patologia , Camundongos , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/patologia , Modelos Animais de Doenças , Progressão da Doença , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Transdução de Sinais , Masculino , Ensaio de Imunoadsorção Enzimática
6.
Environ Res ; 263(Pt 1): 119978, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39278581

RESUMO

Since the addition of perfluorooctane sulfonate (PFOS) to the Stockholm Convention in 2009, it became imperative to reassess the distribution and ecological risk of per- and polyfluoroalkyl substances (PFAS) in coastal sediments over the past decade as sediment records the history of pollutants from human activities. To achieve this, sediments were collected in 2009 and 2021 from China's coastal regions. Despite the consistent geographical pattern where the highest concentrations of ∑PFAS were found in the Yellow Sea, temporal changes have emerged. During the studied period, ∑PFAS levels experienced an increase in the East China Sea while concurrently witnessing a decrease in the South China Sea. Of significance, emerging PFAS compounds displayed not only rising concentrations but also a broader array, pointing towards their intensified production and utilization within China. Alarmingly, PFOS levels in sediments taken from the East China Sea maintained a consistently high ecological risk status over the last ten years. Significant correlations were found between long-chain PFAS and organic carbon content. Comparisons between datasets from 2009 to 2021 uncovered a shifting ecological risk landscape, with heightened concerns for PFOA in the East China Sea, while PFOS-associated risks appeared to diminish in the South China Sea-potentially reflecting the transition to alternative PFAS chemicals. The research reinforces the importance of continuous monitoring and emphasizes the urgent necessity for deeper exploration into the environmental implications and hazards posed by emerging PFAS.

7.
Pediatr Radiol ; 54(4): 646-652, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38472490

RESUMO

Hand-wrist radiography is the most common and accurate method for evaluating children's bone age. To reduce the scattered radiation of radiosensitive organs in bone age assessment, we designed a small X-ray instrument with radioprotection function by adding metal enclosure for X-ray shielding. We used a phantom operator to compare the scattered radiation doses received by sensitive organs under three different protection scenarios (proposed instrument, radiation personal protective equipment, no protection). The proposed instrument showed greater reduction in the mean dose of a single exposure compared with radiation personal protective equipment especially on the left side which was proximal to the X-ray machine (≥80.0% in eye and thyroid, ≥99.9% in breast and gonad). The proposed instrument provides a new pathway towards more convenient and efficient radioprotection.


Assuntos
Proteção Radiológica , Criança , Humanos , Doses de Radiação , Raios X , Radiografia , Proteção Radiológica/métodos , Fluoroscopia , Imagens de Fantasmas
8.
BMC Oral Health ; 24(1): 536, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715009

RESUMO

BACKGROUND: Oral traumatic ulcerative lesions (OTUL) are commonly encountered in clinical practice, yet there is limited research on their clinical characteristics and traumatic etiological factors. This retrospective study aimed to analyze the age, gender, clinical characteristics, and traumatic etiological factors in a large cohort of patients with OTUL and provide valuable insights for dental clinicians to optimize patient care and prevention strategies. METHODS: A total of 1543 patients with OTUL were enrolled in this study. Age, gender, medical history, clinical characteristics and traumatic etiological factors were collected and analyzed. Logistic regression analysis was performed to determine the significance of age and gender as factors related to OTUL. RESULTS: The study revealed significant variations in clinical characteristics and traumatic etiological factors among different age groups and between genders. Logistic regression analysis demonstrated that both age and gender were significant factors related to OTUL. CONCLUSION: The clinical characteristics of OTUL and traumatic etiological factors appear to be significantly different according to age and gender. More targeted prevention strategies should be implemented for all age and gender groups.


Assuntos
Úlceras Orais , Humanos , Masculino , Feminino , Estudos Retrospectivos , Adulto , Fatores Sexuais , Pessoa de Meia-Idade , Fatores Etários , Úlceras Orais/etiologia , Adolescente , Adulto Jovem , Idoso , Criança , Pré-Escolar , Fatores de Risco , Idoso de 80 Anos ou mais
9.
BMC Oral Health ; 24(1): 935, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39135018

RESUMO

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disorder characterized by recurrent edema, facial palsies, and nerve dysfunctions often associated with the plicata tongue. Although the etiology of MRS is not well understood, there is growing evidence suggesting an autoimmune involvement. CASE PRESENTATION: This paper presents a case report of a 25-year-old male with MRS as the initial symptom, followed by temporomandibular joint osteoarthritis (TMJ-OA). A comprehensive diagnosis and multidisciplinary treatment approach including surgery, local injections, and oral medication were implemented, resulting in a favorable prognosis. CONCLUSIONS: These findings support the hypothesis that MRS is a systemic granulomatous disease caused by autoimmunity, which may also influence the occurrence and development of TMJ-OA through immune-related mechanisms. This study emphasizes the significance of systemic immune regulation in the treatment of patients with MRS and TMJ-OA comorbid conditions.


Assuntos
Síndrome de Melkersson-Rosenthal , Osteoartrite , Transtornos da Articulação Temporomandibular , Humanos , Síndrome de Melkersson-Rosenthal/complicações , Masculino , Adulto , Transtornos da Articulação Temporomandibular/etiologia , Transtornos da Articulação Temporomandibular/terapia , Osteoartrite/complicações , Osteoartrite/etiologia , Terapia Combinada
10.
Environ Monit Assess ; 196(9): 796, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112830

RESUMO

Investigations have revealed the presence of microplastics in both soil and groundwater, but the migration characteristics from soil to groundwater remain incompletely understood. In this study, two sampling sections consisting of soil-groundwater-river water were established near Lianxi Bridge and Xilin Bridge along the Jiuxi River in Xiamen. A total of 22 soil samples, 36 groundwater samples, and 18 river water samples were collected. Microplastics were detected in all samples with an abundance range of 392-836 n/kg in soil (mean, 655 ± 177 n/kg), 0.58-2.48 n/L groundwater (mean, 1.23 ± 0.42 n/L), and 0.38-1.80 n/L in river water (mean, 0.86 ± 0.41 n/L). Flakes predominantly constituted the shape of microplastics found in soil, while fibers dominated those present in water. Black, yellow, and red were the dominant color types. Polyamide (PA) and polyethylene (PE) were the main components of microplastics within soils, whereas polyethylene terephthalate (PET), polypropylene (PP), and PA prevailed within water. Microplastic particle sizes ranged from 39 to 2498 µm in soils, mainly from 29 to 3394 µm in water. The upstream section displayed higher abundances of microplastic compared to the downstream, revealing the soil particles having an intercepting effect on microplastics. The distribution and migration of microplastics in soil and groundwater are affected by many factors, including natural and anthropogenic factors, such as soil depth, soil properties, pore structure, hydrodynamics, hydraulic connections between groundwater and surface water, the extensive utilization and disposal of plastics, irrational exploitation of groundwater, and morphology and types of microplastics. These research findings contribute to a better understanding of the pathways, migration capacity, and influencing factors associated with microplastic entry into groundwater, thereby providing valuable technical support for the development of strategies aimed at controlling microplastic pollution.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Microplásticos , Poluentes do Solo , Solo , Poluentes Químicos da Água , Água Subterrânea/química , Poluentes Químicos da Água/análise , Microplásticos/análise , Poluentes do Solo/análise , Solo/química , Rios/química , China
11.
J Gastroenterol Hepatol ; 38(12): 2111-2121, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37787084

RESUMO

BACKGROUND AND AIM: Our prior research revealed that the tumor enhancement ratio (TER) on triphasic abdominal contrast-enhanced MDCT (CE-MDCT) scans was a prognostic factor for patients with stages I-III colon cancer. Building upon this finding, the present study aims to investigate the proteomic changes in colon cancer patients with varying TER values. METHODS: TER was analyzed on preoperative triphasic CE-MDCT scans of 160 stages I-III colon cancer patients. The survival outcomes of those in the low-TER and high-TER groups were compared. Proteomic analysis on colon cancer tissues was performed by mass spectrometry (MS) and verified by immune-histological chemistry (IHC) assays. In vivo, mouse xenograft models were employed to test the function of target proteins identified through the MS. CE-MDCT scans were conducted on mice xenografts, and the TER values were compared. RESULTS: Patients in the high-TER group had a significantly worse prognosis than those in the low-TER group. Proteomic analysis of colon cancer tissues revealed 153 differentially expressed proteins between the two groups. A correlation between TER and the abundance of α-SMA protein in tumor tissue was observed. IHC assays further confirmed that α-SMA protein expression was significantly increased in high-TER colon cancer, predominantly in cancer-associated fibroblasts (CAFs) within the cancer stroma. Moreover, CAFs promoted the growth of CRC xenografts in vivo and increased TER. CONCLUSIONS: Our study identified the distinct protein changes in colon cancer with low and high TER for the first time. The presence of CAFs may promote the growth of colon cancer and contribute to an increased TER.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias do Colo , Humanos , Animais , Camundongos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Tomografia Computadorizada Multidetectores/métodos , Proteômica/métodos , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/metabolismo , Prognóstico
12.
Pacing Clin Electrophysiol ; 46(5): 409-413, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36402128

RESUMO

Atrioesophageal fistula (AEF) is a rare but devastating complication of radiofrequency ablation (RFCA) for atrial fibrillation (AF) and is associated with high mortality rates. Whereas most cases of AEF are treated by emergency surgical interventions, we report a case of paroxysmal AF with AEF after combined therapy of catheter ablation and percutaneous left atrial appendage closure (LAAC), which was treated successfuly without major surgery or esophageal stenting. He was presented 18 days after the procedure, suffering chest pain, fever, and a transient loss of consciousness. Computed tomography (CT) of the chest disclosed a small accumulation of air in the region of the left atrium adjacent to the esophagus, suggesting AEF. Supported by early aggressive antibiotic therapy, pericardial drainage and a fasting state with adequate parenteral nutrition, resulted in improvement of his condition with no recurrence of symptoms. Subsequent chest CT scans confirmed disappearance of the leaked air and the patient was discharged home 28 days after admission with no neurological compromise. Early detection, rapid treatment and constant awareness of potential fatal consequences are prerequisites for successful treatment of this complication and prevention of fatal outcome.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Fístula Esofágica , Masculino , Humanos , Apêndice Atrial/cirurgia , Fístula Esofágica/etiologia , Fístula Esofágica/terapia , Átrios do Coração , Ablação por Cateter/efeitos adversos
13.
Nucleic Acids Res ; 49(4): 1972-1986, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33503260

RESUMO

Maintenance of stem-cell identity requires proper regulation of enhancer activity. Both transcription factors OCT4/SOX2/NANOG and histone methyltransferase complexes MLL/SET1 were shown to regulate enhancer activity, but how they are regulated in embryonic stem cells (ESCs) remains further studies. Here, we report a transcription factor BACH1, which directly interacts with OCT4/SOX2/NANOG (OSN) and MLL/SET1 methyltransferase complexes and maintains pluripotency in mouse ESCs (mESCs). BTB domain and bZIP domain of BACH1 are required for these interactions and pluripotency maintenance. Loss of BACH1 reduced the interaction between NANOG and MLL1/SET1 complexes, and decreased their occupancy on chromatin, and further decreased H3 lysine 4 trimethylation (H3K4me3) level on gene promoters and (super-) enhancers, leading to decreased enhancer activity and transcription activity, especially on stemness-related genes. Moreover, BACH1 recruited NANOG through chromatin looping and regulated remote NANOG binding, fine-tuning enhancer-promoter activity and gene expression. Collectively, these observations suggest that BACH1 maintains pluripotency in ESCs by recruiting NANOG and MLL/SET1 complexes to chromatin and maintaining the trimethylated state of H3K4 and enhancer-promoter activity, especially on stemness-related genes.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Células-Tronco Embrionárias/metabolismo , Elementos Facilitadores Genéticos , Histona-Lisina N-Metiltransferase/metabolismo , Proteína Homeobox Nanog/metabolismo , Regiões Promotoras Genéticas , Animais , Fatores de Transcrição de Zíper de Leucina Básica/química , Fatores de Transcrição de Zíper de Leucina Básica/fisiologia , Linhagem Celular , Células Cultivadas , Cromatina/metabolismo , Histonas/metabolismo , Camundongos , Fator 3 de Transcrição de Octâmero/metabolismo , Domínios Proteicos , Fatores de Transcrição SOXB1/metabolismo
14.
Pediatr Radiol ; 53(2): 332-336, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36018348

RESUMO

Chest radiography is commonly performed as a diagnostic tool of neonatal diseases. Contact-based radiation personal protective equipment (RPPE) has been widely used for radiation protection, but it does not provide full body protection and it is often shared between users, which has become a major concern during the coronavirus disease 2019 (COVID-19) pandemic. To address these issues, we developed a novel trolley to protect radiographers against X-ray radiation by reducing scatter radiation during neonatal radiographic examinations. We measured the scatter radiation doses from a standard neonatal chest radiograph to the radiosensitive organs using a phantom operator in three protection scenarios (trolley, radiation personal protective equipment [RPPE], no protection) and at three distances. The results showed that the scatter radiation surface doses were significantly reduced when using the trolley compared with RPPE and with no protection at a short distance (P<0.05 for both scenarios in all radiosensitive organs). The novel protective trolley provides a non-contact protective tool for radiographers against the hazard of scatter radiation during neonatal radiography examinations.


Assuntos
COVID-19 , Recém-Nascido , Humanos , Doses de Radiação , Radiografia , Raios X , Imagens de Fantasmas
15.
Acta Neurochir (Wien) ; 165(3): 613-623, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36595057

RESUMO

BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) bypass is a common surgery in treating moyamoya disease (MMD) with occluded MCA. Computational fluid dynamics (CFD) simulation might provide a simple, non-invasive, and low-cost tool to evaluate the efficacy of STA-MCA surgery. AIM: We aim to quantitatively investigate the treatment efficacy of STA-MCA surgery in improving the blood flow of MMD patients using CFD simulation. METHODS: This retrospective study included 11 MMD patients with occlusion around proximal MCA who underwent STA-MCA bypass surgery. CFD simulation was performed using patient-specific blood pressure and postoperative artery geometry. The volumetric flow rates of STA and the bypass, average flow velocity in the proximal segment of transcranial bypass, transcranial pressure drop, and transcranial flow resistance were measured and compared with a postoperative increment of cerebral blood flow (CBF) in MCA territories derived from perfusion imaging. Per-branch pressure drop from model inlet to bypass branch outlet was calculated. RESULTS: The volumetric flow rates of STA and the bypass were 80.84 ± 14.54 mL/min and 46.03 ± 4.21 mL/min. Average flow velocity in proximal bypass, transcranial pressure drop, and transcranial flow resistance were 0.19 ± 0.07 m/s, 3.72 ± 3.10 mmHg, and 6.54 ± 5.65 10-8 Pa s m-3. Postoperative mean increment of CBF in MCA territories was 16.03 ± 11.72 mL·100 g-1·min-1. Per-branch pressure drop was 10.96 ± 5.59 mmHg and 7.26 ± 4.25 mmHg in branches with and without stenosis. CONCLUSIONS: CFD simulation results are consistent with CBF observation in verifying the efficacy of STA-MCA bypass, where postoperative stenosis may influence the hemodynamics.


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Humanos , Doença de Moyamoya/cirurgia , Projetos Piloto , Artéria Cerebral Média/cirurgia , Artérias Temporais/cirurgia , Estudos Retrospectivos , Constrição Patológica , Revascularização Cerebral/métodos , Hemodinâmica , Circulação Cerebrovascular , Simulação por Computador , Imagem de Perfusão
16.
Zhongguo Zhong Yao Za Zhi ; 48(24): 6711-6720, 2023 Dec.
Artigo em Zh | MEDLINE | ID: mdl-38212031

RESUMO

This study investigated the mechanism of action of Scutellariae Radix-Coptidis Rhizoma(SR-CR) in intervening in non-alcoholic fatty liver disease(NAFLD) in rats based on lipidomics. Thirty-six SD rats were divided into a control group, a model group, SR-CR groups of different doses, and a simvastatin group, with six rats in each group. Rats in the control group were fed on a normal diet, while those in the remaining groups were fed on a high-lipid diet. After four weeks of feeding, drug treatment was carried out and rats were sacrificed after 12 weeks. Serum liver function and lipid indexes were detected using kits, and the pathomorphology of liver tissues was evaluated by hematoxylin-eosin(HE) staining and oil red O staining. Changes in lipid levels in rats were detected using the LC-MS technique. Differential lipid metabolites were screened by multivariate statistical analysis, and lipid metabolic pathways were plotted. The changes in lipid-related protein levels were further verified by Western blot. The results showed that compared with the control group, the model group showed increased levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.01), and decreased levels of γ-glutamyl transferase(γ-GT) and high-density lipoprotein cholesterol(HDL-c)(P<0.01), which were significantly recovered by the intervention of SR-CR. HE staining and oil red O staining showed that different doses of SR-CR could reverse the steatosis in the rat liver in a dose-dependent manner. After lipidomics analysis, there were significant differences in lipid metabolism between the model group and the control group, with 54 lipids significantly altered, mainly including glycerolipids, phosphatidylcholine, and sphingolipids. After administration, 44 differential lipids tended to normal levels, which indicated that SR-CR groups of different doses significantly improved the lipid metabolism level in NAFLD rats. Western blot showed that SR-CR significantly decreased TG-synthesis enzyme 1(DGAT1), recombinant lipin 1(LPIN1), fatty acid synthase(FASN), acetyl-CoA carboxylase 1(ACC1), and increased the phosphorylation level of ACC1. These changes significantly decreased the synthesis of TG and increased the rate of its decomposition, which enhanced the level of lipid metabolism in the body and finally achieved the lipid-lowering effect. SR-CR can improve NAFLD by inhibiting the synthesis of fatty acids and TG.


Assuntos
Compostos Azo , Medicamentos de Ervas Chinesas , Hepatopatia Gordurosa não Alcoólica , Ratos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Scutellaria baicalensis , Medicamentos de Ervas Chinesas/uso terapêutico , Preparações Farmacêuticas , Ratos Sprague-Dawley , Fígado , Triglicerídeos/metabolismo , Colesterol , Dieta Hiperlipídica
17.
BMC Plant Biol ; 22(1): 163, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365083

RESUMO

BACKGROUND: The rhizome of Polygonatum kingianum Coll. et Hemsl (P. kingianum) is a crucial traditional Chinese medicine, but severe bud dormancy occurs during early rhizome development. Low temperature is a positive factor affecting dormancy release, whereas the variation in carbohydrates during dormancy release has not been investigated systematically. Therefore, the sugar content, related metabolic pathways and gene co-expression were analysed to elucidate the regulatory mechanism of carbohydrates during dormancy release in the P. kingianum rhizome bud. RESULTS: During dormancy transition, starch and sucrose (Suc) exhibited opposing trends in the P. kingianum rhizome bud, representing a critical indicator of dormancy release. Galactose (Gal) and raffinose (Raf) were increased in content and synthesis. Glucose (Glc), cellulose (Cel), mannose (Man), arabinose (Ara), rhamnose (Rha) and stachyose (Sta) showed various changes, indicating their different roles in breaking rhizome bud dormancy in P. kingianum. At the beginning of dormancy release, Glc metabolism may be dominated by anaerobic oxidation (glycolysis followed by ethanol fermentation). After entering the S3 stage, the tricarboxylic acid cycle (TCA) and pentose phosphate pathway (PPP) were may be more active possibly. In the gene co-expression network comprising carbohydrates and hormones, HYD1 was identified as a hub gene, and numerous interactions centred on STS/SUS were also observed, suggesting the essential role of brassinosteroids (BRs), Raf and Suc in the regulatory network. CONCLUSION: We revealed cold-responsive genes related to carbohydrate metabolism, suggesting regulatory mechanisms of sugar during dormancy release in the P. kingianum rhizome bud. Additionally, gene co-expression analysis revealed possible interactions between sugar and hormone signalling, providing new insight into the dormancy release mechanism in P. kingianum rhizome buds.


Assuntos
Polygonatum , Regulação da Expressão Gênica de Plantas , Humanos , Dormência de Plantas/genética , Proteínas de Plantas/genética , Polygonatum/genética , Polygonatum/metabolismo , Rizoma/metabolismo , Açúcares
18.
J Neurol Neurosurg Psychiatry ; 93(4): 351-359, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34872980

RESUMO

OBJECTIVE: To assess (1) the association between atrial cardiopathy (AC) and non-stenotic intracranial complicated atherosclerotic plaque (NICAP) in patients with embolic stroke of undetermined source (ESUS) or small-vessel disease (SVD), and (2) the performance of previously proposed biomarkers to identify AC as the underlying aetiology in ESUS. METHODS: Based on our high-resolution MRI (HR-MRI) cohort, 403 subjects (243 ESUS and 160 SVD) were enrolled in the final analysis. All patients underwent intracranial HR-MRI to assess the presence of ipsilateral NICAP. Biomarkers of AC (ie, P-wave terminal force in lead V1 (PTFV1) on ECG, N-terminal probrain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T and left atrial diameter) were collected within 24 hours after admission. RESULTS: Among patients without ipsilateral NICAP, we found an association between the presence of AC (adjusted OR (aOR): 4.76, 95% CI 2.48 to 9.14), increased PTFV1 (aOR: 5.70, 95% CI: 2.43 to 13.39) and NT-proBNP (aOR: 1.65, 95% CI: 1.16 to 2.35) with ESUS. This association was not evident among patients with ipsilateral NICAP. The discrimination between ESUS versus SVD by AC/AC-related biomarkers was significantly improved after excluding ipsilateral NICAP. Similarly, the discrimination between ESUS and SVD by ipsilateral NICAP was notably augmented after excluding AC, PTFV1 and NT-proBNP. INTERPRETATION: AC is more prevalent in patients who had ESUS without ipsilateral NICAP compared with patients with, implying that AC and ipsilateral NICAP are two distinct, competing aetiologies of ESUS. Among the AC biomarkers studied in this analysis, PTFV1 seems to be the most informative.


Assuntos
AVC Embólico , Cardiopatias , Embolia Intracraniana , Placa Aterosclerótica , Acidente Vascular Cerebral , Biomarcadores , AVC Embólico/etiologia , Cardiopatias/complicações , Cardiopatias/diagnóstico por imagem , Humanos , Embolia Intracraniana/complicações , Embolia Intracraniana/diagnóstico por imagem , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem
19.
Pharmacol Res ; 182: 106314, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35718244

RESUMO

In this review, the global contribution of tradition Chinese medicine will be debriefed. The underlying obstacles and limitations for TCM development and modernization will be summarized and analyzed accordingly. Statistics data and corresponding reasons will be presented to illustrate the very laborious progression of TCM globalization. Several innovative strategies and advanced technologies will be advised in the review in the hope of fully facilitating and accelerating TCM's expansion into the global markets.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/uso terapêutico , Internacionalidade
20.
Org Biomol Chem ; 20(43): 8420-8424, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36285714

RESUMO

Unsymmetrical hybrid chiral diphosphorus ligands bearing a spirocyclic phosphoramidite scaffold have been developed and successfully applied in the iridium-catalyzed asymmetric hydrogenation of imines. With this newly developed chiral iridium catalytic system, a wide range of imines including sterically hindered ones could be hydrogenated to give the corresponding optically active amines in high yields (up to >99%) and with excellent enantioselectivities (up to >99% ee). The utility of this hydrogenation has been demonstrated by the preparation of the chiral fungicide (S)-benalaxyl.


Assuntos
Iminas , Irídio , Hidrogenação , Ligantes , Estereoisomerismo , Catálise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA