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1.
J Cell Mol Med ; 28(14): e18541, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39046429

RESUMO

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with poor prognosis due to late recurrence and metastasis. Metastasis is an important prognostic factor of SS. This study aimed to identify the core genes and mechanisms associated with SS metastasis. Microarray data for GSE40021 and GSE40018 were obtained from the Gene Expression Omnibus database. 186 differentially expressed genes (DEGs) were identified. The biological functions and signalling pathways closely associated with SS metastasis included extracellular matrix (ECM) organization and ECM-receptor interaction. Gene set enrichment analysis showed that the terms cell cycle, DNA replication, homologous recombination and mismatch repair were significantly enriched in the metastasis group. Weighted gene co-expression network analysis identified the most relevant module and 133 hub genes, and 31 crossover genes were identified by combining DEGs. Subsequently, four characteristic genes, EXO1, NCAPG, POLQ and UHRF1, were identified as potential biomarkers associated with SS metastasis using the least absolute shrinkage and selection operator algorithm and validation dataset verification analysis. Immunohistochemistry results from our cohort of 49 patients revealed visible differences in the expression of characteristic genes between the non-metastatic and metastatic groups. Survival analysis indicated that high expression of characteristic genes predicted poor prognosis. Our data revealed that primary SS samples from patients who developed metastasis showed activated homologous recombination and mismatch repair compared to samples from patients without metastasis. Furthermore, EXO1, NCAPG, POLQ and UHRF1 were identified as potential candidate metastasis-associated genes. This study provides further research insights and helps explore the mechanisms of SS metastasis.


Assuntos
Biomarcadores Tumorais , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , Sarcoma Sinovial , Sarcoma Sinovial/genética , Sarcoma Sinovial/patologia , Sarcoma Sinovial/metabolismo , Humanos , Prognóstico , Biomarcadores Tumorais/genética , Redes Reguladoras de Genes , Feminino , Masculino , Bases de Dados Genéticas , Biologia Computacional/métodos , Pessoa de Meia-Idade
2.
Opt Express ; 32(8): 14876-14891, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859422

RESUMO

Visible light communication (VLC) can be integrated into a liquid crystal display (LCD) by modulating its backlight while normally showing pictures. Received by ordinary cameras, such integrated display and communication (IDAC) systems are promising for the Internet of Things and Metaverse. However, in the premise of unaffected display function, the capacity of current IDAC systems is limited, with data rates of very few kbps. This work proposes a new architecture: multiple-input, multiple-output (MIMO) VLC integrated into a mini-LED LCD, whose many backlight segments act as multiple transmitters. A camera utilizes the rolling shutter effect with independent pixel columns to form multiple outputs. The communication capacity is thus significantly multiplied by the backlight column number. In addition, local dimming, which is favorable for an LCD's contrast and power consumption, is exploited to achieve efficient signal modulation. We built a mini-LED LCD prototype with 8-by-20 backlight segments for experimental verification. The backlight segments multiplex a video-rate signal for local dimming and a high-frequency (∼34 kHz) signal modulated through multi-pulse position modulation (MPPM) for VLC. By taking photographs with a camera 1.1 m away from the screen, a record-high rate of 201.6 kbps (approximately ten times faster than current IDAC systems) was experimentally achieved with a bit error rate satisfying the forward error correction. Improved image contrast due to local dimming was also observed.

3.
Vet Res ; 55(1): 45, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589958

RESUMO

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus that causes acute watery diarrhea, vomiting, and dehydration in newborn piglets. The type III interferon (IFN-λ) response serves as the primary defense against viruses that replicate in intestinal epithelial cells. However, there is currently no information available on how SADS-CoV modulates the production of IFN-λ. In this study, we utilized IPI-FX cells (a cell line of porcine ileum epithelium) as an in vitro model to investigate the potential immune evasion strategies employed by SADS-CoV against the IFN-λ response. Our results showed that SADS-CoV infection suppressed the production of IFN-λ1 induced by poly(I:C). Through screening SADS-CoV-encoded proteins, nsp1, nsp5, nsp10, nsp12, nsp16, E, S1, and S2 were identified as antagonists of IFN-λ1 production. Specifically, SADS-CoV nsp1 impeded the activation of the IFN-λ1 promoter mediated by MAVS, TBK1, IKKε, and IRF1. Both SADS-CoV and nsp1 obstructed poly(I:C)-induced nuclear translocation of IRF1. Moreover, SADS-CoV nsp1 degraded IRF1 via the ubiquitin-mediated proteasome pathway without interacting with it. Overall, our study provides the first evidence that SADS-CoV inhibits the type III IFN response, shedding light on the molecular mechanisms employed by SADS-CoV to evade the host immune response.


Assuntos
Alphacoronavirus , Infecções por Coronavirus , Doenças dos Suínos , Animais , Suínos , Complexo de Endopeptidases do Proteassoma , Interferon lambda , Alphacoronavirus/fisiologia , Ubiquitinas , Infecções por Coronavirus/veterinária
4.
J Phys Chem A ; 128(30): 6286-6295, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39042908

RESUMO

The deliquescence phase transition of atmospheric aerosols is crucial for radiative forcing and atmospheric chemistry. However, the deliquescence kinetics of micrometer-sized aerosols, especially the formation and evolution of surface solution films, remain poorly understood. In this study, IR spectral characteristics were employed for the first time to quantify the solute concentration evolution in surface solution films. At a constant relative humidity (RH) of ∼65%, solution films on NaCl crystals exhibited a very low solute concentration (3.06 ± 0.18 mol/L), comparable to aqueous NaCl droplets above 90% RH. These films reached saturation at ∼74% RH, i.e., the deliquescence RH of NaCl, maintaining a nearly constant saturation level during deliquescence. In contrast, amorphous NaNO3 solids showed supersaturated solution films before deliquescence. Following deliquescence, the saturation level of solution phases increased due to faster solid dissolution rates than liquid water condensation. These findings address knowledge gaps in the complex nonequilibrium dissolution processes of crystalline or amorphous atmospheric aerosols.

5.
World J Surg Oncol ; 22(1): 120, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702816

RESUMO

BACKGROUND: REBOA is a method used to manage bleeding during surgery involving sacropelvic tumors. Nevertheless, studies on the use of REBOA among elderly people are lacking. The aim of this research was to investigate the efficacy and safety of Zone III REBOA in patients aged more than 70 years. METHODS: A comparative study was conducted using case-control methods. A group of patients, referred to as Group A, who were younger than 70 years was identified and paired with a comparable group of patients, known as Group B, who were older than 70 years. Continuous monitoring of physiological parameters was conducted, and blood samples were collected at consistent intervals. RESULTS: Totally, 188 participants were enrolled and received REBOA. Among the 188 patients, seventeen were aged more than 70 years. By implementing REBOA, the average amount of blood loss was only 1427 ml. Experiments were also conducted to compare Group A and Group B. No notable differences were observed in terms of demographic variables, systolic blood pressure (SBP), arterial pH, lactate levels, blood creatinine levels, potassium levels, or calcium levels at baseline. Additionally, after the deflation of the REBOA, laboratory test results, which included arterial pH, lactate, potassium concentration, calcium concentration, and blood creatinine concentration, were not significantly different (P > 0.05). CONCLUSION: This study indicated that in selected patients aged more than 70 years can achieve satisfactory hemodynamic and metabolic stability with Zone III REBOA. LEVEL OF EVIDENCE: Therapeutic study, Level III.


Assuntos
Neoplasias Pélvicas , Humanos , Feminino , Masculino , Idoso , Estudos de Casos e Controles , Pessoa de Meia-Idade , Neoplasias Pélvicas/cirurgia , Neoplasias Pélvicas/patologia , Seguimentos , Prognóstico , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Perda Sanguínea Cirúrgica/prevenção & controle , Idoso de 80 Anos ou mais , Adulto
6.
Opt Express ; 31(4): 6262-6280, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36823887

RESUMO

Vision-correcting near-eye displays are necessary concerning the large population with refractive errors. However, varifocal optics cannot effectively address astigmatism (AST) and high-order aberration (HOAs); freeform optics has little prescription flexibility. Thus, a computational solution is desired to correct AST and HOA with high prescription flexibility and no increase in volume and hardware complexity. In addition, the computational complexity should support real-time rendering. We propose that the light field display can achieve such computational vision correction by manipulating sampling rays so that rays forming a voxel are re-focused on the retina. The ray manipulation merely requires updating the elemental image array (EIA), being a fully computational solution. The correction is first calculated based on an eye's wavefront map and then refined by a simulator performing iterative optimization with a schematic eye model. Using examples of HOA and AST, we demonstrate that corrected EIAs make sampling rays distributed within ±1 arcmin on the retina. Correspondingly, the synthesized image is recovered to nearly as clear as normal vision. We also propose a new voxel-based EIA generation method considering the computational complexity. All voxel positions and the mapping between voxels and their homogeneous pixels are acquired in advance and stored as a lookup table, bringing about an ultra-fast rendering speed of 10 ms per frame with no cost in computing hardware and rendering accuracy. Finally, experimental verification is carried out by introducing the HOA and AST with customized lenses in front of a camera. As a result, significantly recovered images are reported.

7.
Molecules ; 28(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36771035

RESUMO

Angiotensin II (Ang II), a peptide hormone generated as part of the renin-angiotensin system, has been implicated in the pathophysiology of many cardiovascular diseases such as peripheral artery disease, heart failure, hypertension, coronary artery disease and other conditions. Liraglutide, known as an incretin mimetic, is one of the glucagon-like peptide-1 (GLP-1) receptor agonists, and has been proven to be effective in the treatment of cardiovascular disorders beyond adequate glycemic control. The objective of this review is to compile our recent experimental outcomes-based studies, and provide an overview the cardiovascular protection from liraglutide against Ang II- and pressure overload-mediated deleterious effects on the heart. In particular, the mechanisms of action underlying the inhibition of oxidative stress, vascular endothelial dysfunction, hypertension, cardiac fibrosis, left ventricular hypertrophy and heart failure with liraglutide are addressed. Thus, we support the notion that liraglutide continues to be a useful add-on therapy for the management of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Hipertensão , Humanos , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Doenças Cardiovasculares/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Angiotensina II , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico
8.
Thromb J ; 20(1): 78, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36527031

RESUMO

BACKGROUND: To assess the immediate effect and factors affecting the efficacy of rotational thrombectomy (RT) in patients with thrombus-containing lower-limb ischaemic lesions. METHODS: Patients were retrospectively divided into two groups: RT and RT+ CDT (Catheter-directed thrombolysis). The RT group included patients in whom intraoperative thrombus aspiration was successful, while the RT + CDT group included patients in whom intraoperative thrombus aspiration was less effective and remedial CDT treatment was used. The primary outcome was the immediate effect of RT on thrombus-containing lower-limb ischaemic lesions. RESULTS: From May 2015 to July 2021, 170 patients (113 men, 57 women; mean age, 74.0 years) with thrombus-containing lower-limb ischaemic lesions were treated in our centre. Of these patients, 113 received RT only, while 57 received RT + CDT. There were no significant intergroup differences in terms of age, disease duration, or comorbidities, but a higher proportion of male patients and higher preoperative plasma D-dimer levels (1.23 vs. 0.84; p = .017) was observed in the RT + CDT group. There were no significant intergroup differences in terms of diagnosis, lesion characteristics, lesion location, or lesion length. Multivariate logistic regression analysis revealed that male sex (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.098-6.410; p = .030) and poor distal runoff (OR, 2.94; 95% CI, 1.439-5.988; p = .003) were associated with higher rates of additional CDT. Male patients also had a significantly longer onset time, more thrombotic occlusions, and a greater frequency of in-stent restenosis. CONCLUSIONS: RT alone or with CDT is a feasible primary treatment option for thrombus debulking. Sex significantly influences the effect of RT on thrombus-containing lower-limb ischaemic lesions.

9.
BMC Surg ; 22(1): 145, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449045

RESUMO

BACKGROUND: Aortic dissection is one of the most common emergency condition leading to internal organs or lower limb ischemia and aortic rupture. Herein, we described a reverse "cheese wire" endovascular fenestration repair (CWFER) in a patient with complicated abdominal aortic dissection which had never been reported. CASE PRESENTATION: A 62-year-old male presented abdominal tear-like pain and acute ischemia of the right lower extremity during the endovascular treatment of celiac trunk aneurysms. Computed tomography angiography (CTA) and digital subtraction angiography (DSA) showed abdominal aortic type B dissection with acute ischemia of the right lower extremity preoperatively. After a detailed preoperative examination, the patient then was performed a reverse CWFER. So far, the patient has been followed-up for 6 months, postoperative CTA demonstrated good stent-graft expansion and perfusion of bilateral common iliac arteries; also, no endoleak was detected. CONCLUSIONS: The right iliac artery in this patient supplied by false lumen, which lead to acute ischemia of the right lower extremity, needed to be treated as an emergency and dealt with promptly. CWFER is a very high-risk treatment that requires the rich experience of vascular surgeon and accurate assessment of aortic dissection. After interventional treatment, the patient recovered uneventfully after 6 months' follow-up.


Assuntos
Aneurisma da Aorta Abdominal , Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Aortografia/métodos , Prótese Vascular , Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/métodos , Humanos , Isquemia/cirurgia , Masculino , Pessoa de Meia-Idade , Stents , Resultado do Tratamento
10.
BMC Surg ; 22(1): 246, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761238

RESUMO

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a key procedure in sacral and pelvic tumor resection that provides hemorrhage control. However, few studies have been performed to capture the effects of REBOA in a nonshock condition and provide a detailed description of the changes occurring with prolonged occlusion time. This study aimed to examine the hemodynamic and metabolic effects of Zone 3 REBOA for sacral and pelvic tumor resections following different periods of REBOA. METHODS: In total, 121 patients who underwent surgical tumor resections of the pelvis and/or the sacrum with the use of aortic balloon occlusion were prospectively enrolled from October 2020 to December 2021. All cases were divided into Group A (occlusion time ≤ 60 min, n = 57) and Group B (occlusion time ≥ 90 min, n = 64). Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. RESULTS: Balloon inflation resulted in a significant increase in SBP from 106 to 120 mmHg and decreased to 96 mmHg immediately following balloon deflation. With the application of REBOA, the median blood loss was only 1200 ml (range, 400-7900). When deflating the REBOA, the arterial pH was lower than baseline (7.36 vs. 7.41, p < 0.01), the arterial lactate concentration increased from 0.9 to 1.4 mmol/L (p < 0.01), serum potassium measurements increased from 3.99 to 4.12 mmol/L, serum calcium measurements decreased from 2.31 to 2.04 mmol/L, and blood creatinine decreased from 64 to 60 µmol/L. The operating time of Group B was longer than that of patients in Group A, and the patients in Group B needed more blood units to be transfused. Although laboratory measurements, including pH, potassium, calcium, and blood creatinine, were at the same level in two groups comparison, the lactate was significantly higher in Group B after deflation (p = 0.01). CONCLUSIONS: The results of this study showed that acceptable hemodynamic and metabolic stability can be attained when the occlusion time of REBOA is more than 90 min, although the long duration of occlusion caused relatively higher lactate levels.


Assuntos
Oclusão com Balão , Procedimentos Endovasculares , Neoplasias Pélvicas , Choque Hemorrágico , Animais , Aorta , Oclusão com Balão/métodos , Cálcio , Creatinina , Modelos Animais de Doenças , Procedimentos Endovasculares/métodos , Hemodinâmica , Hemorragia/etiologia , Humanos , Lactatos , Pelve , Potássio , Sacro
11.
J Microencapsul ; 39(7-8): 654-667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36476313

RESUMO

This study aims to fabricate core-shell clarithromycin (CAM) microcapsules to cover up the bitter taste of CAM by spray drying with aqueous polymer dispersion. Water dispersion of Eudragit EPO and Surelease® were innovatively used to encapsulate CAM into microcapsules via a one-step spray-drying method. The inlet air temperature, airflow rate, CAM-polymer ratio, and particle size of CAM were optimised based on drug content and T6% (the time taken for the drug to release equal to 6% w/w). The powder properties were assessed by measuring particle size and microstructure using SEM, FT-IR, and PXRD. Furthermore, selected batch was assessed for their drug content, encapsulation efficiency, in vitro release, bitterness, and stability studies. EPO-Surelease® (1: 4) microcapsules had an average diameter (D50) of 37.69 ± 3.61 µm with a span of 2.395. The drug contents and encapsulation efficiency of EPO-Surelease®(1:4) were 10.89% and 63.7%, respectively. EPO-Surelease® (1:4) microcapsules prepared by spray drying with aqueous polymer dispersion can effectively mask the bitter taste of CAM.


Assuntos
Claritromicina , Polímeros , Espectroscopia de Infravermelho com Transformada de Fourier , Cápsulas/química , Composição de Medicamentos , Polímeros/química , Água/química
12.
J Pharmacol Exp Ther ; 377(1): 108-120, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33526603

RESUMO

Aldosterone, which regulates renal salt retention, is synthesized in adrenocortical mitochondria in response to angiotensin II. Excess aldosterone causes myocardial injury and heart failure, but potential intracardiac aldosterone synthesis has been controversial. We hypothesized that the stressed heart might produce aldosterone. We used blue native gel electrophoresis, immunoblotting, protein crosslinking, coimmunoprecipitations, and mass spectrometry to assess rat cardiac aldosterone synthesis. Chronic infusion of angiotensin II increased circulating corticosterone levels 350-fold and induced cardiac fibrosis. Angiotensin II doubled and telmisartan inhibited aldosterone synthesis by heart mitochondria and cardiac production of aldosterone synthase (P450c11AS). Heart aldosterone synthesis required P450c11AS, Tom22 (a mitochondrial translocase receptor), and the intramitochondrial form of the steroidogenic acute regulatory protein (StAR); protein crosslinking and coimmunoprecipitation studies showed that these three proteins form a 110-kDa complex. In steroidogenic cells, extramitochondrial (37-kDa) StAR promotes cholesterol movement from the outer to inner mitochondrial membrane where cholesterol side-chain cleavage enzyme (P450scc) converts cholesterol to pregnenolone, thus initiating steroidogenesis, but no function has previously been ascribed to intramitochondrial (30-kDa) StAR; our data indicate that intramitochondrial 30-kDa StAR is required for aldosterone synthesis in the heart, forming a trimolecular complex with Tom22 and P450c11AS. This is the first activity ascribed to intramitochondrial StAR, but how this promotes P450c11AS activity is unclear. The stressed heart did not express P450scc, suggesting that circulating corticosterone (rather than intracellular cholesterol) is the substrate for cardiac aldosterone synthesis. Thus, the stressed heart produced aldosterone using a previously undescribed intramitochondrial mechanism that involves P450c11AS, Tom22, and 30-kDa StAR. SIGNIFICANCE STATEMENT: Prior studies of potential cardiac aldosterone synthesis have been inconsistent. This study shows that the stressed rat heart produces aldosterone by a novel mechanism involving aldosterone synthase, Tom22, and intramitochondrial steroidogenic acute regulatory protein (StAR) apparently using circulating corticosterone as substrate. This study establishes that the stressed rat heart produces aldosterone and for the first time identifies a biological role for intramitochondrial 30-kDa StAR.


Assuntos
Aldosterona/biossíntese , Citocromo P-450 CYP11B2/metabolismo , Mitocôndrias Cardíacas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Fosfoproteínas/metabolismo , Animais , Linhagem Celular , Corticosterona/metabolismo , Masculino , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley
13.
BMC Cancer ; 21(1): 806, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256714

RESUMO

BACKGROUND: The incidence rate of adenocarcinoma of the oesophagogastric junction (AEG) has significantly increased over the past decades, with a steady increase in morbidity. The aim of this study was to explore a variety of clinical factors to judge the survival outcomes of AEG patients. METHODS: We first obtained the clinical data of AEG patients from the Surveillance, Epidemiology, and End Results Program (SEER) database. Univariate and least absolute shrinkage and selection operator (LASSO) regression models were used to build a risk score system. Patient survival was analysed using the Kaplan-Meier method and the log-rank test. The specificity and sensitivity of the risk score were determined by receiver operating characteristic (ROC) curves. Finally, the internal validation set from the SEER database and external validation sets from our center were used to validate the prognostic power of this model. RESULTS: We identified a risk score system consisting of six clinical features that can be a good predictor of AEG patient survival. Patients with high risk scores had a significantly worse prognosis than those with low risk scores (log-rank test, P-value < 0.0001). Furthermore, the areas under ROC for 3-year and 5-year survival were 0.74 and 0.75, respectively. We also found that the benefits of chemotherapy and radiotherapy were limited to stage III/IV AEG patients in the high-risk group. Using the validation sets, our novel risk score system was proven to have strong prognostic value for AEG patients. CONCLUSIONS: Our results may provide new insights into the prognostic evaluation of AEG.


Assuntos
Adenocarcinoma/mortalidade , Bases de Dados Factuais/normas , Programa de SEER/normas , Adenocarcinoma/patologia , Idoso , Junção Esofagogástrica/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
14.
Pharm Res ; 38(12): 2091-2108, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34893950

RESUMO

PURPOSE: The intention of the study was to co-delivery gemcitabine and cisplatin with totally different nature by prodrug and micelle strategy to improve its in vivo stability and antitumor effect. METHODS: A prodrug of gemcitabine (mPEG-PLG-GEM) was synthesized through the covalent conjugation between the primary amino group of gemcitabine and the carboxylic group of poly (L-glutamic acid)-g-methoxy poly (ethylene glycol) (mPEG-PLG). It was prepared into micelles by a solvent diffusion method, and then combined with cisplatin through chelation to prepare gemcitabine and cisplatin co-loaded mPEG-PLG micelles (mPEG-PLG-GEM@CDDP micelles). RESULTS: Gemcitabine and cisplatin in each micelle group were released more slowly than in solutions. In addition, pharmacokinetics behaviors of them were improved after encapsulated in prodrug micelles. T1/2z of gemcitabine and cisplatin encapsulated in micelles were prolonged to 6.357 h (mPEG-PLG-GEM), 10.490 h (mPEG-PLG@CDDP), 5.463 h and 12.540 h (mPEG-PLG-GEM@CDDP) compared with GEM@CDDP solutions (T1/2z = 1.445 h and 7.740 h). The ratio of synergy between gemcitabine and cisplatin (3:1 ~ 1:1(n/n)) was guaranteed in the systemic circulation, thus improving its antitumor effect. The results of biochemical analysis showed that GEM@CDDP-Sol was more toxic to kidneys and marrow compared with mPEG-PLG-GEM@CDDP micelles. CONCLUSIONS: By prodrug strategy, gemcitabine and cisplatin with totally different nature were prepared into micelles and obtained a better pharmacokinetic behavior. And the dual drug delivery system performed a better in vivo stability and antitumor effect compared with each single drug delivery system in the experiment. Scheme. Schematic of mPEG-PLG-GEM@CDDP micelles' formation and action process.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Portadores de Fármacos/química , Ácido Glutâmico/análogos & derivados , Polietilenoglicóis/química , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular , Cisplatino/farmacocinética , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacocinética , Composição de Medicamentos , Liberação Controlada de Fármacos , Ácido Glutâmico/química , Humanos , Masculino , Camundongos , Micelas , Pró-Fármacos/administração & dosagem , Ratos , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
15.
Cardiovasc Drugs Ther ; 35(1): 87-101, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33057968

RESUMO

PURPOSE: This study aimed to investigate whether inhibition of glucagon-like peptide-1 (GLP-1) on pressure overload induced cardiac hypertrophy and apoptosis is related to activation of ATP sensitive potassium (KATP) channels. METHODS: Male SD rats were randomly divided into five groups: sham, control (abdominal aortic constriction), GLP-1 analog liraglutide (0.3 mg/kg/twice day), KATP channel blocker glibenclamide (5 mg/kg/day), and liraglutide plus glibenclamide. RESULTS: Relative to the control on week 16, liraglutide upregulated protein and mRNA levels of KATP channel subunits Kir6.2/SUR2 and their expression in the myocardium, vascular smooth muscle, aortic endothelium, and cardiac microvasculature. Consistent with a reduction in aortic wall thickness (61.4 ± 7.6 vs. 75.0 ± 7.6 µm, p < 0.05), liraglutide enhanced maximal aortic endothelium-dependent relaxation in response to acetylcholine (71.9 ± 8.7 vs. 38.6 ± 4.8%, p < 0.05). Along with a reduction in heart to body weight ratio (2.6 ± 0.1 vs. 3.4 ± 0.4, mg/g, p < 0.05) by liraglutide, hypertrophied cardiomyocytes (371.0 ± 34.4 vs. 933.6 ± 156.6 µm2, p < 0.05) and apoptotic cells (17.5 ± 8.2 vs. 44.7 ± 7.9%, p < 0.05) were reduced. Expression of anti-apoptotic protein BCL-2 and contents of myocardial ATP were augmented, and expression of cleaved-caspase 3 and levels of serum Tn-I/-T were reduced. Echocardiography and hemodynamic measurement showed that cardiac systolic function was enhanced as evidenced by increased ejection fraction (88.4 ± 4.8 vs. 73.8 ± 5.1%, p < 0.05) and left ventricular systolic pressure (105.2 ± 10.8 vs. 82.7 ± 7.9 mmHg, p < 0.05), and diastolic function was preserved as shown by a reduction of ventricular end-diastolic pressure (-3.1 ± 2.9 vs. 6.7 ± 2.8 mmHg, p < 0.05). Furthermore, left ventricular internal diameter at end-diastole (5.8 ± 0.5 vs. 7.7 ± 0.6 mm, p < 0.05) and left ventricular internal diameter at end-systole (3.0 ± 0.6 vs. 4.7 ± 0.4 mm, p < 0.05) were improved. Dietary administration of glibenclamide alone did not alter all the parameters measured but significantly blocked liraglutide-exerted cardioprotection. CONCLUSION: Liraglutide ameliorates cardiac hypertrophy and apoptosis, potentially via activating KATP channel-mediated signaling pathway. These data suggest that liraglutide might be considered as an adjuvant therapy to treat patients with heart failure.


Assuntos
Apoptose/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Glibureto/farmacologia , Canais KATP/efeitos dos fármacos , Liraglutida/farmacologia , Animais , Cardiomegalia , Quimioterapia Combinada , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
16.
World J Surg Oncol ; 19(1): 140, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952258

RESUMO

BACKGROUND: Treatments for metastatic fracture of the humeral shaft continue to evolve as advances are made in both oncological and operative management. The purposes of this study were to critically evaluate the effectiveness of intercalary endoprostheses in treating metastatic humeral shaft fractures and to clarify the surgical indications for this technique. METHODS: Sixty-three patients treated surgically for 66 metastatic fractures of the humerus shaft were retrospectively reviewed. Intramedullary nailing (IMN) was performed in 16 lesions, plate fixation (PF) in 33 lesions, and prosthetic replacement in 17 lesions. The operative time, intraoperative blood loss, and postoperative complications were noted. The function of the upper extremities was assessed by the Musculoskeletal Tumor Society (MSTS) score and American Shoulder and Elbow Surgeons (ASES) score. All included patients were followed until reconstructive failure or death. RESULTS: The operative time was relatively shorter in the prosthesis group than in either the IMN group (p = 0.169) or PF group (p = 0.002). Notably, intraoperative blood loss was significantly less in the prosthesis group than in either the IMN group (p = 0.03) or PF group (p = 0.012). The average follow-up time was 20.3 (range, 3-75) months, and the overall survival rate was 59.7% at 12 months and 46.7% at 24 months. One rotator cuff injury, 3 cases of iatrogenic radial nerve palsy, 5 cases of local tumor progression, and 1 mechanical failure occurred in the osteosynthesis group, whereas one case of aseptic loosening of the distal stem and one case of local relapse were observed in the prosthesis group. There were no significant differences in functional scores among the three groups. CONCLUSIONS: Intercalary prosthetic replacement of the humeral shaft may be a reliable solution for pathologic fractures patients; it is indicated for lesions with substantial bone loss, or accompanied soft tissue mass, or for those patients with better prognosis.


Assuntos
Fixação Intramedular de Fraturas , Fraturas do Úmero , Neoplasias , Placas Ósseas , Humanos , Fraturas do Úmero/cirurgia , Úmero/cirurgia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
17.
BMC Musculoskelet Disord ; 22(1): 549, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134687

RESUMO

BACKGROUND AND OBJECTIVES: Treatment of benign osteolytic lesions in the femoral head and neck can be extremely challenging, particularly in children with open physis or for aggressive tumors with pathological fracture. There remains the difficult management decision as to whether to perform complete excision of the involved area or only curettage. Moreover, there is no agreed consensus on the optimal approach to lesion access when performing curettage, which included the transcervical, open and direct approach. The current systematic review aims to provide guidance for selection of surgical methods in clinical practice by comparing the advantages and drawbacks of different procedures. METHODS: A comprehensive literature search of PubMed, Embase and Web of Science databases were executed for human studies restricted to the English language. The search was filtered to include studies published from January 1980 to January 2020. RESULTS: A total of 33 articles including 274 patients were enrolled in the final analysis. The most common diagnosis was chondroblastoma (CBT) (104, 38.0%), followed by giant cell tumor (GCT) (56, 20.4%). There were 57 (20.8%) patients with pathological fracture. Intralesional curettage was performed in 257 (93.8%) patients with the local recurrence of 12.5% at the mean follow-up of 51.5 months. The patients who were presented with open physis or curetted via transcervical approach developed higher local recurrence in patients with CBT (P < 0.001). The local recurrence rate of GCT is 33.3% after curettage, while 8 of 9 (88.9%) patients with fracture were treated successfully with joint preservation. Two of 45 (4.4%) patients developed avascular necrosis (AVN) of femoral head after surgical hip dislocation. The reported Musculoskeletal Tumor Society (MSTS) Score was comparable among patients with different approaches to curettage. CONCLUSION: The majority of benign osteolytic lesions in the femoral head and neck can be treated with intralesional curettage with acceptable local tumor control and satisfactory function. The incidence of local recurrence might be decreased dramatically for lesion access under direct visualization. The native joint maintenance could be achieved even in patients with aggressive lesions presenting pathological fracture.


Assuntos
Neoplasias Ósseas , Cabeça do Fêmur , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Criança , Curetagem , Fêmur , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Resultado do Tratamento
18.
Biodegradation ; 32(1): 53-71, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33428058

RESUMO

In this study, a distinct inoculum was investigated as an isolated variable within sequencing batch reactors via a comparison of the 4-fluoroaniline (4-FA) or 2,4-difluoroaniline (2,4-DFA) removal amounts. The inocula were derived from a treatment plant for treating pharmaceutical wastewater plus a small amount of municipal sewage (PMS), a treatment plant for treating fluoridated hydrocarbon wastewater (FHS), and a treatment plant for treating the comprehensive wastewater in an industrial park (CIS). There were slight differences among the degradation patterns of the 4-FA for the three inocula, whether during the enrichment period or the high concentration shock period. In contrast, it was observed that the degradation efficiency of 2,4-DFA initially varied with the inocula. The FHS-derived inoculum was determined to be optimal, exhibiting the earliest degradation reaction only after an acclimation of 7 days had the highest degradation rate constant of 0.519 h-1, and had the fastest recovery time of three weeks after high concentration shock. Additionally, compared with the PMS-derived inoculum, the CIS-derived inoculum exhibited an earlier degradation reaction within three weeks, and a higher microbial diversity, but a lower shock resistance and degradation rate constant of 0.257 h-1. High-throughput sequencing demonstrated that each final consortium was different in composition, and the microbial consortia developed well on the inoculum and substrate. In comparison of the similarity among the three 2,4-DFA enrichment cultures, the higher similarity (63.9-70.0%) among three final consortia enriching with 4-FA was observed. The results indicated that the inoculum played an important role in the degradation of FAs and the microbial bacterial communities of final consortia, and the effect extent might well depend on the fluorinated level of FAs.


Assuntos
Reatores Biológicos , Microbiota , Compostos de Anilina , Biodegradação Ambiental , Esgotos
19.
Eur J Vasc Endovasc Surg ; 60(6): 854-861, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183920

RESUMO

OBJECTIVE: The left subclavian artery (LSA) origin can be intentionally covered by stent grafts, to provide adequate proximal landing zones during thoracic endovascular repair for Stanford type B aortic dissections (TBADs). To preserve the LSA, a novel single branched stent graft, named "Castor" was designed and a clinical trial conducted to investigate its suitability. METHODS: From April 2013 to March 2015, 73 patients with TBAD were treated by Castor stent grafts at 11 Chinese tertiary hospitals as part of a single arm prospective clinical trial. There were 50 acute (<2 weeks [68.5%]) and 23 chronic aortic dissections (>2 weeks [31.5%]). RESULTS: The technical success rate was 97% (n = 71/73). The two failures were caused by occlusion of the branch section of the stent graft. There were four intra-operative endoleaks (two type Ia, two type B from the LSA). The endoleak rate was 5% (n = 4/73). There was one in hospital death and no major complications. The median follow up time was 61 months (range 48-72 months). The mortality was 5% (n = 4/73) within one year and 7% within six years (n = 5/73). Two deaths were of unknown cause and three were not related to the aorta. Two new entry tears were found on the proximal or distal edge of the stent graft and were retreated endovascularly. Six occlusions of the branch section of the Castor stent graft were found, and the follow up patency rate of the branch section was 93% (n = 63/68). Two intra-operative endoleaks were left during follow up and eventually disappeared according to the latest computed tomography angiograms. CONCLUSION: For patients with TBADs needing anchoring proximal to the origin of LSA, the Castor single branched stent graft may provide an easily manipulated, safe, and effective endovascular treatment.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Procedimentos Endovasculares/métodos , Artéria Subclávia/cirurgia , Enxerto Vascular/métodos , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Prótese Vascular/efeitos adversos , Doença Crônica , Endoleak/etiologia , Procedimentos Endovasculares/instrumentação , Feminino , Seguimentos , Humanos , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , Recidiva , Stents Metálicos Autoexpansíveis/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento , Enxerto Vascular/instrumentação , Grau de Desobstrução Vascular , Adulto Jovem
20.
Mol Biol Rep ; 47(2): 1207-1222, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31820314

RESUMO

Aldosterone produced in adrenal glands by angiotensin II (Ang II) is known to elicit myocardial fibrosis and hypertrophy. This study was designed to test the hypothesis that Ang II causes cardiac morphological changes through the steroidogenic acute regulatory protein (StAR)/aldosterone synthase (AS)-dependent aldosterone synthesis primarily initiated in the heart. Sprague-Dawley rats were randomized to following groups: Ang II infusion for a 4-week period, treatment with telmisartan, spironolactone or adrenalectomy during Ang II infusion. Sham-operated rats served as control. Relative to Sham rats, Ang II infusion significantly increased the protein levels of AT1 receptor, StAR, AS and their tissue expression in the adrenal glands and heart. In coincidence with reduced aldosterone level in the heart, telmisartan, an AT1 receptor blocker, significantly down-regulated the protein level and expression of StAR and AS. Ang II induced changes in the expression of AT1/StAR/AS were not altered by an aldosterone receptor antagonist spironolactone. Furthermore, Ang II augmented migration of macrophages, protein level of TGFß1, phosphorylation of Smad2/3 and proliferation of myofibroblasts, accompanied by enhanced perivascular/interstitial collagen deposition and cardiomyocyte hypertrophy, which all were significantly abrogated by telmisartan or spironolactone. However, adrenalectomy did not fully suppress Ang II-induced cell migration/proliferation and fibrosis/hypertrophy, indicating a role of aldosterone synthesized within the heart in pathogenesis of Ang II induced injury. These results indicate that myocardial fibrosis and hypertrophy stimulated by Ang II is associated with tissue-specific activation of aldosterone synthesis, primarily mediated by AT1/StAR/AS signaling pathways.


Assuntos
Angiotensina II/metabolismo , Cardiomegalia/etiologia , Cardiomegalia/metabolismo , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Citocromo P-450 CYP11B2/metabolismo , Fosfoproteínas/genética , Glândulas Suprarrenais/metabolismo , Animais , Biomarcadores , Biópsia , Cardiomegalia/patologia , Cardiomiopatias/patologia , Colágeno/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Fibrose , Imuno-Histoquímica , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Modelos Biológicos , Miocárdio/metabolismo , Miocárdio/patologia , Miofibroblastos/metabolismo , Ratos , Receptor Tipo 1 de Angiotensina/metabolismo , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo
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