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1.
Int J Surg ; 110(4): 2044-2054, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38215263

RESUMO

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease among patients with obesity. Bariatric surgery, such as sleeve gastrectomy (SG), shows promise in improving the unfavorable condition of MAFLD. Transient elastography (TE) can be utilized to assess the extent of steatosis and liver fibrosis, providing a noninvasive method for preoperative prediction and postoperative evaluation of MAFLD. This study aims to investigate the effectiveness of TE in diagnosing MAFLD by evaluating liver steatosis and tissue stiffness, as well as assessing the early impact of SG in the treatment of obesity-associated MAFLD. METHODS: In this study, the authors collected preoperative and 6-month postoperative data from patients with obesity who were diagnosed with MAFLD by intraoperative liver biopsy. The patients underwent SG at our hospital between August 2021 and April 2023. The authors estimated the diagnostic accuracy for the steatosis and fibrosis categories using the area under the receiver operating characteristic curve (AUROC). The authors also evaluated the influence of disease prevalence on the positive predictive value and negative predictive value. MAFLD diagnosis was based on the liver steatosis activity and fibrosis scoring system. The authors used univariate and multivariate logistic regression analyses to identify factors contributing to severe MAFLD. To visualize the results, the authors created a nomogram and enhanced it with bootstrap resampling for internal validation. Additionally, the authors plotted receiver operating characteristic and calibration curves. The authors compared preoperative and postoperative data, including general information, laboratory tests, and TE results, to assess the early impact of SG in the treatment of obesity-associated MAFLD. RESULTS: Based on the results of liver biopsy, the AUROC for controlled attenuation parameter (CAP) in identifying steatosis was found to be 0.843 (95% CI: 0.729-0.957) for S≥S1, 0.863 (95% CI: 0.786-0.940) for S≥S2, and 0.872 (95% CI: 0.810-0.934) for S=S3. The Youden limits for S≥S1, S≥S2, and S≥S3 were determined to be 271 dB/m, 292 dB/m, and 301 dB/m, respectively. Similarly, the AUROC for liver stiffness measurement (LSM)/E in detecting liver fibrosis was 0.927 (95% CI: 0.869-0.984) for F≥F2, 0.919 (95% CI: 0.824-0.979) for F≥F3, and 0.949 (95% CI: 0.861-0.982) for F=F4, with Youden cutoff values of 7.5 kPa, 8.3 kPa, and 10.4 kPa, respectively. Patients with A≥3 and/or F≥3 were classified as having severe MAFLD. Multivariate logistic regression analysis identified CAP, E, LDL, and AST as the best diagnostic factors for severe MAFLD, and a nomogram was constructed based on these factors. The AUROC of the nomogram for the assessment of severe MAFLD was 0.824 (95% CI: 0.761-0.887), which was further validated by 1000 bootstrap resamplings with a bootstrap model area under curve of 0.823. Finally, after a 6-month follow-up period, the steatosis grade and fibrosis stage of the patients were graded based on the optimal cutoff values for CAP and LSM. Significant reductions in BMI, waist circumference, HbA1c, fasting glycemia, triglycerides, high density lipoprotein (HDL), glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), gamma glutamyl transpeptidase (GGT), CAP, LSM, steatosis grade, and fibrosis stage were observed compared to the preoperative values. CONCLUSION: In this prospective study, the authors investigated the use of CAP and LSM as alternatives to liver biopsy for evaluating hepatic steatosis and fibrosis in patients with obesity combined with MAFLD. Furthermore, the authors examined the impact of SG on metabolic indicators and the progression of fatty liver disease during the early postoperative period, and observed significant improvements in both aspects.


Assuntos
Técnicas de Imagem por Elasticidade , Gastrectomia , Humanos , Técnicas de Imagem por Elasticidade/métodos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , China/epidemiologia , Estudos Retrospectivos , Cirurgia Bariátrica , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Fígado Gorduroso/diagnóstico por imagem , Curva ROC , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/cirurgia , Obesidade/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , População do Leste Asiático
2.
Curr Cancer Drug Targets ; 24(3): 368-374, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37533242

RESUMO

BACKGROUND: A 43-year-old female patient was found to have an abnormal liver function, abnormally elevated alpha-fetoprotein and space-occupying lesions in the liver on routine screening. The patient came to our hospital for further diagnosis and treatment. CASE PRESENTATION: Investigations: Laboratory investigations, digital subtraction angiography (DSA) of the hepatic artery, abdominal ultrasound examination, and magnetic resonance imaging (MRI) scan were conducted using pathological staining and immunohistochemistry. DIAGNOSIS: Clinical diagnosis: cT3NxM0. Barcelona clinic liver cancer (BCLC) staging: BCLC stage C. China liver cancer (CNLC) staging: CNLC IIIa. DISCUSSION: The patient was hospitalized for the first time for transcatheter arterial chemoembolization (TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (HAIC). Then, the second and third hospital admissions were given HAIC based on FOLFOX. Camrelizumab and oncolytic virus were also injected into the liver cancer through the microcatheter in the first three treatments. On the fourth admission, the patient's indicators were improved, and the tumor shrank. Furthermore, as the patient suffered adverse reactions the first few times, we suspended the treatment of FOLFOX and the oncolytic virus. Before surgical treatment, lenvatinib was used throughout the treatment. On the fifth admission, the patient underwent liver cancer resection. CONCLUSION: It proves the value of multiple combination therapy, which can provide guidance for patients with advanced hepatocellular carcinoma that cannot be surgically removed.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Feminino , Humanos , Adulto , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Quimioembolização Terapêutica/métodos , Resultado do Tratamento , Infusões Intra-Arteriais
3.
Obes Facts ; 16(5): 484-496, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37598680

RESUMO

INTRODUCTION: Bariatric surgery has grown in popularity over the past two decades, especially in the Asia-Pacific. Correspondingly, researchers' interest in this field has also increased. This study aims to perform a bibliometric analysis of publications from Asia-Pacific represented by the International Federation for the Surgery of Obesity and Metabolic Disorders Asia-Pacific Chapter (IFSO-APC) and investigate the relevant factors that might affect the publications. METHODS: The search terms for bariatric surgery were searched in Web of Science focusing on the period 2000-2021. Bibliometric analysis was performed after screening the search results. Univariate and multivariate regression analyses were performed on the number of publications and corresponding indicators obtained from official agencies. RESULTS: A total of 9,547 publications in IFSO-APC were retrieved, of which China had the largest number with 2,782 publications. Authors and journals with major contributions were listed. The authors' or affiliations' cooperation networks mainly were limited to domestic. "Bariatric surgery" was the most frequent keyword with 2,063 times and also the largest cluster. "Morbid obesity" was the strongest citation bursts. Multivariate analysis found that the number of publications in each country/region was associated with body mass index ≥25 kg/m2, gross domestic product, and total population. CONCLUSION: Generally, Asia-Pacific represented by IFSO-APC scientific publications on bariatric surgery has grown significantly in the last two decades, but cooperation between countries/regions should be strengthened. "Morbid obesity" is the focus and frontier of research in this field.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Humanos , Ásia/epidemiologia , Bibliometria , Cirurgia Bariátrica/métodos , China/epidemiologia , Obesidade Mórbida/cirurgia
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 300: 122908, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37247553

RESUMO

Real-time and in-situ fluorescence visualization technologies have attention to in the forensic analysis of latent fingerprints (LFPs). The fingerprint powders with high performance and biocompatibility are essential for imaging LFPs with high definition and safety. In this work, five quaternary protoberberine alkaloid (QPA) derivatives were analyzed with reorganization energy and four-point calculations to explain the relationship between the substituent effect and luminescent properties and further resolve the luminous behaviors of four QPA-based natural products in solution. Thanks to the restriction of the intramolecular motions mechanism, aggregation-induced emission (AIE) active BBC nanoaggregates could sensitively detect explosive analog, 2,4,6-trinitrophenol, at a nanomolar level (9.8 nM of detection limit). Combined with natural montmorillonite (MMT) mineral powders, three levels of details for fingerprints were successfully imaged with solid-luminous BBC/MMT nanocomposites. The insight into the substituted effect of alkoxy groups on the QPA framework not only provides a new concept to design rotor-free AIE luminogens but also expands natural products and their nanocomposites into LFP and detection applications.


Assuntos
Antineoplásicos , Alcaloides de Berberina , Pós , Bentonita , Fluorescência
5.
ACS Sustain Chem Eng ; 11(18): 7062-7071, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37192891

RESUMO

Improved sustainability is associated with elastomers that readily breakdown in the environment at end of life and, as importantly, that can be reprocessed/reused long before end of life arises. We report the preparation of silicone elastomers that possess both thermoplasticity-reprocessability-and antioxidant activity. A combination of ionic and H-bonding links natural phenolic antioxidants, including catechol, pyrogallol, tannic acid, and others, to telechelic aminoalkylsilicones. The mechanical properties of the elastomers, including their processability, are intimately linked to the ratio of [ArOH]/[H2NR] that was found to be optimal when the ratio exceeded 1:1.

6.
Eur Phys J E Soft Matter ; 46(5): 33, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37171676

RESUMO

When polydimethylsiloxane elastomers are produced, in the absence of great care, chains remain that are unbound to the cross-linked matrix. Due to the unbound chains swelling the crosslinked matrix, these materials are gels. We have developed a simple process to prepare well-controlled elastomeric thin films which do not rely on unknown commercial formulations.

7.
Diabetes Metab J ; 47(4): 559-570, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37096418

RESUMO

BACKGRUOUND: MicroRNAs (miRNAs) exert an essential contribution to obesity and type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences of miRNAs in the presence and absence of T2DM in patients with obesity, as well as before and after bariatric surgery in T2DM patients with obesity. Characterization of the common changes in both was further analyzed. METHODS: We enrolled 15 patients with obesity but without T2DM and 15 patients with both obesity and T2DM. Their preoperative clinical data and serum samples were collected, as well as 1 month after bariatric surgery. The serum samples were analyzed by miRNA sequencing, and the miRNAs profiles and target genes characteristics were compared. RESULTS: Patients with T2DM had 16 up-regulated and 32 down-regulated miRNAs compared to patients without T2DM. Improvement in metabolic metrics after bariatric surgery of T2DM patients with obesity was correlated with changes in miRNAs, as evidenced by the upregulation of 20 miRNAs and the downregulation of 30 miRNAs. Analysis of the two miRNAs profiles identified seven intersecting miRNAs that showed opposite changes. The target genes of these seven miRNAs were substantially enriched in terms or pathways associated with T2DM. CONCLUSION: We determined the expression profiles of miRNAs in the obese population, with and without diabetes, before and after bariatric surgery. The miRNAs that intersected in the two comparisons were discovered. Both the miRNAs discovered and their target genes were closely associated with T2DM, demonstrating that they might be potential targets for the regulation of T2DM.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , MicroRNAs , Humanos , MicroRNAs/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Obesidade/complicações , Obesidade/genética , Regulação para Baixo
8.
J Oncol ; 2023: 2733232, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36968641

RESUMO

Colorectal cancer (CRC) is a common and highly lethal gastrointestinal malignancy. Immunotherapy has shown positive efficacy in the treatment of CRC; however, only a minority of patients benefit from immunotherapy. The aim of this study is to construct a cuproptosis-related lncRNA (CRLs) risk score model to predict the prognosis and immune infiltration of CRC patients. Firstly, we synthetically analyzed 19 cuproptosis-related genes (CRGs) from CRC samples derived from the TCGA and obtained 33 CRLs that were significantly associated with prognosis. Next, we defined three cuproptosis modification patterns via consensus clustering analysis (C1, C2, and C3). Further analysis showed that there were significant differences in the abundance of B cells, NK cells, fibroblasts, monocytes, CD8+ cells, bone marrow dendritic cells, and cytotoxic lymphocytes in different clusters. In addition, the LASSO regression screened out 6 individual CRLs (AC009315.1, PLS3-AS1, ZEB1-AS1, AC007608.3, AC010789.2, and AC010207.1) closely related to the prognosis of CRC. We found that the low-risk group had better survival prognoses in patients. Furthermore, the high-risk group had lower immune scores and exhibited lower CD8+ T cell infiltration. Moreover, the low-risk group had lower immune exclusion, immune dysfunction and TIDE scores than the high-risk group. Interestingly, the lncRNAs in our risk model were positively associated with most immune checkpoints. CD274 (PD-L1), CTLA4, and HAVCR2 (TIM3) were positively correlated with risk scores. Moreover, MSI-H patients had lower risk scores than MSI-L patients, and IPS scores were significantly higher in the low CRLs score group. In conclusion, we constructed a novel risk score model with6 lncRNAs related to cuproptosis, which may be a potential biomarker for evaluating the prognosis and immune treatment for CRC.

9.
Int J Surg ; 109(4): 850-860, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36974733

RESUMO

BACKGROUND: The purpose of this research was to determine the index that contributes the most to assessing the effectiveness of weight loss 1 year following bariatric surgery and to implement it as the clinical outcome to develop and confirm a nomogram to predict whether bariatric surgery would be effective. METHODS: Patient information was extracted from the Chinese Obesity and Metabolic Surgery Database for this retrospective study. The most contributing weight loss effectiveness evaluation index was created using canonical correlation analysis (CCA), and the predictors were screened using logistic regression analysis. A nomogram for estimating the likelihood of effectiveness of weight loss was constructed, and its performance was further verified. RESULTS: Information was obtained for 540 patients, including 30 variables. According to the CCA, ≥25 percentage total weight loss was found to be the most correlated with patient information and contribute the most as a weight loss effectiveness evaluation index. Logistic regression analysis and nomogram scores identified age, surgical strategy, abdominal circumference, weight loss history, and hyperlipidemia as predictors of effectiveness in weight loss. The prediction model's discrimination, accuracy, and clinical benefit were demonstrated by the consistency index, calibration curve, and decision curve analysis. CONCLUSIONS: The authors determined a 25 percentage total weight loss as an index for weight loss effectiveness assessment by CCA and next established and validated a nomogram, which demonstrated promising performance in predicting the probability of effectiveness of weight loss in bariatric surgery. The nomogram might be a valuable tool in clinical practice.


Assuntos
Cirurgia Bariátrica , Nomogramas , Humanos , Estudos Retrospectivos , Obesidade , Probabilidade
10.
Microsc Res Tech ; 86(2): 232-241, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36412215

RESUMO

The occurrence and development of blood vessels play a key role in different stages of tumor growth, while current imaging techniques are difficult to detect early tumor angiogenesis because of their low sensitivity. Therefore, this article introduces high-sensitivity optical imaging technology to achieve early tumor diagnosis by detecting tumor angiogenesis. Liver and pancreatic tumor models in nude mice were respectively established to represent tumors with a rich or poor blood supply. The two optical imaging methods, in vivo confocal fluorescence imaging and photoacoustic imaging, were used to detect tumor angiogenesis at different stages. Finally, the changes in blood vessels were verified by immunostaining. Both autoluminescence imaging and pathological staining confirmed that these two tumor models were successfully established. In vivo confocal fluorescence imaging found that the early tumor blood vessel structure had obvious characteristics: disorder, tortuous deformation, thin diameter, which were significantly different from the normal tissues. Photoacoustic imaging could effectively identify blood vessels inside early tumors, which were small and disordered and might be used as one of the predictors of early tumor development. CD31 immunostaining was used to evaluate the vascular status of tumors at different stages and under different blood supply conditions. The vascular structures observed under the microscope in the two tumor models were consistent with the results observed by optical imaging methods. The optical imaging methods could monitor the characteristics of angiogenesis in the rich or poor blood supply tumors, especially the early diagnosis of tumors.


Assuntos
Neovascularização Patológica , Neoplasias Pancreáticas , Camundongos , Animais , Camundongos Nus , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Imagem Óptica/métodos , Diagnóstico Precoce
11.
Anticancer Drugs ; 34(1): e1-e8, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36066392

RESUMO

The lung is the most common metastatic organ of primary liver cancer, accounting for 39.5-53.8% of extrahepatic metastasis, which seriously affects the prognosis of patients. In clinical treatment, it is difficult for one therapeutic schedule to achieve the desired effect sometimes, requiring two or even several combined methods for liver cancer lung metastasis. In this study, we report a liver cancer patient with lung metastases who received various combined therapies. However, the comprehensive treatment did not improve the patient's pulmonary metastasis symptoms until after the application of immunotherapy, and the lung metastases were gradually cured.


Assuntos
Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Hepatectomia , Prognóstico , Imunoterapia
12.
Obes Rev ; 24(1): e13522, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36336901

RESUMO

Atrial natriuretic peptide (ANP) has been considered to exert an essential role as a cardiac secretory hormone in the regulation of hemodynamic homeostasis. As the research progresses, the role of ANP in the crosstalk between heart and lipid metabolism has become an interesting topic that is attracting the interest of researchers. The regulation of ANP in lipid metabolism shows favorable effects, particularly the activation of brown adipose tissue (BAT). The complex regulatory network of ANP on BAT has not been fully outlined. This narrative review critically evaluated the existing literature on the regulatory effects of ANP on BAT. In general, we have summarized the expression of ANP and its receptors in various human tissues, analyzed the progress of research on the relationship between the ANP and BAT, and described several potential pathways of ANP to BAT. Exogenous ANP, natriuretic peptide receptor C (NPRC) deficiency, cold exposure, bariatric surgery, and cardiac or renal insufficiency could all contribute to BAT expression by increasing circulating ANP levels.


Assuntos
Fator Natriurético Atrial , Receptores do Fator Natriurético Atrial , Humanos , Fator Natriurético Atrial/metabolismo , Fator Natriurético Atrial/farmacologia , Receptores do Fator Natriurético Atrial/genética , Receptores do Fator Natriurético Atrial/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo/metabolismo
13.
Polymers (Basel) ; 14(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36433164

RESUMO

Vitamin C is widely used as an antioxidant in biological systems. The very high density of functional groups makes it challenging to selectively tether this molecule to other moieties. We report that, following protection of the enediol as benzyl ethers, the introduction of an acrylate ester at C1 is straightforward. Ascorbic acid-modified silicones were synthesized via aza-Michael reactions of aminoalkylsilicones with ascorbic acrylate. Viscous oils formed when the amine/acrylate ratios were <1. However, at higher amine/acrylate ratios with pendent silicones, a double reaction occurred to give robust elastomers whose modulus is readily tuned simply by controlling the ascorbic acid amine ratio that leads to crosslinks. Reduction with H2/Pd removed the benzyl ethers and led to increased crosslinking, and either liberated the antioxidant small molecule or produced antioxidant elastomers. These pro-antioxidant elastomers show the power of exploiting natural materials as co-constituents of silicone polymers.

14.
ACS Nano ; 16(7): 10840-10851, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35816171

RESUMO

Colloidal quantum wells (CQWs) have emerged as a promising family of two-dimensional (2D) optoelectronic materials with outstanding properties, including ultranarrow luminescence emission, nearly unity quantum yield, and large extinction coefficient. However, the performance of CQWs-based light-emitting diodes (CQW-LEDs) is far from satisfactory, particularly for deep red emissions (≥660 nm). Herein, high efficiency, ultra-low-efficiency roll-off, high luminance, and extremely saturated deep red CQW-LEDs are reported. A key feature for the high performance is the understanding of charge dynamics achieved by introducing an efficient electron transport layer, ZnMgO, which enables balanced charge injection, reduced nonradiative channels, and smooth films. The CQW-LEDs based on (CdSe/CdS)@(CdS/CdZnS) ((core/crown)@(colloidal atomic layer deposition shell/hot injection shell)) show an external quantum efficiency of 9.89%, which is a record value for 2D nanocrystal LEDs with deep red emissions. The device also exhibits an ultra-low-efficiency roll-off and a high luminance of 3853 cd m-2. Additionally, an exceptional color purity with the CIE coordinates of (0.719, 0.278) is obtained, indicating that the color gamut covers 102% of the International Telecommunication Union Recommendation BT 2020 (Rec. 2020) standard in the CIE 1931 color space, which is the best for CQW-LEDs. Furthermore, an active-matrix CQW-LED pixel circuit is demonstrated. The findings imply that the understanding of charge dynamics not only enables high-performance CQW-LEDs and can be further applied to other kinds of nanocrystal LEDs but also is beneficial to the development of CQW-LEDs-based display technology and related integrated optoelectronics.

15.
Front Chem ; 10: 887900, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35494648

RESUMO

Organic light-emitting diodes (OLEDs) have great potential for display, lighting, and near-infrared (NIR) applications due to their outstanding advantages such as high efficiency, low power consumption, and flexibility. Recently, it has been found that the ultrathin emitting nanolayer technology plays a key role in OLEDs with simplified structures through the undoped fabricated process, and exciplex-forming hosts can enhance the efficiency and stability of OLEDs. However, the elementary structure and mechanism of the energy transfer process of ultrathin emitting nanolayers within interface exciplexes are still unclear. Therefore, it is imminently needed to explore the origin of ultrathin emitting nanolayers and their energy process within exciplexes. Herein, the mechanism of films growing to set ultrathin emitting nanolayers (<1 nm) and their energy transfer process within interface exciplexes are reviewed and researched. The UEML phosphorescence dye plays a key role in determining the lifetime of excitons between exciplex and non-exciplex interfaces. The exciplex between TCTA and Bphen has longer lifetime decay than the non-exciplex between TCTA and TAPC, facilitating exciton harvesting. The findings will be beneficial not only to the further development of OLEDs but also to other related organic optoelectronic technologies.

16.
Cancer Lett ; 523: 1-9, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34530049

RESUMO

Pancreatic cancer is one of the common malignant tumors of the digestive system, and its clinical treatment is still very challenging. Most of the pancreatic cancer chemotherapeutic drugs have poor plasma stability, low cell uptake efficiency, and are prone to developing drug resistance and toxic side effects. Besides, pancreatic cancer often has a dense extracellular matrix, which consists of collagens, hyaluronic acid, and other proteoglycans. Among them, hyaluronic acid is a key component of the dense matrix, which results in vascular compression and insufficient perfusion, and hinders the delivery of chemotherapeutic drugs. In this study, we explore using hyaluronidase in tumor-bearing mice to eliminate the hyaluronic acid barrier, to reduce blood vessel compression and reshape the tumor microenvironment. In addition, we evaluate using doxorubicin-loaded nanoprobes to improve the stability and local tumor-killing effect of the drug. The nanoprobes have the characteristics of near-infrared optical imaging, which are used to monitor the tumor size in real-time during the treatment process, and dynamically observe the tumor inhibitory effect. The results show that elimination of the hyaluronic acid barrier combined with the doxorubicin-loaded nanoprobes can greatly increase drug penetration into tumor tissue and improve the effectiveness of chemotherapy drugs. This study provides a novel strategy for the treatment of pancreatic cancer.


Assuntos
Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Ácido Hialurônico/farmacocinética , Hialuronoglucosaminidase/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Pressão Sanguínea/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanotubos de Carbono , Neoplasias Pancreáticas/diagnóstico por imagem , Fluxo Sanguíneo Regional/efeitos dos fármacos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Microambiente Tumoral/efeitos dos fármacos
17.
Front Med (Lausanne) ; 7: 351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850882

RESUMO

The 78-kDa glucose-regulated protein (GRP78) plays an important part in maintaining protein stability, regulating protein folding, and inducing apoptosis autophagy, which is considered as a powerful protein. Meanwhile, it also plays a role in ensuring the normal function of organs. In recent years, more and more researches have been carried out on the targeted therapy of GRP78, mainly focusing on its relevant role in tumor and its role as a major modulator and modulator of subordinate pathways. The ability of GRP78 to respond to endoplasmic reticulum stress (ERS) determines whether tumor cells survive and whether the changes in expression level of GRP78 regulated by endoplasmic reticulum (ER) caused by various factors will directly or indirectly affect cell proliferation, apoptosis, and injury, or reduce the body's defense ability, or have protective effects on various organs.

18.
ACS Appl Mater Interfaces ; 11(16): 14526-14537, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30776888

RESUMO

Continuously updated diagnostic methods and advanced imaging methods have led to an increase in the early detection rate of small liver cancer; however, even with current diagnosis methods, it is still challenging to accurately judge a nodule with a diameter less than 2 cm whether it is hepatocellular carcinoma or liver cirrhosis. To solve this issue, a new technology is needed to distinguish above two kinds of liver nodules. There is an emerging imaging method that improves tissue resolution and sensitivity to detect micronodules with diameters less than 2 cm. To detect micronodules, photoacoustic imaging was used to provide noninvasive images at depths of several centimeters with a resolution of approximately 100 µm. To improve specificity, we developed a probe that specifically targets hepatocellular carcinoma by recognizing the biomarker GPC3 on the hepatocellular carcinoma cell membrane. The probe not only has a strong photoacoustic signal but also has a magnetic resonance signal. Furthermore, the material owns photothermal effect that absorbs longer wavelength light and releases heat that effectively and accurately kills tumor cells, thus improving patient's survival and postoperative quality of life. Herein, we present a new technology that uses photoacoustic imaging to image and target microhepatocellular carcinoma biological processes derived from liver cirrhosis with high spatial resolution.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/química , Animais , Carcinoma Hepatocelular/metabolismo , Meios de Contraste/química , Meios de Contraste/farmacologia , Feminino , Células Hep G2 , Humanos , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C
19.
Biomaterials ; 195: 13-22, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30599289

RESUMO

Pancreatic cancer is one of the most lethal malignancies worldwide. The existing therapeutic regimen in the clinic for advanced inoperable carcinomas are far from satisfactory, thus it is urgent to seek more effective anticancer strategies. In the pursuit of novel, more effective interventions, photothermal therapy (PTT) based on nanomaterials has attracted increased attention. Recent advances in related fields have catalyzed the generation of novel nanoprobes, such as organic dyes, metal nanoparticles. However, organic dyes are poorly stable and easy to quench while metal nanoparticles with potential metal toxicity are difficult to degrade, both of which have low light-to-heat conversion efficiency, broad spectrum of anti-tumor effects, and lack of tumor targeting specificity. Single-walled carbon nanotubes (SWNTs) can remedy the above inadequacies. Herein, we report our water-soluble, bio-stable and low-toxicity SWNTs with excellent photothermal conversion efficiency. Specific modifications can enable visualization of the aggregate characteristics of SWNTs at the macroscopic or microscopic level in tumors. The dye-conjugated SWNTs bound with targeting antibodies that can induce them specifically targeting to pancreatic tumors for purposes of performing dyes imaging-guided cytotoxic PTT. PTT using this method achieves precise and excellent curative effects with minimal adverse effects, thus providing a promising strategy for anticancer therapy.


Assuntos
Nanotubos de Carbono/química , Imagem Óptica/métodos , Neoplasias Pancreáticas/terapia , Fototerapia/métodos , Receptor IGF Tipo 1/química , Animais , Humanos
20.
J Stat Theory Pract ; 8(3): 444-459, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-38650966

RESUMO

The probability that mortality from certain causes exceeds high thresholds is addressed. An out-of-sample fusion method is presented where an original real data sample is fused or combined with independent computer-generated samples in the estimation of exceedance probabilities assuming a density ratio model. Since the size of the combined sample of real and artificial data is larger than that of the real sample, the fused sample produces short confidence intervals relative to traditional methods. Numerical results show that the method maintains good coverage even for some misspecified cases.

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