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1.
J Agric Food Chem ; 72(20): 11429-11437, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38738769

RESUMO

Platycodon grandiflorus is a medicinal plant whose main component is platycodins, which have a variety of pharmacological effects and nutritional values. The farnesyl pyrophosphate synthase (FPS) is a key enzyme in the isoprenoid biosynthesis pathway, which catalyzes the synthesis of farnesyl diphosphate (FPP). In this study, we cloned the FPS gene from P. grandiflorus (PgFPS) with an ORF of 1260 bp, encoding 419 amino acids with a deduced molecular weight and theoretical pI of 46,200.98 Da and 6.52, respectively. The squalene content of overexpressed PgFPS in tobacco leaves and yeast cells extract was 1.88-fold and 1.21-fold higher than that of the control group, respectively, and the total saponin content was also increased by 1.15 times in yeast cells extract, which verified the biological function of PgFPS in terpenoid synthesis. After 48 h of MeJA treatment and 6 h of ethephon treatment, the expression of the PgFPS gene in roots and stems reached its peak, showing a 3.125-fold and 3.236-fold increase compared to the untreated group, respectively. Interestingly, the expression of the PgFPS gene in leaves showed a decreasing trend after exogenous elicitors treatment. The discovery of this enzyme will provide a novel perspective for enhancing the efficient synthesis of platycodins.


Assuntos
Clonagem Molecular , Geraniltranstransferase , Proteínas de Plantas , Platycodon , Triterpenos , Platycodon/genética , Platycodon/metabolismo , Platycodon/química , Platycodon/enzimologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Geraniltranstransferase/genética , Geraniltranstransferase/metabolismo , Triterpenos/metabolismo , Triterpenos/química , Regulação da Expressão Gênica de Plantas , Sequência de Aminoácidos
2.
Molecules ; 29(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38257334

RESUMO

Trollius chinensis Bunge, a perennial herb belonging to the Ranunculaceae family, has been extensively used in traditional Chinese medicine. Documented in the Supplements to the Compendium of Materia Medica, its medicinal properties encompass a spectrum of applications, including heat clearance, detoxification, alleviation of oral/throat sores, earaches, eye pain, cold-induced fever, and vision improvement. Furthermore, T. chinensis is used in clinical settings to treat upper respiratory infections, pharyngitis, tonsillitis, esoenteritis, canker, bronchitis, etc. It is mainly used to treat inflammation, such as inflammation of the upper respiratory tract and nasal mucosa. This comprehensive review explores the evolving scientific understanding of T. chinensis, covering facets of botany, materia medica, ethnopharmacological use, phytochemistry, pharmacology, and quality control. In particular, the chemical constituents and pharmacological research are reviewed. Polyphenols, mainly flavonoids and phenolic acids, are highly abundant among T. chinensis and are responsible for antiviral, antimicrobial, and antioxidant activities. The flower additionally harbors trace amounts of volatile oil, polysaccharides, and other bioactive compounds. The active ingredients of the flower have fewer side effects, and it is used in children because of its minimal side effects, which has great research potential. These findings validate the traditional uses of T. chinensis and lay the groundwork for further scientific exploration. The sources utilized in this study encompass Web of Science, Pubmed, CNKI site, classic monographs, Chinese Pharmacopoeia, Chinese Medicine Dictionary, and doctoral and master's theses.


Assuntos
Botânica , Materia Medica , Criança , Humanos , Etnofarmacologia , Controle de Qualidade , Inflamação
3.
Biomater Adv ; 158: 213792, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38281322

RESUMO

Posterior capsule opacification (PCO), as one of the most common late complications after intraocular lens (IOL) implantation in cataract surgery, seriously affects patients' postoperative vision and surgical satisfaction, and can only be treated by laser incision of the posterior capsule. Although drug eluting coating modification have been proved to inhibit PCO effectively, the complicated coating methods and the potential toxicity of the antiproliferative drugs hinders its actual application. In this study, an indocyanine green (ICG) loaded polydopamine (PDA) coating modified IOL (IP-IOL) was designed to prevented PCO. In vitro and in vivo studies have shown that IP-IOL can effectively eliminate lens epithelial cells and significantly reduce the degree of PCO. At the same time, it still has good imaging quality and optical properties. Furthermore, both the near-infrared irradiation and ICG loaded PDA coating modified IOLs have proved to possess high biological safety to eyes. Thus, with easy preparation and safer near-infrared irradiated photothermal/photodynamic synchronous properties, such ICG loaded PDA coating provides an effective yet easier and safer PCO prevention after IOL implantation.


Assuntos
Opacificação da Cápsula , Lentes Intraoculares , Polímeros , Humanos , Opacificação da Cápsula/prevenção & controle , Olho Artificial , Indóis/uso terapêutico , Verde de Indocianina/uso terapêutico
4.
J Tradit Chin Med ; 43(6): 1268-1274, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37946490

RESUMO

Acupuncture has been widely used as an alternative and complementary therapy for premature ovarian insufficiency (POI) in China. However, research to date has not shown that acupuncture is effective for POI compared with hormone replacement therapy (HRT). We will conduct a randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on POI. Seventy-six patients with POI will be randomly assigned to two groups. The treatment group will receive twenty-eight one-hour sessions of acupuncture treatments, and the control group will receive 12-week HRT. The whole study will consist of a 12-week treatment plan and a 12-week follow-up session. The primary outcome is measured by changes in serum anti-Müllerian hormone and follicle-stimulating hormone (FSH) levels at weeks 12 and 24. Secondary outcome measures include estradiol, luteinizing hormone (LH), LH/FSH ratio, Kupperman index, and menstrual condition. This trial is expected to clarify whether or not acupuncture is effective and safe for POI compared with HRT.


Assuntos
Terapia por Acupuntura , Insuficiência Ovariana Primária , Feminino , Humanos , Insuficiência Ovariana Primária/terapia , Terapia por Acupuntura/métodos , Estradiol , Hormônio Luteinizante , Hormônio Foliculoestimulante , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
J Gastrointest Surg ; 27(11): 2297-2307, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37715013

RESUMO

PURPOSE: To investigate the efficacy of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (AGC). METHODS: We included 198 patients treated from December 2016 to January 2019; of these patients, the 132 who had clinical T4 gastric cancer were divided into a hyperthermic intraperitoneal chemotherapy group (HIPEC group) and a radical gastrectomy and D2 lymph node dissection group (control group). Because this study was retrospective, we used propensity score matching (PSM) to reduce selectivity bias; we then assessed risk factors for recurrence and compared prognosis in terms of survival in the gastrectomy and prophylactic HIPEC groups. RESULTS: Prophylactic HIPEC reduced the risk of postoperative peritoneal metastasis (PM: 27.5% vs. 10.5%, P = 0.015) and did not increase the risk of postoperative complications, but there was no significant difference in the effect on hepatic metastases or other distant metastases. Risk factors for recurrence included pT4 staging and positive lymph node metastases. Both disease-free survival (DFS: HR 0.592; 95% CI 0.354-0.990; P = 0.042) and peritoneal recurrence-free survival (PFS: HR 0.314; 95% CI 0.127-0.774; P = 0.008) were better in the prophylactic HIPEC group than in the gastrectomy-only group. In addition, there was no difference in the prognosis of patients between the two groups of raltitrexed (RT) and paclitaxel (PTX) for perfusion dosing. CONCLUSION: Our study showed that prophylactic HIPEC could prevent postoperative PM in patients with AGC and did not increase the incidence of postoperative complications. However, it was not found to be effective in the prevention of other metastases, such as hepatic metastases.


Assuntos
Hipertermia Induzida , Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Quimioterapia Intraperitoneal Hipertérmica , Estudos Retrospectivos , Prognóstico , Pontuação de Propensão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Complicações Pós-Operatórias/terapia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Taxa de Sobrevida
6.
J Nanobiotechnology ; 21(1): 323, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679734

RESUMO

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. Drug-eluting intraocular lens (IOLs) is a promising concept of PCO treatment in modern cataract surgery. However, the large dose of drugs in IOL leads to uncontrollable and unpredictable drug release, which inevitably brings risks of overtreatment and ocular toxicity. Herein, a low-power NIR-triggered thermosensitive IOL named IDG@P(NIPAM-co-AA)-IOL is proposed to improve security and prevent PCO by synergetic controlled drug therapy and simultaneous photo-therapy. Thermosensitive polymer brushes Poly(N-isopropylacrylamide-co-Acrylic acid) (P(NIPAM-co-AA)) is prepared on IOL via surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization. Then, Doxorubicin (DOX) and Indocyanine green (ICG) co-loaded Gelatin NPs (IDG NPs) are loaded in P(NIPAM-co-AA) by temperature control. The IDG NPs perform in suit photodynamic & photothermal therapy (PTT&PDT), and the produced heat also provides a trigger for controllable drug therapy with a cascade effect. Such functional IOL shows excellent synergistic drug-phototherapy effect and NIR-triggered drug release behavior. And there is no obvious PCO occurrence in IDG@P(NIPAM-co-AA) IOL under NIR irradiation compared with control group. This proposed IDG@P(NIPAM-co-AA)-IOL serves as a promising platform that combines phototherapy and drug-therapy to enhance the therapeutic potential and medication safety for future clinical application of PCO treatment.


Assuntos
Opacificação da Cápsula , Lentes Intraoculares , Humanos , Opacificação da Cápsula/prevenção & controle , Fototerapia , Terapia Combinada , Doxorrubicina
7.
Food Chem ; 426: 136629, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37331146

RESUMO

In this study, the contamination of 51 mycotoxins in 416 edible oils were determined by UPLC-MS/MS. Totally, twenty-four mycotoxins were detected and nearly half of the samples (46.9%, n = 195) were contaminated simultaneously with six to nine kinds of mycotoxins. The predominant mycotoxins and contamination characteristics varied depending on the type of oils. More specifically, four enniatins, alternariol monomethyl ether (AME) and zearalenone were the most frequent combination. Overall, peanut and sesame oils (10.7-11.7 mycotoxins on average) were found to be the most contaminated matrices whereas camellia and sunflower seed oils (1.8-2.7 species) were the opposite. Dietary exposure risks of mycotoxins were acceptable in most cases, however, the ingestion of aflatoxins (especially aflatoxin B1) through peanut and sesame oil (margin of exposure: 239.4-386.3 < 10000) exceeded the acceptable carcinogenic risk level. Meanwhile, the risks of cumulative ingestion through the food chain should be of great concern, especially sterigmatocystin, ochratoxin A, AME and zearalenone.


Assuntos
Micotoxinas , Zearalenona , Micotoxinas/análise , Zearalenona/análise , Cromatografia Líquida , Espectrometria de Massas em Tandem , Contaminação de Alimentos/análise , Óleos
8.
Am J Cancer Res ; 13(4): 1240-1258, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168356

RESUMO

Pancreatic adenocarcinoma (PAAD) has a poor prognosis and is relatively unresponsive to immunotherapy. Gasdermin C (GSDMC) induces pyroptosis in cancer cells and inflammation in the tumor microenvironment. However, whether GSDMC expression in PAAD is associated with survival or response to immunotherapy remains unknown. GSDMC expression and the relationship between GSDMC and patient survival or immune infiltration in PAAD were examined using data in the The Cancer Genome Atlas (TCGA), Gene Expression Ominbus (GEO), Genotype-Tissue Expression (GTEx) and Cancer Cell Line Encyclopedia (CCLE) databases. The TCGA PAAD cohort could be divided into two distinct risk groups based on the expression of GSDMC-related genes (GRGs). The TIDE algorithm predicted that the low-risk group was more responsive to immune checkpoint blockade therapy than the high-risk group. A novel 15-gene signature was constructed and could predict the prognosis of PAAD. In addition, the 15-gene signature model predicted the infiltration of immune cells and Immune checkpoint blockade (ICB) treatment response. Immunohistochemical staining assessment of patient-derived human tissue microarray (TMA) from 139 cases of local PAAD patients revealed a positive correlation between GSDMC expression and PD-L1 expression but a negative correlation between GSDMC expression and infiltration of low CD8+ T cells. Moreover, the overexpression of GSDMC was related to poor overall survival (OS). This study suggests that GSDMC is a valuable biomarker for predicting PAAD prognosis and predicts the immunotherapy response of PAAD.

9.
J Gastroenterol Hepatol ; 38(9): 1520-1529, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37202867

RESUMO

BACKGROUND AND AIM: Postoperative complications are important clinical outcomes for colon cancer patients. This study aimed to investigate the predictive value of inflammatory-nutritional indicators combined with computed tomography body composition on postoperative complications in patients with stage II-III colon cancer. METHODS: We retrospectively collected data from patients with stage II-III colon cancer admitted to our hospital from 2017 to 2021, including 198 patients in the training cohort and 50 patients in the validation cohort. Inflammatory-nutritional indicators and body composition were included in the univariate and multivariate analyses. Binary regression was used to develop a nomogram and evaluate its predictive value. RESULTS: In the multivariate analysis, the monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), nutritional risk score (NRS), skeletal muscle index (SMI), and visceral fat index (VFI) were independent risk factors for postoperative complications of stage II-III colon cancer. In the training cohort, the area under the receiver operating characteristic curve of the predictive model was 0.825 (95% confidence interval [CI] 0.764-0.886). In the validation cohort, it was 0.901 (95% CI 0.816-0.986). The calibration curve showed that the prediction results were in good agreement with the observational results. Decision curve analysis showed that colon cancer patients could benefit from the predictive model. CONCLUSIONS: A nomogram combining MLR, SII, NRS, SMI, and VFI with good accuracy and reliability in predicting postoperative complications in patients with stage II-III colon cancer was established, which can help guide treatment decisions.


Assuntos
Neoplasias do Colo , Humanos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/cirurgia , Composição Corporal , Inflamação/diagnóstico por imagem , Inflamação/etiologia , Nomogramas , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Tomografia
10.
J Biosci Bioeng ; 134(6): 501-507, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36192322

RESUMO

The present study evaluated the effect of fermentation with Lactiplantibacillus plantarum B7 and Bacillus subtilis natto on phenolic compound levels and enzyme activity, as well as antioxidant capacity of the rose residue. Results showed that the polyphenol content of rose residue was significantly increased from 16.37 ± 1.51 mg/100 mL to 41.02 ± 1.68 mg/100 mL by fermentation at 37 °C and 2.0% (v/v) inoculum size for 40 h. The flavone, soluble dietary, and protein contents were also enhanced by almost 1-fold, 3-fold, and 1-fold, respectively. Fifteen phenolic compounds were quantified in the fermented broth, among which the concentration of gallic acid, quercetin, and p-coumaric acid increased by 5-fold, 4-fold, and almost 8-fold, respectively. Chlorogenic acid was a new phenolic compound produced during fermentation. Moreover, the fermented rose residue presented higher superoxide dismutase, α-amylase, and protease activity. ABTS•+, hydroxylradical, and DPPH• scavenging activity increased by 60.93%, 57.70%, and 37.00%, respectively. This provides an effective means of transforming rose residue into a highly bioactive value-added substance.


Assuntos
Bacillus subtilis , Rosa , Polifenóis
11.
Front Bioeng Biotechnol ; 10: 930540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992334

RESUMO

Posterior capsular opacification (PCO), the highest incidence complication after cataract surgery, is mainly due to the attachment, proliferation, and migration of the residual lens epithelial cells (LECs). Although the drug-eluting IOLs have been proved to be an effective way to prevent PCO incidence, its preparations are time consuming and require tedious preparation steps. Herein, the thermoreversible agarose is adopted to prepare drug-eluting IOL. Such functional coating can be obtained easily by simple immersion in the antiproliferative drug containing hot agarose and taken out for cooling, which not only does not affect the optical property but also can effectively decrease the PCO incidence after intraocular implantation. As a result, the proposed agarose coating provides a rapid and economical alternative of drug-eluting IOL fabrication for PCO prevention.

12.
Adv Sci (Weinh) ; 9(18): e2200670, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35478383

RESUMO

Natural tissues are composed of ordered architectural organizations of multiple tissue cells. The spatial distribution of cells is crucial for directing cellular behavior and maintaining tissue homeostasis and function. Herein, an artificial bone bioceramic scaffold with star-, Tai Chi-, or interlacing-shaped multicellular patterns is constructed. The "cross-talk" between mesenchymal stem cells (MSCs) and macrophages can be effectively manipulated by altering the spatial distribution of two kinds of cells in the scaffolds, thus achieving controllable modulation of the scaffold-mediated osteo-immune responses. Compared with other multicellular patterns, the Tai Chi pattern with a 2:1 ratio of MSCs to macrophages is more effective in activating anti-inflammatory M2 macrophages, improving MSCs osteogenic differentiation, and accelerating new bone formation in vivo. In brief, the Tai Chi pattern generates a more favorable osteo-immune environment for bone regeneration, exhibiting enhanced immunomodulation and osteogenesis, which may be associated with the activation of BMP-Smad, Oncostatin M (OSM), and Wnt/ß-catenin signaling pathways in MSCs mediated by macrophage-derived paracrine signaling mediators. The study suggests that the manipulation of cell distribution to improve tissue formation is a feasible approach that can offer new insights for the design of tissue-engineered bone substitutes with multicellular interactions.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Materiais Biocompatíveis , Regeneração Óssea , Diferenciação Celular , Osteogênese/fisiologia
13.
Biofabrication ; 13(4)2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34340226

RESUMO

Elimination of residual osteosarcoma cells and repair of bone defects remain major challenges for osteosarcoma in clinic. To address this problem, it is required that multifunctional therapeutic platform possess high tumor-killing efficiency and simultaneous bone regeneration capabilities. In this work, an intelligent therapeutic platform was developed to achieve highly-efficient tumor therapy and simultaneous significantly improved bone defect repairing ability, which was realized byin situgrowing ferromagnetic Fe3S4layers with tuned microstructures on the surface of 3D-printed akermanite bioceramic scaffolds via hydrothermal method. The Fe3S4layers exploited magnetic thermal energy to enhance chemodynamic treatment, thus achieving a synergistic effect between magnetothermal and chemodynamic therapy on the elimination of residual tumor cells. Moreover, the micro-structured surface of the 3D-printed bioceramic scaffolds further enhanced the osteogenic activityin vitroand accelerated the bone regenerationin vivo. The scaffolds with multi-mode tumor-killing and bone repairing capabilities indicated that such a therapeutic platform is applicable for a stepwise treatment strategy of osteosarcoma and provides inspiration for the design of multifunctional biomaterials.


Assuntos
Neoplasias Ósseas , Alicerces Teciduais , Materiais Biocompatíveis , Neoplasias Ósseas/tratamento farmacológico , Regeneração Óssea , Humanos , Osteogênese , Impressão Tridimensional
14.
J Mater Chem B ; 9(21): 4355-4364, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34013948

RESUMO

Although calcium phosphate cements (CPCs) have been clinically used to repair bone defects caused by bone tumor resection, traditional CPCs cannot kill the remaining tumor cells after surgery and prevent cancer recurrence. In this study, a multifunctional injectable metal-organic framework (MOF) cobalt coordinated tetrakis(4-carboxyphenyl)porphyrin (Co-TCPP)-modified calcium phosphate cement (Co-TCPP/CPC) was prepared for the minimally invasive treatment of neoplastic bone defects. The incorporation of Co-TCPP not only retained the good injectability of bone cements, but also shortened the setting time, improved the compressive strength, and endowed them with excellent photothermal properties. The hyperthermia effect induced by the presence of Co-TCPP well induced the therapeutic effect against bone tumors both in vitro and in vivo. Moreover, Co-TCPP/CPC exhibited desirable osteogenesis and angiogenesis by promoting bone and vascular regeneration in vivo. Therefore, the Co-TCPP composite bone cement demonstrated its great potential for bone tumor therapy and tissue regeneration, representing a multifunctional biomaterial for the treatment of neoplastic bone defects.


Assuntos
Cimentos Ósseos , Regeneração Óssea , Neoplasias/patologia , Materiais Biocompatíveis , Humanos
15.
Food Chem ; 347: 129006, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33472117

RESUMO

Multilayer bottles consisting of chitosan (CS), microcrystalline cellulose (MCC), whey protein isolate (WPI), and polyethylene terephthalate (PET) were tested as novel materials for packaging and extending shelf life of rosebud beverages. We studied the storage stability at 4 °C, 25 °C, 37 °C, and 55 °C by assessing the physical and biochemical parameters. The results show that multilayer PET bottles had better barrier performance and improved soluble solids content, pH, polyphenol content, color indices, and browning degree in rosebud beverages over the control at all studied temperatures. A shelf life model was established based on the Arrhenius equation, and the number of days when polyphenol contents dropped to <50% of the initial content was defined as the shelf life. Our results highlight the reliability of the prediction model, and we conclude that packaging rosebud beverages in multilayer PET bottles significantly extends the product shelf life, and this benefit was further extended at low temperatures.


Assuntos
Bebidas/análise , Celulose/química , Quitosana/química , Embalagem de Alimentos/métodos , Polietilenotereftalatos/química , Proteínas do Soro do Leite/química , Cor , Armazenamento de Alimentos , Concentração de Íons de Hidrogênio , Polifenóis/química , Temperatura
16.
J Mater Chem B ; 9(3): 793-800, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33336672

RESUMO

Drug-loaded intraocular lenses (IOLs) have received considerable attention in treating complications that arise after cataract surgery, especially posterior capsular opacification (PCO). However, for a better therapeutic effect, the drug concentration in IOLs usually needs to be increased. Herein, we developed multilayer (doxorubicin (DOX)@polyaminoamide (PAMAM) (D@P)/heparin sodium (HEP))5 modified IOLs, which efficiently enhance the inhibitory effect on PCO using the enhanced autophagy effect of a cationic PAMAM. The chemotherapeutic drug DOX was encapsulated in PAMAM to formulate cationic DOX@PAMAM nanoparticles. Subsequently, negatively charged HEP and D@P nanoparticles (NPs) were assembled on the aminated artificial IOL surface using the layer-by-layer (LBL) assembly technique. The (D@P/HEP)5 IOLs were implanted into rabbit eyes to evaluate the prevention of PCO. In vitro and in vivo research studies showed that the D@P NPs exhibited enhanced cellular uptake owing to the cell-penetrating cationic characteristics, while demonstrating enhanced autophagy. D@P NPs are more effective at the same DOX concentration when compared to free DOX. Multilayer-modified (D@P/HEP)5 IOLs can efficiently inhibit PCO after cataract surgery. This study provides a strategy for improving the therapeutic effect of antiproliferative drug DOX by using a cationic dendrimer, which, in turn, increases the level of autophagy of cells. These LBL-based multilayer IOLs have broad application prospects in the treatment of complications after cataract surgery.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Opacificação da Cápsula , Doxorrubicina/farmacologia , Implante de Lente Intraocular/efeitos adversos , Cápsula Posterior do Cristalino , Animais , Antibióticos Antineoplásicos/administração & dosagem , Autofagia/efeitos dos fármacos , Opacificação da Cápsula/prevenção & controle , Opacificação da Cápsula/cirurgia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dendrímeros/administração & dosagem , Dendrímeros/farmacologia , Doxorrubicina/administração & dosagem , Endocitose/efeitos dos fármacos , Heparina/administração & dosagem , Heparina/farmacologia , Humanos , Tamanho da Partícula , Poliaminas/administração & dosagem , Poliaminas/farmacologia , Cápsula Posterior do Cristalino/efeitos dos fármacos , Cápsula Posterior do Cristalino/cirurgia , Coelhos , Propriedades de Superfície
17.
Sci Adv ; 6(12): eaaz6725, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32219170

RESUMO

The integration of structure and function for tissue engineering scaffolds is of great importance in mimicking native bone tissue. However, the complexity of hierarchical structures, the requirement for mechanical properties, and the diversity of bone resident cells are the major challenges in constructing biomimetic bone tissue engineering scaffolds. Herein, a Haversian bone-mimicking scaffold with integrated hierarchical Haversian bone structure was successfully prepared via digital laser processing (DLP)-based 3D printing. The compressive strength and porosity of scaffolds could be well controlled by altering the parameters of the Haversian bone-mimicking structure. The Haversian bone-mimicking scaffolds showed great potential for multicellular delivery by inducing osteogenic, angiogenic, and neurogenic differentiation in vitro and accelerated the ingrowth of blood vessels and new bone formation in vivo. The work offers a new strategy for designing structured and functionalized biomaterials through mimicking native complex bone tissue for tissue regeneration.


Assuntos
Regeneração Óssea , Ósteon , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Materiais Biocompatíveis/química , Biomimética , Diferenciação Celular , Técnicas de Cocultura , Células Endoteliais da Veia Umbilical Humana , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Neurogênese , Osteogênese , Porosidade
18.
ACS Appl Bio Mater ; 3(6): 3582-3593, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35025228

RESUMO

Posterior capsular opacification (PCO) is a common complication after cataract surgery, which often leads to a progressive decline in the patient's vision. It has been established that PCO is related to the adhesion and proliferation of the residual lens epithelial cells (LECs) on the implanted intraocular lens (IOL) after surgery, which blocks visual pathways again. It has been reported that matrix metalloproteinases (MMPs) are greatly up-regulated in the LEC proliferation process. In the present study, an antiproliferative drug, functionalized poly(ethylene glycol) methacrylate (PEGMA), was synthesized using a MMP-2 sensitive peptide as a linkage. This PEGMA derivative polymerizable molecule was then immobilized onto the IOL surface via surface initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization, which resulted in hydrophilic and MMP-2 sensitive drug eluting coatings on the IOL. The in vitro results show that LEC proliferation is inhibited in the presence of enzyme. The in vivo animal experiments with such surface modified IOLs not only indicate significant PCO prevention but also show excellent intraocular biocompatibility with adjacent tissues. All these results suggest that this hydrophilic and MMP-2 sensitive drug eluting surface coating would be a promising way to prevent PCO.

19.
Int J Nanomedicine ; 14: 9047-9061, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819418

RESUMO

BACKGROUND: Posterior capsular opacification (PCO) is the main complication after intraocular lens (IOL) implantation in cataract surgery, which is the result of lens epithelial cell (LEC) adhesion, proliferation and migration on the IOL and at the lens capsule interface. Hydrophilic surface modification, such as surface heparinization, decreases the cell adhesion, which has been commercialized and used clinically. However, clinical long-term observation results show no significant difference between the pristine and heparinized IOLs. METHODS: To prevent PCO over the long time span, we modified the IOLs with an antiproliferative drug-loaded hydrophilic coating. The antiproliferative drug doxorubicin (DOX)-incorporated chitosan (CHI) nanoparticle was fabricated by sodium tripolyphosphate (TPP) gelation. Such antiproliferative drug-loaded CHI-TPP-DOX nanoparticles (CTDNP) were used as one of the building blocks to prepare polyelectrolyte multilayer with heparin (HEP) via layer-by-layer assembly, obtaining (HEP/CTDNP)n multilayers. The assembly process was characterized by quartz crystal microbalance with dissipation (QCM-D). The drug release behavior of the coating was investigated by ultra-HPLC (UPLC). In vitro cell experiments were carried out to monitor the effects of multifunctional coatings on cellular adhesion, proliferation and migration. And the intraocular implantation was performed on rabbits to evaluate the in vivo PCO inhibitory effect of such surface-functionalized IOLs. RESULTS: The positively charged CTDNP was successfully prepared by ionic gelation. The QCM-D results indicate the successful preparation of the (HEP/CTDNP)n multilayer film. Drug release profiles showed that surface-multifunctionalized IOL had drug-sustained release properties. In vitro cell culture results showed significant inhibition of adhesion, proliferation and migration of LECs after surface modification. The in vivo results showed that the IOLs with multifunctionalized surface can effectively reduce the posterior hyperplasia and Soemmering's ring (SR) formation. CONCLUSION: These findings suggested that such multifunctionalized drug-eluting IOLs can effectively reduce the posterior hyperplasia and SR formation when intraocular implantation has a major impact on reducing PCO incidence. Thus they have a great potential in improving patient vision recovery and maintenance.


Assuntos
Catarata/patologia , Lentes Intraoculares , Cápsula Posterior do Cristalino/patologia , Adesivos/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Quitosana/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Nanopartículas/química , Tamanho da Partícula , Cápsula Posterior do Cristalino/efeitos dos fármacos , Técnicas de Microbalança de Cristal de Quartzo , Coelhos , Eletricidade Estática , Propriedades de Superfície
20.
Curr Mol Med ; 20(1): 51-59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31533600

RESUMO

PURPOSE: Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determine the physiological relevance of PIDD in RGCs apoptosis in an optic nerve crush (ONC) model. METHODS: All animals were evenly randomized into four groups: sham-control group, con-siRNA group, ONC group, and PIDD-siRNA group (ONC +PIDD-siRNA). Expressions of PIDD, caspase-2, Brn3a and tBid in ONC model were analyzed by Western blot and immunofluorescence. Mean densities of RGCs/mm2 were calculated with Fluoro-Gold (FG). Moreover, we tested the effect of PIDD-siRNA on ONC-induced RGCs apoptosis using TUNEL staining. RESULTS: The level of full-length PIDD was weakly present and showed no significant differences at any time points. PIDD-CC and PIDD-C were significantly up-regulated in the retina at 3 days after ONC. Meanwhile, the expression of PIDD was significantly increased in Brn3a (a marker of RGCs) positive cells, indicating that the localization of PIDD appeared to be confined to RGCs. Furthermore, inhibition of PIDD prevented RGCs apoptosis by inhibiting caspase-2 and tBid activation. CONCLUSION: Taken together, PIDD may play a crucial role in RGCs apoptosis after ONC, and this process may be relevant to caspase-2 and tBid.


Assuntos
Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/genética , Caspase 2/genética , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/genética , Nervo Óptico/metabolismo , Células Ganglionares da Retina/metabolismo , Animais , Apoptose/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Compressão Nervosa/métodos , Nervo Óptico/patologia , RNA Interferente Pequeno/genética , Ratos , Células Ganglionares da Retina/patologia , Proteína Supressora de Tumor p53/genética
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