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1.
J Cataract Refract Surg ; 50(1): 57-63, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37702453

RESUMEN

PURPOSE: To evaluate the efficacy of topical pilocarpine HCl 1.25% (Pilo) in treating presbyopia in individuals with or without a history of laser vision correction (laser-assisted in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK]). SETTING: Multiple clinical sites. DESIGN: Pooled analysis of 2 identically designed prospective, randomized, vehicle-controlled studies (GEMINI 1 and 2). METHODS: Adults aged 40 to 55 years with presbyopia received once-daily Pilo or vehicle bilaterally for 30 days. Responder rates for ≥3-line improvement in mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) were determined on day 30. RESULTS: Among participants with a history of LASIK/PRK (n = 39 in the Pilo group, n = 41 in the vehicle group), responder rates for ≥3-line improvement in DCNVA on day 30 at hours 0.25, 0.5, 1, 3, 6, 8, and 10, respectively, were 16.7%, 38.9%, 41.7%, 37.8%, 16.2%, 13.9%, and 8.3% with Pilo and 0.0%, 2.6%, 10.5%, 5.1%, 7.7%, 2.6%, and 0.0% with vehicle. Responder rates in the LASIK/PRK subgroup were significantly higher with Pilo than vehicle at hours 0.25 ( P = .0087), 0.5 ( P = .0001), 1 ( P = .0022), and 3 ( P = .0005). In contrast, there were no significant differences in responder rates between Pilo-treated participants with and without LASIK/PRK. Among non-LASIK/PRK participants in the Pilo group (n = 336), responder rates for ≥3-line improvement in DCNVA on day 30 at hours 0.25, 0.5, 1, 3, 6, 8, and 10, respectively, were 16.8%, 32.7%, 39.0%, 28.0%, 17.4%, 12.6%, and 10.5%. CONCLUSIONS: Pilo treatment effectively and similarly improved DCNVA in presbyopes with or without a history of laser vision correction.


Asunto(s)
Queratomileusis por Láser In Situ , Miopía , Queratectomía Fotorrefractiva , Presbiopía , Adulto , Humanos , Pilocarpina/uso terapéutico , Refracción Ocular , Láseres de Excímeros/uso terapéutico , Estudios Prospectivos , Presbiopía/cirugía , Resultado del Tratamiento , Miopía/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
ACS Appl Mater Interfaces ; 16(1): 318-331, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38156407

RESUMEN

Vascular complications caused by diabetes impair the activities of endothelial nitric oxide synthase (eNOS) and cystathionine γ-lyase (CSE), resulting in decreased physiological levels of nitric oxide (NO) and hydrogen sulfide (H2S). The low bioavailability of NO and H2S hinders the endothelialization of vascular grafts. In this study, endothelium-mimicking bilayer vascular grafts were designed with spatiotemporally controlled dual releases of NO and H2S for in situ endothelialization and angiogenesis. Keratin-based H2S donor was synthesized and electrospun with poly(l-lactide-co-ε-caprolactone) (PLCL) as the outer layer of the graft to release H2S. Hyaluronic acid, one of the major glycosaminoglycans in endothelial glycocalyx, was complexed with Cu ions as the inner layer to mimic glutathione peroxidase (GPx) and maintain long-term physiological NO flux. The synergistic effects of NO and H2S of bilayer grafts selectively promoted the regeneration and migration of human umbilical vascular endothelial cells (HUVECs), while inhibiting the overproliferation of human umbilical artery smooth muscle cells (HUASMCs). Bilayer grafts could effectively prevent vascular calcification, reduce inflammation, and alleviate endothelial dysfunction. The in vivo study in a rat abdominal aorta replacement model for 1 month showed that the graft had a good patency rate and had potential for vascular remodeling in situ.


Asunto(s)
Células Endoteliales , Sulfuro de Hidrógeno , Ratas , Humanos , Animales , Óxido Nítrico/farmacología , Sulfuro de Hidrógeno/farmacología , Prótesis Vascular , Endotelio
3.
Insights Imaging ; 14(1): 223, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38129708

RESUMEN

OBJECTIVE: This study aims to compare the feasibility and effectiveness of automatic deep learning network and radiomics models in differentiating low tumor stroma ratio (TSR) from high TSR in pancreatic ductal adenocarcinoma (PDAC). METHODS: A retrospective analysis was conducted on a total of 207 PDAC patients from three centers (training cohort: n = 160; test cohort: n = 47). TSR was assessed on hematoxylin and eosin-stained specimens by experienced pathologists and divided as low TSR and high TSR. Deep learning and radiomics models were developed including ShuffulNetV2, Xception, MobileNetV3, ResNet18, support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), and logistic regression (LR). Additionally, the clinical models were constructed through univariate and multivariate logistic regression. Kaplan-Meier survival analysis and log-rank tests were conducted to compare the overall survival time between different TSR groups. RESULTS: To differentiate low TSR from high TSR, the deep learning models based on ShuffulNetV2, Xception, MobileNetV3, and ResNet18 achieved AUCs of 0.846, 0.924, 0.930, and 0.941, respectively, outperforming the radiomics models based on SVM, KNN, RF, and LR with AUCs of 0.739, 0.717, 0.763, and 0.756, respectively. Resnet 18 achieved the best predictive performance. The clinical model based on T stage alone performed worse than deep learning models and radiomics models. The survival analysis based on 142 of the 207 patients demonstrated that patients with low TSR had longer overall survival. CONCLUSIONS: Deep learning models demonstrate feasibility and superiority over radiomics in differentiating TSR in PDAC. The tumor stroma ratio in the PDAC microenvironment plays a significant role in determining prognosis. CRITICAL RELEVANCE STATEMENT: The objective was to compare the feasibility and effectiveness of automatic deep learning networks and radiomics models in identifying the tumor-stroma ratio in pancreatic ductal adenocarcinoma. Our findings demonstrate deep learning models exhibited superior performance compared to traditional radiomics models. KEY POINTS: • Deep learning demonstrates better performance than radiomics in differentiating tumor-stroma ratio in pancreatic ductal adenocarcinoma. • The tumor-stroma ratio in the pancreatic ductal adenocarcinoma microenvironment plays a protective role in prognosis. • Preoperative prediction of tumor-stroma ratio contributes to clinical decision-making and guiding precise medicine.

4.
Langmuir ; 39(15): 5418-5425, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-37014665

RESUMEN

A protein-polymer conjugate combines the chemical properties of a synthetic polymer chain with the biological properties of a protein. In this study, the initiator terminated with furan-protected maleimide was first synthesized through three steps. Then, a series of zwitterionic poly[3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate] (PDMAPS) was synthesized via atom transfer radical polymerization (ATRP) and optimized. Subsequently, well-controlled PDMAPS was conjugated with keratin via thiol-maleimide Michael addition. The keratin-PDMAPS conjugate (KP) could self-assemble in an aqueous solution to form micelles with low critical micelle concentration (CMC) values and good blood compatibility. The drug-loaded micelles exhibited triple responsiveness to pH, glutathione (GSH), and trypsin under tumor microenvironments. In addition, these micelles showed high toxicity against A549 cells while low toxicity on normal cells. Furthermore, these micelles performed prolonged blood circulation.


Asunto(s)
Portadores de Fármacos , Micelas , Portadores de Fármacos/toxicidad , Portadores de Fármacos/química , Queratinas , Polímeros/química , Citoesqueleto , Sistemas de Liberación de Medicamentos , Concentración de Iones de Hidrógeno , Liberación de Fármacos
5.
Front Bioeng Biotechnol ; 11: 1125348, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36815879

RESUMEN

Although the potential of metal-organic framework (MOF) nanoparticles as drug delivery systems (DDS) for cancer treatment has been established by numerous studies, their clinical applications are still limited due to relatively poor biocompatibility. We fabricated a multifunctional Cu-MOFs@Keratin DDS for loaded drug and chemodynamic therapy (CDT) against tumor cells. The Cu-MOFs core was prepared using a hydrothermal method, and then loaded with the anticancer drug DOX and wrapped in human hair keratin. The Cu-MOFs@Keratin was well characterized by transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS). Characterization and pharmacokinetic studies of Cu-MOFs@Keratin were performed in vitro and in vivo. The keratin shell reduced the cytotoxicity and potential leakage of Cu-MOFs to normal cells, and allowed the drug-loaded nanoparticles to accumulate in the tumor tissues through enhanced permeability and retention effect (EPR). The particles entered the tumor cells via endocytosis and disintegrated under the stimulation of intracellular environment, thereby releasing DOX in a controlled manner. In addition, the Cu-MOFs produced hydroxyl radicals (·OH) by consuming presence of high intracellular levels of glutathione (GSH) and H2O2, which decreased the viability of the tumor cells.

6.
Chin Med Sci J ; 38(1): 62-65, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-36511128

RESUMEN

We report a case of hemophagocytic syndrome (HPS) secondary to brucellosis, in which typhoidal cells were found in bone marrow, suggesting typhoidal cells present not only in Salmonella typhi infections but also in other bacterial infections. Typhoidal cells in bone marrow can be used to quickly identify the presence of bacterial infection pending the results of bone marrow and/or blood cultures.


Asunto(s)
Brucelosis , Linfohistiocitosis Hemofagocítica , Fiebre Tifoidea , Femenino , Humanos , Fiebre Tifoidea/complicaciones , Fiebre Tifoidea/microbiología , Linfohistiocitosis Hemofagocítica/etiología , Brucelosis/complicaciones
7.
Langmuir ; 38(50): 15683-15693, 2022 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-36480797

RESUMEN

Due to thrombosis and intimal hyperplasia, small-diameter vascular grafts have poor long-term patency. A combination strategy based on nitric oxide (NO) and anticoagulants has the potential to address those issues. In this study, poly(ethylene terephthalate) (PET) mats were prepared by electrospinning and coated with tannic acid (TA)/copper ion complexes. The chelated copper ions endowed the mats with sustained NO generation by catalytic decomposition of endogenous S-nitrosothiol. Subsequently, zwitterionic carboxybetaine acrylate (CBA) and argatroban (AG) were immobilized on the mats. The introduced AG and CBA had synergistic effects on the improvement of blood compatibility, resulting in reduced platelet adhesion and prolonged blood clotting time. The biocomposite mats selectively promoted the proliferation and migration of human umbilical vein endothelial cells while inhibiting the proliferation and migration of human umbilical arterial smooth muscle cells under physiological conditions. In addition, the prepared mats exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. Collectively, the prepared mats hold great promise as artificial small-diameter vascular grafts.


Asunto(s)
Cobre , Tereftalatos Polietilenos , Humanos , Células Endoteliales de la Vena Umbilical Humana , Óxido Nítrico/farmacología , Etilenos
8.
Turk J Gastroenterol ; 33(7): 596-605, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35879917

RESUMEN

BACKGROUND: To investigate the relationship between the expression level of hsa-miR-34a-5p and liver injury and to further explore its regulatory signaling pathways Methods: Liver tissue and blood were collected from 60 patients undergoing hepatectomy. We constructed a rat HIRI model and treated it with an intraperitoneal injection of agomir-miR-34a-5p or agomir-normal control (NC) for 7 days after the surgery. The pathological changes of agomir-miR-34a-5p or agomir-normal control (NC) groups were compared. 7702 and AML12 cells were transfected with mimics NC or miR-34a-5p mimics and then treated with H2O2 for 6 hours. Cell apoptosis was detected by flow cytometry, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, respectively. Furthermore, the target genes of miR- 34a-5p were identified by luciferase reporter gene assay and were verified in vitro. RESULTS: The relatively high miR-34a-5p expression group revealed a lower level of alanine aminotransferase and aspartate aminotrans- ferase compared with the relatively low miR-34a-5p expression group. HIRI+agomir-miR-34a-5p rats exhibited significantly higher miR-34a-5p expression, lower serum alanine aminotransferase, aspartate aminotransferase, alleviated hepatic necrosis, reduced hepa- tocyte apoptosis, and decreased expression of apoptosis-related proteins, when compared with HIRI+agomir-NC rats (P < .05). After hydrogen peroxide treatment, alpha mouse liver-12 cell (AML-12) and normal liver cell line LO2 (LO2) cells transfected with miR-34a-5p mimics had significantly lower apoptosis rate compared with miR-34a-5p mimics NC group (P < .05). Hepatocyte nuclear factor 4α was identified as a miR-34a-5p target gene. Hepatocyte nuclear factor 4α expression was significantly downregulated in AML12 and HL-7702 (7702) cells transfected with miR-34a-5p (P < .05). Moreover, AML12 and 7702 cells transfected with miR-34a-5p signifi- cantly showed higher c-Jun N-terminal kinase (JNK), P38, cleavage cas-3, and BCL2 associated X (Bax) protein levels compared with AML12 and 7702 cells transfected with agomir-NC. CONCLUSION: miR-34a-5p possibly protected the liver from I/R injury through downregulating Hepatocyte nuclear factor 4α to inhibit the JNK/P38 signaling pathway.


Asunto(s)
MicroARNs , Daño por Reperfusión , Animales , Apoptosis/genética , Factor Nuclear 4 del Hepatocito , Factores Nucleares del Hepatocito/metabolismo , Peróxido de Hidrógeno/metabolismo , Isquemia/metabolismo , Isquemia/patología , Hígado/patología , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/genética , Daño por Reperfusión/prevención & control
9.
Basic Clin Pharmacol Toxicol ; 131(4): 241-250, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35771163

RESUMEN

BACKGROUND: Glioma is one of the most fatal types of malignant tumours, the cause of which is mostly unknown. Orphan GPCRs (GPRs) have been previously implicated in tumour growth and metastasis. Therefore, these GPRs could prove to be alternative and promising therapeutic targets for cancer treatment. OBJECTIVE: The role of GPR160 in glioma has not yet been assessed. This study aims to explore the association of GPR160 with glioma progression and investigate its role in epithelial-to-mesenchymal transition (EMT) and metastasis. METHODS: Changes in protein expression were assessed using western blot analysis and immunofluorescent staining assays, while mRNA expression changes were evaluated using qRT-PCR. To detect the changes in progression and metastasis, MTT, EdU proliferation, wound healing, transwell migration, and flow cytometry assays were carried out in vitro. An epithelial to mesenchymal phenotypic analysis was performed to detect EMT. RESULTS: We demonstrated that knockdown of GPR160 inhibited proliferation, colony formation, and cell viability and promoted apoptosis. Pro-apoptotic biomarkers were upregulated, while anti-apoptotic biomarkers were downregulated. Cell lines with GPR160 knockdown (GPR160 KD) showed a slowed migration rate and decreased invasion ability. EMT mesenchymal biomarkers were downregulated in GPR160 KD cell lines, while epithelial biomarkers were upregulated. CONCLUSION: This study provides evidence that GPR160 is a potential therapeutic target in glioma for the first time. These findings can be used to discover in detail the molecular mechanism and pathways through which GPR160 promotes glioma progression.


Asunto(s)
Transición Epitelial-Mesenquimal , Glioma , Biomarcadores , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Humanos , ARN Mensajero
10.
J Biomater Sci Polym Ed ; 33(11): 1369-1382, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35319342

RESUMEN

Designing a drug delivery system that is responsive in a tumor microenvironment is important to potentiate the efficacy and reduce the side effects of antitumor drugs. In this study, the surface of mesoporous silica nanoparticles (MSNs) were aminated with 3-aminopropyl triethoxysilane (APTES) and then coupled with keratin, as a gatekeeper, to afford MSNs-NH2@Keratin. The average sizes and morphologies of MSNs and MSNs-NH2@Keratin were characterized with dynamic light scattering and transmission electron microscopy, respectively. The loading content and encapsulation efficiency of doxorubicin (DOX) were calculated to be 17.1 ± 1.7% and 71.3 ± 2.1%. Drug-loaded MSNs-NH2@Keratin exhibited pH and glutathione (GSH) dual responsiveness under tumor microenvironment. The nanoparticles could be uptaken by tumor cells to effectively inhibit tumor cell growth. Moreover, the sizes of nanoparticle were stable in the serum. Collectively, our findings demonstrated the potential of DOX-loaded MSNs-NH2@Keratin in the treatment of cancer.


Asunto(s)
Nanopartículas , Dióxido de Silicio , Doxorrubicina/farmacología , Portadores de Fármacos/farmacología , Sistemas de Liberación de Medicamentos , Glutatión , Concentración de Iones de Hidrógeno , Queratinas , Porosidad
11.
Artículo en Inglés | MEDLINE | ID: mdl-35178106

RESUMEN

BACKGROUND: The occurrence and development of hepatocellular carcinoma (HCC) are closely related to immune function, as is the capacity of hepatoma cells to escape. Immunosurveillance is a key mechanism. Catgut implantation at acupoint (CIAA) is a promising acupuncture improvement method that can regulate immunity and has been widely used in the clinical treatment of a variety of diseases. The aim of this study is to observe the therapeutic effect of CIAA on HCC and to investigate the potential mechanism of immune escape. MATERIALS AND METHODS: A total of 40 mice were randomly divided into three groups: the HCC model group (n = 15), the CIAA treatment group (n = 15), and the control group (n = 10). HCC was chemically induced in 30 mice by the combination of DEN, carbon tetrachloride, and ethanol for 150 days. Among them, 15 were selected for CIAA treatment to ascertain the therapeutic effect. The mRNA expression levels of AFP, IL-10, PD-1, and CTLA-4 in three groups were examined by using RT-PCR. AFP and AKT expressions were measured by using western blotting. PD1, CTLA-4, IL-10, CD4+, and CD8+ protein expression levels were evaluated by using IHC. The mortality rate, body weight, and psychological conditions of three groups were also compared. RESULTS: The mRNA and protein expression levels of AFP, PD-1, CTLA-4, and IL-10 were significantly downregulated in the CIAA-treated mice in comparison with HCC mice. IHC assay shows that CD4+ and CD8+ expression levels were notably upregulated after CIAA treatment. Western blotting assay shows that AKT pathway was deactivated in CIAA-treated mice. CIAA notably reduced the mortality rate and inhibited weight loss caused by HCC and improved the overall psychological condition of the mice. CONCLUSIONS: Taken together, our data corroborate the effective potency of CIAA in the treatment of HCC by and inhibiting immune escape and deactivating the AKT pathway.

12.
Medicine (Baltimore) ; 100(51): e28071, 2021 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-34941046

RESUMEN

ABSTRACT: Few studies have reported an increase in vitamin B12 (VitB12) levels after bariatric surgery. This study reports the phenomenon and adverse reactions of serum VitB12 elevation 1 month after surgery and explores the possible etiologies.Retrospective analysis was performed on VitB12 data for 112 patients from January 2018 to October 2019. Then, 87 patients were included between November 2019 and August 2020. They were divided into 2 groups according to the level of VitB12 after surgery, and the demographic and clinical data were analyzed. Then, LASSO regression model analysis and multiple logistic regression analysis were performed to explore the risk factors for VitB12 elevation after surgery.Retrospective data showed that the VitB12 level was significantly increased 1 month after surgery. Comparison of data between the 2 groups found that more patients also had diabetes in the nonelevated group. The postoperative folic acid and VitB12 levels of the elevated group were significantly higher than those of the nonelevated group. More patients had concurrent constipation in the elevated group than in the nonelevated group. Two meaningful variables in LASSO regression analysis were incorporated into the multivariate logistic regression analysis, and constipation was found to be an independent risk factor for the increase in VitB12 after surgery. Of the 199 patients in this study, 111 patients had elevated VitB12 levels after surgery. Among them, 7 patients had peripheral nerve symptoms.Constipation is an independent risk factor for increased VitB12 levels after surgery. High levels of VitB12 may cause some peripheral nerve symptoms. Therefore, it is necessary to pay attention to patients with postoperative constipation, monitor their VitB12 level as soon as possible, and take measures to improve constipation to avoid some adverse reactions caused by elevated VitB12 levels.


Asunto(s)
Cirugía Bariátrica/efectos adversos , Estreñimiento , Obesidad/cirugía , Vitamina B 12/sangre , Adulto , Estudios de Casos y Controles , Femenino , Ácido Fólico , Humanos , Masculino , Obesidad/sangre , Complicaciones Posoperatorias , Estudios Retrospectivos
13.
China CDC Wkly ; 3(22): 463-467, 2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34594914

RESUMEN

Tobacco smoking is the number one preventable cause of disease and death in China as it is globally. Indeed, the toll of smoking in China is much greater than its status as the world's most populous country. There is a persistent and continuing need for China to implement the measures specified in the global tobacco control treaty, the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC), which China ratified in 2005. The theme for the 2021 WHO World No Tobacco Day focuses on the need to support smoking cessation. This article presents findings from the International Tobacco Control (ITC) Policy Evaluation Project cohort surveys in China, in comparison to ITC cohort surveys in two neighboring countries: Japan and the Republic of Korea. These findings demonstrate that smokers in China very much want to quit, but these intentions are not being translated into quit attempts, relative to smokers in Japan and the Republic of Korea. Additionally, about 80% of Chinese smokers want the Chinese government to do more to control smoking. These findings reaffirm the need for China to implement strong, evidence-based measures to reduce smoking. The objective of Healthy China 2030 to reduce deaths from non-communicable diseases by 30% can be achieved by reducing smoking prevalence from its current 26.6% to 20%, and this reduction can be achieved through strong implementation of FCTC measures.

14.
J Biomater Sci Polym Ed ; 32(15): 1998-2008, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34228943

RESUMEN

A biocompatible hydrogel is ideal for tissue engineering and regeneration. In this study, methacrylated keratin (KerMA) was synthesized for the first time and then blended with poly(ethylene glycol dimethacrylate) (PEGDMA) to form hydrogel through photocrosslinking. The chemical structure, gelation time, swelling behavior, hydrophilicity, cytotoxicity, and 3D printability of PEGDMA/KerMA hydrogels were characterized and exploited. The PEGDMA/KerMA hydrogels performed good cytocompatibility, providing potential applications for tissue engineering and regenerative medicine.


Asunto(s)
Materiales Biocompatibles , Queratinas , Hidrogeles , Polietilenglicoles , Ingeniería de Tejidos
15.
Mediators Inflamm ; 2021: 8876484, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33981184

RESUMEN

Thrombospondin (TSP) proteins have been shown to impact T-cell adhesion, migration, differentiation, and apoptosis. Thrombospondin-1 (TSP-1) is specifically upregulated in several inflammatory diseases and can effectively promote lipopolysaccharide- (LPS-) induced inflammation. In contrast, thrombospondin-2 (TSP-2) has been associated with activation of "anti-inflammatory" T-regulatory cells (Tregs). In this study, we investigated the effects of both TSP-1 and TSP-2 overexpression on macrophage polarization and activation in vitro and in vivo. We analyzed the effects of TSP-1 and TSP-2 on inflammation, vascular endothelial permeability, edema, ultrastructural morphology, and apoptosis in lung tissues of an ARDS mouse model and cultured macrophages. Our results demonstrated that TSP-2 overexpression effectively attenuated LPS-induced ARDS in vivo and promoted M2 macrophage phenotype polarization in vitro. Furthermore, TSP-2 played a role in regulating pulmonary vascular barrier leakage by activating the PI3K/Akt pathway. Overall, our findings indicate that TSP-2 can modulate inflammation and could therefore be a potential therapeutic target against LPS-induced ARDS.


Asunto(s)
Síndrome de Dificultad Respiratoria/prevención & control , Trombospondina 1/fisiología , Trombospondinas/fisiología , Animales , Permeabilidad Capilar , Polaridad Celular , Células Cultivadas , Citocinas/biosíntesis , Terapia Genética , Lipopolisacáridos , Pulmón/patología , Lesión Pulmonar/prevención & control , Macrófagos/fisiología , Ratones , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/fisiología , Síndrome de Dificultad Respiratoria/inducido químicamente
16.
Food Sci Nutr ; 9(5): 2402-2413, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34026059

RESUMEN

Paeonia ludlowii, a plant of the Paeoniaceae family, has abundant genetic diversity in different populations, and the seed oil can be used in a diverse number of activities. However, its neuroprotective effect is not clear. We investigated the memory-improving effects and associated mechanisms of Paeonia ludlowii seed oil (PLSO) on amyloid beta (Aß)25-35-induced Alzheimer's disease (AD) in rats. The Morris water maze test was undertaken, and subsequently, the content of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and acetylcholinesterase (ACHE) in the hippocampus was detected by biochemical analyses. To further study PLSO, we examined the pathologic structure and apoptosis of hippocampal tissue by staining. Immunohistochemical analysis was used to detect expression of IBA-1 and GFAP in the hippocampus. Detection of proinflammatory factors was achieved by reverse transcription-quantitative polymerase chain reaction and Western blotting. High-dose PLSO inhibited expression of GFAP and IBA-1. We demonstrated that high-dose PLSO can regulate activation of glial cells and mediate apoptosis of hippocampal cells, and significantly improve learning and memory deficits in AD rats. PLSO could be developed as a nutritional supplement and sold as a drug for AD prevention and/or treatment.

17.
J Biomater Sci Polym Ed ; 32(9): 1125-1139, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33739232

RESUMEN

Drug-loaded nanoparticles have been widely used in the field of tumor treatment due to their low side effects and reduced frequency of administration. In this study, pH and glutathione (GSH) dual-responsive keratin-tannic acid (TA) complex nanoparticles were established to trigger drug release under tumor microenvironments. Reductive keratin was first extracted using a reduction method. Then, keratin-TA complex nanoparticles (KNPs) were self-assembled via non-covalent interaction and further stabilized by self-crosslinking of thiols. This method was facile and green without chemicals during the whole procedure. KNPs exhibited pH and GSH dual responsiveness as well as charge reversibility in the simulated tumor microenvironment. The anticancer drug of doxorubicin (DOX) was loaded on KNPs by hydrophobicity and hydrogen bonds. Drug-loaded KNPs accelerated drug release under mimicked tumor microenvironments, performing high toxic against A549 cells while low toxic on normal cells. Besides, drug-loaded nanoparticles could be endocytosed by tumor cells. Based on these results, KNPs may serve as drug carriers for therapeutic delivery.


Asunto(s)
Portadores de Fármacos , Nanopartículas , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Glutatión/metabolismo , Concentración de Iones de Hidrógeno , Queratinas , Taninos
18.
Zhongguo Zhong Yao Za Zhi ; 45(18): 4455-4465, 2020 Sep.
Artículo en Chino | MEDLINE | ID: mdl-33164376

RESUMEN

In this paper, the possible molecular mechanism of Forsythia suspensa for the anti-tumor effect was investigated through the network pharmacology and molecular docking. The main components of F. suspensa were obtained by literature mining and TCMSP database. Cancer-related genes were collected with use of GAD and OMIM databases. The interaction network of Compounds-Targets-Pathways was constructed through Cytoscpe software. The targets were analyzed by GO and KEGG means in DAVID database, and the KEGG signal pathways were visualized. Component-Target network analysis results were verified by PyRx molecular docking. The results showed that a total of 26 main components of F. suspensa may act on key targets such as AKT1, IL6, ESR1, EGFR, EGF and CCND1, and were involved in 20 signal pathways. Molecular docking analysis showed that hydrogen bonding, hydrophobic action and Pi-cation bonding maybe the main forms of interaction. In this study, we revealed the anti-tumor effect of F. suspensa through the network of Compounds-Targets-Pathways and molecular docking verification, providing reference and guidance for systematically elucidating the anti-tumor molecular mechanism of the main components of F. suspensa.


Asunto(s)
Medicamentos Herbarios Chinos , Forsythia , Neoplasias , Medicamentos Herbarios Chinos/farmacología , Forsythia/genética , Humanos , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Transducción de Señal
19.
J Oleo Sci ; 69(9): 1001-1009, 2020 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-32788519

RESUMEN

To determine the food potential of Paeonia ludlowii D.Y.Hong (P. ludlowii) kernel oil, in this study, we analysed the fatty acid composition and volatile components of this oil, compared the antioxidant effects of two natural antioxidants on it, and then predicted its shelf life at room temperature (25°C). The results showed that P. ludlowii kernel oil mainly contained 20 fatty acids, of which linoleic acid, oleic acid and other unsaturated fatty acid contents together made up 86.99%. The aromatic composition of the crude P. ludlowii kernel oil was analysed, and 34 aromatic compounds were obtained, including 5 lipids (2.30%), 9 alcohols (12.64%), 6 aldehydes (14.67%), 2 alkanes (1.30%), 5 acids (2.70%), 1 ketone (0.41), 2 alkenes (39.12%) and 4 other substances (26.85%). The effects of the antioxidants were ranked as follows: 0.04% tea polyphenols + crude oil > 0.04% bamboo flavonoids + crude oil > crude oil. In addition, the shelf lives at room temperature (25℃) of each kernel oil-antioxidant mixture were 200.73 d, 134.90 d and 131.61 d, respectively. Overall, these results reveal that P. ludlowii kernel oil is a potential candidate for a new high-grade edible oil, and its development has broad application prospects.


Asunto(s)
Ácidos Grasos Insaturados/análisis , Ácidos Grasos Volátiles/análisis , Calidad de los Alimentos , Almacenamiento de Alimentos , Paeonia/química , Aceites de Plantas/química , Antioxidantes , Ácidos Grasos Insaturados/química , Ácidos Grasos Volátiles/química , Ácido Linoleico/análisis , Ácido Oléico/análisis , Aceites de Plantas/aislamiento & purificación , Temperatura , Factores de Tiempo
20.
J Biomater Sci Polym Ed ; 31(18): 2318-2330, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32729373

RESUMEN

Drug-loaded nanoparticles have been widely used in the field of tumor treatment due to their low side effects and reduced frequency of administration. In this study, keratin-dopamine conjugate was first synthesized by amidation reaction and then formed nanoparticles by self-polymerization of dopamine segment. Keratin-dopamine conjugate nanoparticles (KNPs) exhibited pH and glutathione (GSH) dual responsiveness in the simulated tumor environment. These nanoparticles were able to load anti-cancer drug doxorubicin (DOX) through electrostatic interactions and hydrogen bonds. These drug-loaded KNPs (DKNPs) exhibited controlled drug release in a tumor simulation environment. Meanwhile, DKNPs performed a stronger inhibitory effect on tumor cells compared with human normal tissue cells. Based on the above results, keratin-dopamine conjugate based drug carriers had a broad prospect in the field of cancer treatment.


Asunto(s)
Portadores de Fármacos , Nanopartículas , Dopamina , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Glutatión/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Queratinas
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