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1.
Gastrointest Endosc ; 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38583542

RESUMEN

BACKGROUND AND AIMS: The duodenal papillae are the primary and essential pathway for ERCP, greatly determining its complexity and outcome. We investigated the association between papilla morphology and post-ERCP pancreatitis (PEP) and constructed a robust model for PEP prediction. METHODS: We retrospectively enrolled patients who underwent ERCP in 2 centers from January 2019 to June 2022. Radiomic features of the papilla were extracted from endoscopic images with deep learning. Potential predictors and their importance were evaluated with 3 machine learning algorithms. A predictive model was developed using best subset selection by logistic regression, and its performance was evaluated in terms of discrimination, calibration, and clinical utility based on the area under curve (AUC) of the receiver-operating characteristic curve, calibration curve, and clinical decision curve, respectively. RESULTS: From 2 centers, 2038 and 334 ERCP patients were enrolled in this study with PEP rates of 7.9% and 9.6%, respectively. The radiomic score was significantly associated with PEP and showed great diagnostic value (AUC, .755-.821). Six hub predictors were selected to conduct a predictive model. The radiomics-based model demonstrated excellent discrimination (AUC, .825-.857) and therapeutic benefits in the training, testing, and validation cohorts. The addition of the radiomic score significantly improved the diagnostic accuracy of the predictive model (net reclassification improvement, .151-.583 [P < .05]; integrated discrimination improvement, .097-.235 [P < .001]). CONCLUSIONS: The radiomic signature of the papilla is a crucial independent predictor of PEP. The papilla radiomics-based model performs well for the clinical prediction of PEP.

2.
BMC Cardiovasc Disord ; 24(1): 82, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38297207

RESUMEN

BACKGROUND: Pathological cardiac hypertrophy is associated with cardiac dysfunction and is a key risk factor for heart failure and even sudden death. This study investigates the function of Mycn in cardiac hypertrophy and explores the interacting molecules. METHODS: A mouse model of cardiac hypertrophy was induced by isoproterenol (ISO). The cardiac dysfunction was assessed by the heart weight-to-body weight ratio (HW/BW), echocardiography assessment, pathological staining, biomarker detection, and cell apoptosis. Transcriptome alteration in cardiac hypertrophy was analyzed by bioinformatics analysis. Gain- or loss-of-function studies of MYCN proto-oncogene (Mycn), ubiquitin specific peptidase 2 (USP2), and junction plakoglobin (JUP) were performed. The biological functions of Mycn were further examined in ISO-treated cardiomyocytes. The molecular interactions were verified by luciferase assay or immunoprecipitation assays. RESULTS: Mycn was poorly expressed in ISO-treated mice, and its upregulation reduced HW/BW, cell surface area, oxidative stress, and inflammation while improving cardiac function of mice. It also reduced apoptosis of cardiomyocytes in mice and those in vitro induced by ISO. Mycn bound to the USP2 promoter to activate its transcription. USP2 overexpression exerted similar myocardial protective functions. It stabilized JUP protein by deubiquitination modification, which blocked the Akt/ß-catenin pathway. Knockdown of JUP restored phosphorylation of Akt and ß-catenin protein level, which negated the protective effects of USP2. CONCLUSION: This study demonstrates that Mycn activates USP2 transcription, which mediates ubiquitination and protein stabilization of JUP, thus inactivating the Akt/ß-catenin axis and alleviating cardiac hypertrophy-induced heart failure.


Asunto(s)
Insuficiencia Cardíaca , Proteína Proto-Oncogénica N-Myc , Animales , Ratones , beta Catenina/genética , beta Catenina/metabolismo , Cardiomegalia/genética , Cardiomegalia/prevención & control , gamma Catenina/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/prevención & control , Isoproterenol , Miocitos Cardíacos/metabolismo , Proteína Proto-Oncogénica N-Myc/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal
3.
Int Orthop ; 48(7): 1831-1838, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38558192

RESUMEN

PURPOSE: This study aims to explore the clinical value of autogenous tibial periosteal bone grafting in the treatment of osteochondral lesions of the talus (OLT) and analyze the three-dimensional factors in the necrotic zone of the talus. METHODS: A retrospective analysis was performed on 36 patients who underwent autogenous tibial periosteal bone grafting in the Foot and Ankle Surgery Department of our hospital between September 2018 and September 2022. The American Orthopaedic Foot and Ankle Society (AOFAS), Visual Analogue Scale (VAS), and Chinese Short-Form 36 Health Survey (SF-36) were used to evaluate treatment efficacy prior to surgery and at the last follow-up. Furthermore, Mimics 21.0 software was employed to measure the three-dimensional data of the necrotic area, including surface area, volume, and depth, in order to investigate their potential impact on patient prognosis. RESULTS: Among the 36 OLT patients who obtained complete follow-up, there were 22 males and 14 females. No complications such as surgical site infection, non-union of cartilage, post-traumatic arthritis, or donor site pain were observed. The AOFAS, VAS, and Chinese SF-36 scores of all patients at the last follow-up showed significant improvement compared to preoperative values. There was no significant correlation between the AOFAS, VAS, and Chinese SF-36 scores at the last follow-up and the depth, surface area, and volume of the necrotic zone. CONCLUSION: The use of autogenous tibial periosteal bone grafting can safely and effectively treat Hepple V OLT. Additionally, there is no significant correlation between the three-dimensional factors of the necrotic area and the prognosis of the patients.


Asunto(s)
Trasplante Óseo , Astrágalo , Tibia , Humanos , Masculino , Femenino , Astrágalo/cirugía , Adulto , Estudios Retrospectivos , Trasplante Óseo/métodos , Tibia/cirugía , Persona de Mediana Edad , Adulto Joven , Resultado del Tratamiento , Periostio/trasplante , Adolescente , Trasplante Autólogo/métodos , Necrosis , Imagenología Tridimensional
4.
BMC Cardiovasc Disord ; 22(1): 112, 2022 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-35300595

RESUMEN

BACKGROUND: To explore the effect of initial surgery for type I and II pulmonary atresia with intact ventricular septum (PA/IVS). METHODS: 50 children with type I PA/IVS and 50 with type II PA/IVS who had undergone initial surgery were enrolled. Children with Type I were divided into groups A (n = 25) and B (n = 25). Group A had received BT shunt combined with PDA ligation and balloon dilatation of pulmonary valve, whereas group B had undergone BT shunt combined with PDA ligation and pulmonary valve incision. Children with type II were divided into groups C (n = 25) and D (n = 25). Group C had received BT shunt combined with PDA ligation, right ventricular outflow tract (RVOT) incision and transannular patch. Group D had undergone BT shunt combined with PDA ligation, RVOT incision, transannular patch and artificial pulmonary valve implantation. The differences in mechanical ventilation time, length of ICU stay, mortality rate, tricuspid Z value, tricuspid regurgitation, oxygen saturation, pulmonary regurgitation, McGoon ratio, pulmonary artery transvalvular pressure, survival rate were compared between groups A and B, between groups C and D respectively. RESULTS: The ventilator assistance time and length of ICU stay were greater in group C than in group D (80.96 ± 8.42 h vs. 65.16 ± 4.85 h, P = 0.045; 222.00 ± 11.72 h vs. 162.48 ± 7.91 h, P = 0.048). The pulmonary artery transvalvular pressure was significantly higher in group A than in group B at 3, 6, 12, 24 and 36 months after surgery (64.86 ± 4.13 mmHg vs. 53.04 ± 5.64 mmHg, P = 0.045; 69.47 ± 1.93 mmHg vs. 55.95 ± 4.04 mmHg, P = 0.005; 80.16 ± 3.76 mmHg vs. 73.24 ± 2.34 mmHg, P = 0.035; 62.95 ± 5.64 mmHg vs. 48.47 ± 7.44 mmHg, P = 0.04; 53.69 ± 4.89 vs. 45.77 ± 3.26, P = 0.02). Furthermore, the tricuspid Z value was significantly greater in group B than in group A at 3 and 24 months after surgery (- (1.37 ± 0.04) vs. - (1.43 ± 0.06), P = 0.03; - (0.41 ± 0.06) vs. - (0.51 ± 0.11), P = 0.02). CONCLUSIONS: The effect of BT shunt combined with PDA ligation and pulmonary valve incision is superior to BT shunt combined with PDA ligation and balloon dilatation of pulmonary valve, and the effect of BT shunt combined with PDA ligation, RVOT incision, transannular patch and artificial pulmonary valve implantation is superior to BT shunt combined with PDA ligation, RVOT incision and transannular patch.


Asunto(s)
Cardiopatías Congénitas , Atresia Pulmonar , Insuficiencia de la Válvula Pulmonar , Válvula Pulmonar , Niño , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , Humanos , Lactante , Atresia Pulmonar/diagnóstico por imagen , Atresia Pulmonar/cirugía , Válvula Pulmonar/diagnóstico por imagen , Válvula Pulmonar/cirugía , Resultado del Tratamiento
5.
BMC Cardiovasc Disord ; 22(1): 182, 2022 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-35439934

RESUMEN

BACKGROUND: Heart disease is a major cause of mortality in developed countries. The associated pathology is mainly characterized by the loss of cardiomyocytes that contributes to heart failure (HF). This study aims to investigate the mechanism of euchromatic histone lysine methyltransferase 2 (EHMT2, also term G9a) in HF in rats. METHODS: Differentially expressed mRNAs in HF were screened using GEO database. Sera from subjects with or without HF were collected, and PCR was performed to detect the G9a expression. G9a was downregulated in cardiomyocytes exposed to oxygen-glucose deprivation (OGD), followed by CCK8, flow cytometry, colorimetric method, and western blot assays. Established HF rats were delivered with lentiviral vectors carrying sh-G9a, and TTC staining, HE staining, TUNEL, ELISA, and western blot were performed. The regulation of G9a on the downstream target BDNF was investigated by RT-qPCR, Western blot, and ChIP-qPCR. Finally, rescue experiments were carried out to substantiate the effect of G9a on cardiomyocyte apoptosis and injury via the BDNF/TrkB axis. RESULTS: G9a was overexpressed, whereas BDNF was downregulated in HF. Knockdown of G9a inhibited apoptosis and injury in OGD-treated cardiomyocytes and attenuated the extent of HF and myocardial injury in rats. Silencing of G9a promoted BDNF transcription by repressing H3K9me2 modification of the BDNF promoter. Further depletion of BDNF partially reversed the effect of sh-G9a in alleviating cardiomyocyte apoptosis and injury by inhibiting the TrkB signaling pathway. CONCLUSION: G9a inhibits BDNF expression through H3K9me2 modification, thereby impairing the TrkB signaling pathway and exacerbating the development of HF.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Insuficiencia Cardíaca , Animales , Apoptosis , Factor Neurotrófico Derivado del Encéfalo/genética , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Antígenos de Histocompatibilidad/genética , Antígenos de Histocompatibilidad/metabolismo , Antígenos de Histocompatibilidad/farmacología , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Miocitos Cardíacos/metabolismo , Ratas
6.
BMC Pulm Med ; 22(1): 234, 2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35710365

RESUMEN

BACKGROUND: The application of prone position (PP) in acute respiratory distress syndrome (ARDS) supported by venovenous extracorporeal membrane oxygenation (VV-ECMO) is controversial. OBJECTIVES: To evaluate the safety and efficacy of application of PP during VV-ECMO in patients with ARDS. METHODS: This was a single-center, retrospective study of patients who met the Berlin definition of ARDS, and were supported with VV-ECMO. We divided the patients into two groups. The prone group included patients who were supported by VV-ECMO, and experienced at least one period of PP, while those without PP during VV-ECMO were defined as the supine group. Propensity score matching (PSM) at a ratio of 1:1 was introduced to minimize potential confounders. The primary outcomes were the complications of PP and the change of arterial oxygen pressure/fraction of the inspiration (PaO2/FiO2) ratio after PP. The secondary outcomes were hospital survival, ICU survival, and ECMO weaning rate. RESULTS: From April 2013 to October 2020, a total of 91 patients met the diagnostic criteria of ARDS who were supported with ECMO. 38 patients (41.8%) received at least one period of PP during ECMO, while 53 patients (58.2%) were maintained in supine position during ECMO. 22 minor complications were reported in the prone group and major complications were not found. The other ECMO-related complications were similar between two groups. The PaO2/FiO2 ratio significantly improved after PP compared with before (174.50 (132.40-228.25) mmHg vs. 158.00 (122.93-210.33) mmHg, p < 0.001). PSM selected 25 pairs of patients with similar characteristics. Hospital survival or ICU survival did not differ between the two groups (40% vs. 28%, p = 0.370; 40% vs. 32%, p = 0.556). Significant difference of ECMO weaning rate between two groups was not found (56% vs. 32%, p = 0.087). CONCLUSIONS: PP during VV-ECMO was safe and could improve oxygenation. A large-scale and well-designed RCT is needed in the future.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Oxigenación por Membrana Extracorpórea/efectos adversos , Humanos , Posicionamiento del Paciente , Posición Prona , Síndrome de Dificultad Respiratoria/terapia , Estudios Retrospectivos
7.
J Clin Pharm Ther ; 47(10): 1608-1618, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35716048

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: The presence of extracorporeal membrane oxygenation (ECMO) is suggested to further exacerbate the pharmacokinetics (PK) alterations that occur during critical illness. The objectives of this study were to determine the population PK model of polymyxin B in critically ill patients with or without ECMO support investigated the influence of ECMO on PK variability and to identify an optimal dosing strategy. METHODS: Forty-four critically ill patients were enrolled, including eight patients with ECMO support. Eight serial serum samples were collected from each patient at steady state. The population PK was determined using NONMEM and Monte Carlo simulation was performed to evaluate the exposures of different dosing regimens. RESULTS: The PK analyses included 342 steady-state concentrations and a two-compartment model was optimal for polymyxin B PK data modelling. In the final model, creatinine clearance (CLCR ) was the significant covariate on CL (typical value 1.27 L/h; between-subject variability 15.1%) and ECMO did not show a significant impact on the polymyxin B PK. Additionally, we found that the PK parameter estimates of patients with and without ECMO support were mostly similar. Based on Monte Carlo simulations, the dose escalation of polymyxin B in patients with increased CLCR improved the probability of achieving required exposure. For patients with CLCR ≤ 120 ml/min, a dosage regimen of 100 mg every 12 h may represent the optimal regimen at an MIC of 1 mg/L. WHAT IS NEW AND CONCLUSION: The impact of ECMO on the polymyxin B PK is likely to be minimal. Our study showed a potential relationship between CLCR and polymyxin B CL, and the dose of polymyxin B should be adjusted in patients with increased CLCR .


Asunto(s)
Enfermedad Crítica , Oxigenación por Membrana Extracorpórea , Antibacterianos , Creatinina , Humanos , Pruebas de Sensibilidad Microbiana , Polimixina B
8.
Ecotoxicol Environ Saf ; 241: 113758, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35716408

RESUMEN

Silicosis is a fibrotic disease caused by long-term inhalation of SiO2 particles that currently has no effective treatment. Earlier studies have suggested that pulmonary lymphatic vessels play a key role in the transport of silica but have not address the long-term effects of altered pulmonary lymphatic drainage on silicosis. Here, we investigated the impact of impaired pulmonary lymphatic drainage on silicosis. In the past, lymphatic drainage disorders were established mainly through the use of VEGF inhibitors. For the first time, we established a model of pulmonary lymphatic drainage disorder by ligating the thoracic duct in rats. Impaired pulmonary lymphatic drainage was found to aggravate inflammation and oxidative damage in silicosis rats and accelerate silicosis progression. Next, we investigated the effect of pulmonary lymphatic drainage on silicosis. We have demonstrated the effect of sodium tanshinone IIA sulfonate(STS) on lymphangiogenesis, which revealed that STS promotes lymphangiogenesis and can delay inflammation, oxidative damage, and fibrosis progression in silicosis rats by promoting the pulmonary lymphatic drainage response, and this effect is mediated by the VEGFR-3/PI3K/AKT signaling pathway. These findings suggest that pulmonary lymphogenesis plays an important role in silicosis pathogenesis, and targeted intervention in pulmonary lymphangiogenesis may be a potential strategy for treating of silicosis in the future.


Asunto(s)
Vasos Linfáticos , Silicosis , Animales , Fibrosis , Inflamación/patología , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patología , Fosfatidilinositol 3-Quinasas , Ratas , Dióxido de Silicio/toxicidad , Silicosis/metabolismo
9.
Anal Chem ; 93(48): 16175-16183, 2021 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-34806872

RESUMEN

Design and construction of a membrane that can achieve selective separation of uranium from spent fuel or seawater is a big challenge in the field of separation science. In this work, 1,3,5-benzenetricarboxylic acid (BTC) and three different nitrates (Zn/Ni/Cu) were used to prepare metal-organic frameworks (BTC-MOFs) with different pore sizes, and then, BTC-MOFs were intercalated into the interlayers of graphene oxide (GO) for preparing the composite membranes which presented selective separation of uranium with strong acid resistance. Composite membranes prepared by Zn/Ni/Cu-BTC-MOFs and GO can achieve the separation between ions of different valence states, and their permeability and selectivity depend on the membrane thickness, the acidity of driving solution, and the pore sizes of MOFs. Importantly, Cu-BTC-MOF-intercalated GO membranes can not only achieve the selective separation of Th4+ and UO22+ with a selectivity of ≈6 but also induce the ultra-high selectively separation of UO22+ and Ce3+ because the rejection rate of Ce3+ is about 100%. Moreover, the Zn-BTC-MOF-intercalated GO membrane shows an excellent selectivity of Th4+ and UO22+ with a selectivity of ≈25, and it may also achieve selective separation of uranium from seawater.

10.
Exp Cell Res ; 393(1): 112059, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32380038

RESUMEN

F-box and WD repeat domain-containing 7 (FBXW7) is an E3-ubiquitin ligase, which serves as one of the components of the SKP1, CUL1, and F-box protein type ubiquitin ligase (SCF) complex. Previous studies reveal that FBXW7 participates in cancer, inflammation and Parkinson's disease. FBXW7 also contributes to angiogenesis of endothelial cells. However, the function of FBXW7 in cardiac homeostasis remains to elucidate. Here we identified the critical role of FBXW7 during cardiac hypertrophy in humans and rodents. Quantitative real-time PCR (qRT-PCR) and Western blot revealed that the mRNA and protein levels of FBXW7 were upregulated significantly in hypertrophic hearts in human and mouse as well as Angiotensin II (Ang II)-induced hypertrophic neonatal rat cardiomyocytes (NRCM). Gain-of-function (adenovirus) and loss-of-function (siRNA) experiments provided evidence that FBXW7 promoted Ang II-induced cardiomyocyte hypertrophy as demonstrated by the increase in the size of cardiomyocytes and overexpression of hypertrophic fetal genes myosin heavy chain 7 (Myh7) natriuretic peptide a (Nppa), brain natriuretic peptide (Nppb). Further mechanism study revealed that FBXW7 promoted the expression of sine oculis homeobox homolog 1 (SIX1) in cardiomyocytes, which relied on regulation of the stability of the histone methyltransferase EZH2 (Enhancer of zeste homolog 2). Previous work revealed the pro-hypertrophic role of the EZH2-SIX1 axis in rodents. Indeed, our genetic and pharmacological evidence showed that the EZH2-SIX1 signaling was critically involved in FBXW7 functions in Ang II-induced cardiomyocyte hypertrophy. Therefore, we identified FBWX7 as an important regulator of cardiac hypertrophy via modulating the EZH2-SIX1 axis.


Asunto(s)
Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Animales , Cardiomegalia/patología , Células Endoteliales/metabolismo , Humanos , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Transducción de Señal
11.
Sheng Li Xue Bao ; 73(3): 423-432, 2021 Jun 25.
Artículo en Zh | MEDLINE | ID: mdl-34230944

RESUMEN

Chronic pain of knee osteoarthritis (KOA) greatly affects the quality of life and functional activities of patients. It is important to clarify the underlying mechanisms of KOA pain and the analgesic effect of different therapies. Neuroimaging technology has been widely used in the basic and clinical research of pain. In the recent years, neuroimaging technology has played an important role in the basic and clinical research of KOA pain. Increasing evidence demonstrates that chronic pain in KOA includes both nociceptive and neuropathic pain. The neuropathic mechanism involved in KOA pain is complex, which may be caused by peripheral or central sensitization. In this paper, we review the regional changes of brain pathophysiology caused by KOA pain based on magnetic resonance imaging (MRI), electroencephalogram (EEG), magnetoencephalogram (MEG), near-infrared spectroscopy (NIRS) and other neuroimaging techniques. We also discuss the central analgesic mechanism of different KOA therapies, with a focus on the latest achievements in the evaluation and prediction of pain. We hope to provide new thoughts for the treatment of KOA pain, especially in the early and middle stages of KOA.


Asunto(s)
Dolor Crónico , Osteoartritis de la Rodilla , Dolor Crónico/diagnóstico por imagen , Humanos , Neuroimagen , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/diagnóstico por imagen , Calidad de Vida , Tecnología
12.
Environ Res ; 190: 110014, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32768476

RESUMEN

Zeolite-Mg/Fe chloride dual enhanced coagulation is a cost-effective method for advanced treatment of swine wastewater, but the sludge generated after the enhanced coagulation remains to be a problem. In this study, the precipitate from a swine wastewater coagulation unit was regenerated by pyrolysis treatment in an O2-limited environment to develop a high efficient adsorbent (biochar-mineral composite, BMC) for the removal of Pb(II) from wastewater. SEM images indicate that complex Mg/Fe oxides and sludge biochar gathered around zeolite particles. Effects of different influencing factors such as Pb(II) initial concentration, pH, adsorption time and ion concentration on the adsorption performance were investigated. The results show that the Langmuir isotherm model can better express the adsorption of Pb(II) on BMC than Freundlich model and Temkin model. BMC pyrolyzed at 500 °C showed the maximum adsorption capacity of 450.58 mg/g under experimental condition of 25 °C, 100 mg/L Pb(II) initial concentration and the initial pH of 5.6. The adsorption mechanisms on BMC mainly include ion exchange, electrostatic interaction. Therefore, it is a cost-effective and environmental-friendly strategy to obtain biochar-mineral composite from recycled sludge, which can efficiently remove Pb(II) from wastewater.


Asunto(s)
Aguas Residuales , Contaminantes Químicos del Agua , Adsorción , Animales , Carbón Orgánico , Concentración de Iones de Hidrógeno , Cinética , Plomo , Minerales , Aguas del Alcantarillado , Porcinos , Contaminantes Químicos del Agua/análisis
13.
Adv Healthc Mater ; 13(3): e2302320, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37883686

RESUMEN

Sepsis is caused by a disordered host immune in response to infection and endothelial cells perform a crucial role in boosting immunity reaction in the pathophysiology of sepsis and septic organ failure. The aim of this study is to construct a novel erythrocyte membrane-derived nanosystems to reverse endothelial damage in sepsis. Herein, an innovative nanometer calcium metal-organic framework (Ca-MOF) is generated for the first time by using chelidonic acid as a ligand and calcium chloride as an ion donor for anti-inflammation. Then, zoliflodacin is loaded into Ca-MOF (CMZ) to sterilize and nanoscale erythrocyte membrane vesicles are prepared by modification with a γ3 peptide on the surface (γ3-RM) for precise targeting. Finally, γ3-RM camouflages the nanocore CMZ, to form novel erythrocyte membrane-camouflaged nanoparticle γ3-RCMZ. The superior performance of novel nanosystem results from its suitable biocompatibility, nontoxicity, specific targeting, and anti-inflammatory and bactericidal effects. Its anti-inflammatory mechanism mainly involves inhibiting the Caspase1-nuclear factor kappa-B (Caspase1-NF-κB) pathway and oxidative stress reduction to alleviate endothelial damage. Moreover, the findings have revealed for the first time that the bactericidal drug zoliflodacin also has anti-inflammatory effects in vivo and in vitro. Therefore, the novel nanosystem (γ3-RCMZ) provides a new nanotherapy strategy for sepsis treatment.


Asunto(s)
Barbitúricos , Membrana Eritrocítica , Isoxazoles , Morfolinas , Oxazolidinonas , Sepsis , Compuestos de Espiro , Humanos , Células Endoteliales/metabolismo , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , FN-kappa B/metabolismo , Antiinflamatorios/uso terapéutico
14.
Int J Pharm ; 661: 124378, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38925241

RESUMEN

Currently, to overcome the short half-life of the local anesthetic ropivacaine, drug delivery systems such as nanoparticles and liposomes have been used to prolong the analgesic effect, but they are prone to abrupt release from the site of administration or have poor slow-release effects, which increases the risk of cardiotoxicity. In this study, injectable lipid suspensions based on ropivacaine-docusate sodium hydrophobic ion pairing (HIP) were designed to significantly prolong the duration of analgesia. The resulting ion-paired lipid suspension (HIP/LIPO) had a micrometer scale and a high zeta potential, which facilitates stable in situ retention. The strong interaction between docusate sodium and ropivacaine was verified using thermal and spectroscopic analyses, and the formation of micron-sized polymorphic vesicles was attributed to the mutual stabilizing interactions between ropivacaine-docusate sodium HIP, docusate sodium and lecithin. The HIP/LIPO delivery system could maintain drug release for more than 5 days in vitro and achieve high analgesic efficacy for more than 10 days in vivo, reducing the side effects associated with high drug doses. The stable HIP/LIPO delivery system is a promising strategy that offers a clinically beneficial alternative for postoperative pain management and other diseases.

15.
Inflammation ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38867118

RESUMEN

Brahma-related gene 1 (BRG1) has been implicated in the repair of DNA double-strand breaks (DSBs). Downregulation of BRG1 impairs DSBs repair leading to accumulation of double-stranded DNA (dsDNA). Currently, the role of BRG1 in diabetic cardiomyopathy (DCM) has not been clarified. In this study, we aimed to explore the function and molecular by which BRG1 regulates DCM using mice and cell models. We found that BRG1 was downregulated in the cardiac tissues of DCM mice and in cardiomyocytes cultured with high glucose and palmitic acid (HG/PA), which was accompanied by accumulation of dsDNA and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. shRNA-mediated Brg1 knockdown aggravated DCM mice cardiac functions, enhanced dsDNA accumulation, cGAS-STING signaling activation, which induced inflammation and apoptosis. In addition, the results were further verified in HG/PA-treated primary neonatal rat cardiomyocytes (NRCMs). Overexpression of BRG1 in NRCMs yielded opposite results. Furthermore, a selective cGAS inhibitor RU.521 or STING inhibitor C-176 partially reversed the BRG1 knockdown-induced inflammation and apoptosis in vitro. In conclusion, our results demonstrate that BRG1 is downregulated during DCM in vivo and in vitro, resulting in cardiomyocyte inflammation and apoptosis due to dsDNA accumulation and cGAS-STING signaling activation. Therefore, targeting the BRG1-cGAS-STING pathway may represent a novel therapeutic strategy for improving cardiac function of patients with DCM.

16.
BMJ Open ; 14(6): e083440, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38866576

RESUMEN

INTRODUCTION: Knee osteoarthritis (KOA) is one of the most common osteoarthritis, imposing substantial economic and medical burdens on both individuals and society. In China, Tuina has been selected as a complementary and alternative therapy to relieve knee pain and dysfunction symptoms. However, the current evidence is insufficient to support the efficacy of Tuina therapy in addressing knee pain and improving physical function. The trial aims to compare the effectiveness of Tuina with celecoxib, which is considered as the standard treatment, and to assess its potential as an alternative therapy through changes in outcome measures. METHODS AND ANALYSIS: A total of 360 KOA patients aged between 40 and 70 years and classified as Kellgren and Lawrence grades I-II will be recruited from eight subcentral hospitals. The participants will be randomly assigned to either the treatment group (Tuina, Biw) or the control group (celecoxib, Qd), with both groups undergoing a 4-week intervention phase followed by an 8-week follow-up phase. The primary outcome is the change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at week 4 compared with baseline. Secondary outcomes including WOMAC stiffness and function subscales, WOMAC total score, 36-item Short-Form Health Survey, Timed Up and Go test, Short Physical Performance Battery, gait analysis parameters and pain medication records will be assessed at weeks 4, 8 and 12. Any adverse events that occur during the trial will be promptly recorded. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (2023SHL-KY-16-01, 2023SHL-KY-16-02). Written informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2300069416.


Asunto(s)
Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/terapia , China , Persona de Mediana Edad , Anciano , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Dimensión del Dolor , Femenino , Celecoxib/uso terapéutico , Estudios Multicéntricos como Asunto , Adulto , Resultado del Tratamiento , Artralgia/tratamiento farmacológico
17.
Environ Int ; 189: 108783, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38823156

RESUMEN

BACKGROUND: Temperature affects influenza transmission; however, currently, limited evidence exists about its effect in China at the national and city levels as well as how temperature can be integrated into influenza interventions. METHODS: Meteorological, pollutant, and influenza data from 201 cities in mainland China between 2013 and 2018 were analyzed at both the city and national levels to investigate the relationship between temperature and influenza prevalence. We examined the impact of temperature on the time-varying reproduction number (Rt) using generalized additive quasi-Poisson regression models combined with the distributed lag nonlinear model. Threshold temperatures were determined for seven regions based on the early warning threshold of serious influenza outbreaks, set at Rt = 1.2. A multivariate random-effects meta-analysis was employed to assess region-specific associations. The excess risk (ER) index was defined to investigate the correlation between Rt and temperature, modified based on seasonal and regional characteristics. RESULTS: At the national level and in the central, northern, northwestern, and southern regions, temperature was found to be negatively correlated with relative risk, whereas the shapes of the data curves for the eastern, southwestern, and northeastern regions were not well defined. Low temperatures had an observable effect on influenza prevalence; however, the effects of high temperatures were not obvious. At an Rt of 1.2, the threshold temperatures for reaching a warning for serious influenza outbreaks were - 24.3 °C in the northeastern region, 16.6 °C in the northwestern region, and between 1℃ and 10 °C in other regions. CONCLUSION: The study findings revealed that temperature had a varying effect on influenza transmission trends (Rt) across different regions in China. By identifying region-specific temperature thresholds at Rt = 1.2, more effective early warning systems for influenza outbreaks could be tailored. These findings emphasize the significance of the region-specific adaptation of influenza prevention and control measures.


Asunto(s)
Ciudades , Gripe Humana , Temperatura , China/epidemiología , Gripe Humana/epidemiología , Humanos , Ciudades/epidemiología , Prevalencia , Estaciones del Año
18.
Plants (Basel) ; 13(13)2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38999566

RESUMEN

As one of the most important food crops in the world, rice yield is directly related to national food security. Lodging is one of the most important factors restricting rice production, and the cultivation of rice varieties with lodging resistance is of great significance in rice breeding. The lodging resistance of rice is directly related to the mechanical strength of the stalks. In this paper, we reviewed the cell wall structure, its components, and its genetic regulatory mechanism, which improved the regulatory network of rice stalk mechanical strength. Meanwhile, we analyzed the new progress in genetic breeding and put forward some scientific problems that need to be solved in this field in order to provide theoretical support for the improvement and application of rice breeding.

19.
Cell Rep Med ; 5(3): 101429, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38378003

RESUMEN

Obesity is a risk factor for colorectal cancer (CRC), and the involvement of gut microbiota in the pathogenesis of obesity and CRC is widely recognized. However, the landscape of fecal microbiome and metabolome distinguishing patients with obesity-related CRC from obesity remains unknown. Here, we utilize metagenomic sequencing and metabolomics from 522 patients with CRC and healthy controls to identify the characteristics of obese CRC. Our integrated analysis reveals that obesity-related CRC is characterized by elevated Peptostreptococcus stomatis, dysregulated fatty acids and phospholipids, and altered Kyoto Encyclopedia of Genes and Genomes pathways involving glycerophospholipid metabolism and lipopolysaccharide synthesis. Correlation analysis unveils microbial interactions in obesity, where the probiotic Faecalibacterium prausnitzii and the tumor-promoting species P. stomatis may engage in cross-feeding, thereby promoting tumorigenesis. In vitro experiments affirm enhanced growth under cross-feeding conditions. The mutualistic microbe-microbe interaction may contribute to the association between obesity and elevated CRC risk. Additionally, diagnostic models incorporating BMI-specific microbial biomarkers display promise for precise CRC screening.


Asunto(s)
Neoplasias Colorrectales , Microbiota , Humanos , Metaboloma , Obesidad/metabolismo , Neoplasias Colorrectales/microbiología , Interacciones Microbianas
20.
Food Chem ; 447: 138964, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38461715

RESUMEN

Citrus peel is a commonly used food-medicine material in the production of fast-moving consumer goods (FMCGs). For instance, Ganpu tea is manufactured by combining the peel of Citri Reticulatae 'Chachi' (PCRC) with Pu-erh tea. The alleviated irritation of PCRC through years of aging makes Citri reticulatae Pericarpium a traditional Chinese medicine. Herein, we introduced short-term steaming into the processing of PCRC to favor the quick removal of its irritation while retaining its food-medicine properties. Sensory evaluation and volatile component analysis showed that 60-s steaming reduced irritation of freshly prepared PCRC. Biological evaluations indicated no effects of steaming on the neuroprotective activity of PCRC. The process increased the contents of several bioactive ingredients, including hesperidin, nobiletin, tangeretin, and synephrine. In addition, physical indications of accelerating PCRC aging were observed. Taken together, our findings suggest that short-term steaming may offer a promising new possibility for enhancing the quality of citrus peel.


Asunto(s)
Citrus , Medicamentos Herbarios Chinos , Medicina Tradicional China , Alimentos ,
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