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1.
Signal Transduct Target Ther ; 7(1): 263, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35927231

RESUMO

Psoriasis is a common, chronic immune-mediated systemic disease that had no effective and durable treatment. Mesenchymal stem cells (MSCs) have immunomodulatory properties. Therefore, we performed a phase 1/2a, single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs (UMSCs) in the treatment of psoriasis and to preliminarily explore the possible mechanisms. Seventeen patients with psoriasis were enrolled and received UMSC infusions. Adverse events, laboratory parameters, PASI, and PGA were analyzed. We did not observe obvious side effects during the treatment and 6-month follow-up. A total of 47.1% (8/17) of the psoriasis patients had at least 40% improvement in the PASI score, and 17.6% (3/17) had no sign of disease or minimal disease based on the PGA score. And the efficiency was 25% (2/8) for males and 66.7% (6/9) for females. After UMSC transplantation (UMSCT), the frequencies of Tregs and CD4+ memory T cells were significantly increased, and the frequencies of T helper (Th) 17 and CD4+ naive T cells were significantly decreased in peripheral blood (PB) of psoriasis patients. And all responders showed significant increases in Tregs and CD4+ memory T cells, and significant decreases in Th17 cells and serum IL-17 level after UMSCT. And baseline level of Tregs in responders were significantly lower than those in nonresponders. In conclusion, allogeneic UMSCT is safe and partially effective in psoriasis patients, and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT. Trial registration Clinical Trials NCT03765957.


Assuntos
Células-Tronco Mesenquimais , Psoríase , Feminino , Humanos , Masculino , Prostaglandinas A/uso terapêutico , Psoríase/tratamento farmacológico , Resultado do Tratamento , Cordão Umbilical
3.
Medicine (Baltimore) ; 101(26): e29770, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35776992

RESUMO

BACKGROUND: As a relatively minimally invasive technique, endoscopic submucosal dissection (ESD) is widely used for the treatment of gastrointestinal lesions. However, it is associated with complications, such as postoperative bleeding, stricture, and perforation. A covering method using polyglycolic acid (PGA) sheets for ESD-induced ulcers has been reported to be effective in reducing the risk of post-ESD bleeding and esophageal stricture. Herein, we conducted a systematic review and meta-analysis to evaluate the role of PGA sheets in the prevention of gastrointestinal bleeding and esophageal stricture after ESD. METHODS: We searched PubMed, Web of Science, and the Cochrane Library databases on October 15, 2019. All eligible articles were selected based on the predefined inclusion and exclusion criteria. The main outcomes were the rates of post-ESD gastrointestinal bleeding and esophageal stricture. Cochrane's Q statistic and I2 test were used to identify heterogeneity between the studies. When there was no obvious heterogeneity (I2 < 50%, P > .1), a fixed-effect model was used. When there was obvious heterogeneity (I2 > 50%, P < .1), a random effect model was used. Funnel plots and the Egger regression test were used to assess publication bias. RESULTS: Fifteen articles were included in the meta-analysis, of which 7 were exclusively about the use of PGA sheets to prevent postoperative gastrointestinal bleeding, and the remaining reported the use of PGA sheets to prevent postoperative esophageal stenosis. Our analysis showed that preventive therapy with PGA sheets decreased the rates of post-ESD gastrointestinal bleeding (risk ratio [RR] = 0.35, 95% confidential interval [CI]: 0.19-0.64, P < .001) and esophageal stricture (RR = 0.46, 95% CI: 0.27-0.79, P = .005), and the gastrointestinal bleeding and esophageal stricture rates after preventive treatment with PGA sheets were 5.7% (95% CI: 3.6%-8.8%) and 20.6% (95% CI: 14.5%-28.4%), respectively. CONCLUSION: The utilization of PGA sheets after ESD has an excellent outcome in reducing the risk of postoperative gastrointestinal bleeding and esophageal stricture.


Assuntos
Ressecção Endoscópica de Mucosa , Estenose Esofágica , Adesivos Teciduais , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Estenose Esofágica/etiologia , Estenose Esofágica/prevenção & controle , Estenose Esofágica/cirurgia , Adesivo Tecidual de Fibrina , Hemorragia Gastrointestinal/complicações , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Ácido Poliglicólico/uso terapêutico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Prostaglandinas A
4.
Nutrients ; 14(14)2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35889874

RESUMO

Oxidative stress and inflammation play a pivotal role in the development of cardiovascular diseases, an ever-growing worldwide problem. As a non-pharmacological approach, diet, especially a flavonoid-rich diet, showed promising results in the reduction of cardiovascular diseases and alleviation of their symptoms. In this study, in vitro systems based on human microvascular endothelial cells (hmvEC) and human umbilical cord endothelial cells (HUVEC) were established to determine the effect of Healthberry 865® (HB) and ten of its relating single anthocyanins on oxidative stress. Furthermore, five metabolites were used in order to examine the effect of anthocyanin's most common breakdown molecules. The results showed an effect of HB in both models after 24 h, as well as most of its single anthocyanins. Cyanidin-rutinoside, peonidin-galactoside, and petunidin-glucoside had a model-specific effect. For the metabolites, phloroglucinaldeyhde (PGA) showed an effect in both models, while vanillic acid (VA) only had an effect in HUVEC. When combined, a combination of several anthocyanins did not have a cumulative effect, except for combining glucosides in hmvEC. The combination of PGA and VA even revealed an inhibitive behavior. Overall, the study demonstrates the antioxidative effect of HB and several of its single anthocyanins and metabolites, which are partially model specific, and coincides with animal studies.


Assuntos
Antocianinas , Doenças Cardiovasculares , Animais , Antocianinas/metabolismo , Antocianinas/farmacologia , Células Endoteliais/metabolismo , Glucosídeos/farmacologia , Humanos , Estresse Oxidativo , Prostaglandinas A/metabolismo
5.
Chest ; 161(6): e337-e341, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35680312

RESUMO

In critically ill patients receiving mechanical ventilation, expiratory muscles are recruited with high respiratory loading and/or low inspiratory muscle capacity. In this case report, we describe a previously unrecognized patient-ventilator dyssynchrony characterized by ventilator triggering by expiratory muscle relaxation, an observation that we termed expiratory muscle relaxation-induced ventilator triggering (ERIT). ERIT can be recognized with in-depth respiratory muscle monitoring as (1) an increase in gastric pressure (Pga) during expiration, resulting from expiratory muscle recruitment; (2) a drop in Pga (and hence, esophageal pressure) at the time of ventilator triggering; and (3) diaphragm electrical activity onset occurring after ventilator triggering. Future studies should focus on the incidence of ERIT and the impact in the patient receiving mechanical ventilation.


Assuntos
Doenças Neuromusculares , Prostaglandinas A , Expiração/fisiologia , Humanos , Relaxamento Muscular , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Músculos Respiratórios/fisiologia , Ventiladores Mecânicos
6.
Drug Deliv ; 29(1): 1994-2001, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35762638

RESUMO

Neointimal hyperplasia is a complex process after vascular interventions, acute platelet deposition and smooth muscle cell proliferation both contributed to this process. There are still no perfect solutions to solve this problem. Rivaroxaban is a novel anticoagulant that has been widely used in clinic, it has a good pharmacological effects both in vivo and in vitro. Chitosan microparticle rapamycin (MP-rapa) was fabricated, interspaces of polyglycolic acid (PGA) scaffold were used as a reservoir of MP-rapa, and the scaffold was coated with hyaluronic acid rivaroxaban (MP-rapa-riva). Scanning electronic microscopy (SEM) photographs were taken and water contact angles were measured, rat inferior vena cava (IVC) patch venoplasty model was used; patches were harvested at day 14 and examined by immunohistochemistry and immunofluorescence. SEM photographs showed the microparticles rapamycin were inside the interspace of the scaffold, hyaluronic acid rivaroxaban was also successfully coated onto the surface of the scaffold. There was a thinner neointima, fewer proliferating cell nuclear antigen (PCNA) positive cells, fewer macrophages in the MP-rapa and MP-rapa-riva grafts compared to the control PGA graft. The result showed that this scaffold with dual anticoagulation and antiproliferation functions can effectively inhibit venous neointimal hyperplasia, although this is an animal experiment, it showed promising potential clinical application in the future.


Assuntos
Quitosana , Neointima , Animais , Quitosana/farmacologia , Ácido Hialurônico/farmacologia , Hiperplasia/tratamento farmacológico , Hiperplasia/patologia , Neointima/patologia , Prostaglandinas A/farmacologia , Ratos , Rivaroxabana/farmacologia , Sirolimo/farmacologia , Túnica Íntima/patologia
7.
Molecules ; 27(12)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35744931

RESUMO

Prostaglandin (PG) A2, a cyclopentenone PG, induced apoptosis in both HCT116 and HCT116 p53 -/- cells. Although PGA2-induced apoptosis in HCT116 cells was dependent on the p53-DR5 pathway, the mechanism underlying PGA2-induced apoptosis in HCT116 p53 -/- cells remains unknown. In this study, we observed that PGA2 caused an increase of mRNA expression of DR5 and protein expression even in HCT116 p53 -/- cells, accompanied by caspase-dependent apoptosis. Knockdown of DR5 expression by RNA interference inhibited PGA2-induced apoptosis in HCT116 p53 -/- cells. Parallel to the induction of apoptosis, PGA2 treatment upregulated expression of genes upstream of DR5 such as ATF4 and CHOP. Knockdown of CHOP prevented DR5-dependent cell death as well as the expression of DR5 protein. Furthermore, knockdown of ATF4 by RNA interference decreased both mRNA and protein levels of CHOP and DR5, thereby suppressing PGA2-induced cell death. Consistently, the DR5 promoter activity increased by PGA2 was not stimulated when the CHOP binding site in the DR5 promoter was mutated. These results collectively suggest that PGA2 may induce DR5-dependent apoptosis via the ATF4-CHOP pathway in HCT116 p53 null cells.


Assuntos
Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Apoptose , Linhagem Celular Tumoral , Células HCT116 , Humanos , Prostaglandinas A , RNA Mensageiro , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
8.
Nutrients ; 14(12)2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35745126

RESUMO

Food fortification and folic acid supplementation during pregnancy have been implemented as strategies to prevent fetal malformations during pregnancy. However, with the emergence of conditions where folate metabolism and transport are disrupted, such as folate receptor alpha autoantibody (FRαAb)-induced folate deficiency, it is critical to find a folate form that is effective and safe for pharmacologic dosing for prolonged periods. Therefore, in this study, we explored the absorption and tissue distribution of folic acid (PGA), 5-methyl-tetrahydrofolate (MTHF), l-folinic acid (levofolinate), and d,l-folinic acid (Leucovorin) in adult rats. During absorption, all forms are converted to MTHF while some unconverted folate form is transported into the blood, especially PGA. The study confirms the rapid distribution of absorbed folate to the placenta and fetus. FRαAb administered, also accumulates rapidly in the placenta and blocks folate transport to the fetus and high folate concentrations are needed to circumvent or overcome the blocking of FRα. In the presence of FRαAb, both Leucovorin and levofolinate are absorbed and distributed to tissues better than the other forms. However, only 50% of the leucovorin is metabolically active whereas levofolinate is fully active and generates higher tetrahydrofolate (THF). Because levofolinate can readily incorporate into the folate cycle without needing methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) in the first pass and is relatively stable, it should be the folate form of choice during pregnancy, other disorders where large daily doses of folate are needed, and food fortification.


Assuntos
Ácido Fólico , Prostaglandinas A , Animais , Suplementos Nutricionais , Feminino , Leucovorina , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Gravidez , Prostaglandinas A/metabolismo , Ratos , Tetra-Hidrofolatos/metabolismo , Distribuição Tecidual
9.
Carbohydr Polym ; 291: 119521, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35698365

RESUMO

Polygalacturonic acid (PGA), being the backbone of pectins, governs their aggregation that is widely applied in industry. The PGA aggregation was studied by dynamic and static light scattering within a limited space of sodium polygalacturonate nanoparticles obtained by nanoprecipitation (drop-wise addition of alkaline solution of PGA to an ethanol bath). With increasing buffer's pH from 4.0 to 9.1, the colloids changed their form from elongated to spherical one, as indicated by decreasing the structure-sensitive ratio Rg/Rh from 1.7 to 1.1. Molecular mass-per-unit-length determined in Holtzer coordinates decreased from 5000 to 1600 Da nm-1 with increasing pH, suggesting partial disintegration of helical bundles due to electrostatic repulsion. Kratky plots also pointed out partial disintegration of the PGA junctions with increasing pH. Nonmonotonic dependence of the colloidal radius of gyration Rg on [NaCl] characterized the osmotic regime characteristic of annealed polyelectrolytes and thus confirmed the star-like structure of junctions.


Assuntos
Nanopartículas , Prostaglandinas A , Coloides/química , Pectinas , Espalhamento de Radiação
10.
Int J Biol Macromol ; 213: 1057-1067, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35691429

RESUMO

This study aimed to prepare alcohol-free curcumin-loaded zein-propylene glycol alginate (zein-PGA-Cur) nanoparticles using the pH-driven method to enhance the bioavailability and physicochemical stability of curcumin. The prepared zein-PGA-Cur nanoparticles exhibited a small size (360 nm) and negative zeta-potential (-5.8 mV), as well as excellent physical stability, under storage conditions of pH 4.0 and temperature at 4 °C for 30 days. In addition, the Fourier transform infrared spectroscopy results demonstrated that the main interactions of pH-driven for the formation of zein-PGA-Cur nanoparticles were hydrogen bonding, hydrophobic, and electrostatic interactions. Fluorescence spectroscopy revealed that the curcumin-induced fluorescence quenching of zein was static. Circular Dichroism spectroscopy demonstrated that the pH-driven method mainly decreased the ß-sheet structure of zein from 3.9 % to 1.4 %. Furthermore, the HT-29 colorectal adenocarcinoma cells viability experiments revealed that the prepared zein-PGA-Cur nanoparticles exhibited excellent biocompatibility. In vivo rat experiments also demonstrated that the prepared nanoparticles resulted in a higher plasma concentration of curcumin, representing a 7.2-fold enhancement in bioavailability compared with pure curcumin crystals. The findings of this study will provide a green and energy-saving method for the development of insoluble drug self-assembly systems and promote their wider applications in drug delivery.


Assuntos
Curcumina , Nanopartículas , Zeína , Alginatos , Animais , Curcumina/química , Curcumina/farmacologia , Etanol , Concentração de Íons de Hidrogênio , Nanopartículas/química , Tamanho da Partícula , Prostaglandinas A , Ratos , Zeína/química
11.
Food Res Int ; 157: 111387, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35761643

RESUMO

Propylene glycol alginate (PGA) was added to improve the stability and delivery performance of carboxymethyl starch (CMS)-stabilized emulsion. In the first instance, the CMS/PGA complexes were characterized, which proved that the formation of CMS/PGA complexes mainly depended on hydrogen bonding, and the CMS/PGA complexes showed porous networks. The CMS/PGA complexes were more hydrophobic than CMS, and the interaction of CMS with PGA enhanced the thermal stability of CMS. Next, the effects of CMS/PGA complexes on the properties of emulsions were investigated, and the intestine-targeted delivery potential of emulsions was evaluated through the in vitro release study as well. The droplet size of CMS/PGA complex-stabilized emulsions gradually decreased and the encapsulation efficiency (EE) improved with increasing the PGA content in CMS/PGA complexes. The addition of PGA also greatly improved the physical stability of emulsions, including anti-flocculation and anti-coalescence stabilities. All emulsions exhibited non-Newtonian pseudoplastic properties. Furthermore, the emulsions stabilized by CMS/PGA complexes showed reduced curcumin (Cur) release in the simulated gastric fluid (SGF), whereas exhibited sustained release in the α-amylase-containing simulated intestinal fluid (SIF). These results demonstrated that the emulsion stabilized by CMS/PGA complex was able to control and modulate the release of Cur in the gastrointestinal tract, and was therefore a promising intestine-targeted delivery system for Cur.


Assuntos
Curcumina , Prostaglandinas A , Alginatos , Curcumina/química , Emulsões/química , Intestinos , Amido/análogos & derivados
12.
Biomater Sci ; 10(15): 4218-4227, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35748430

RESUMO

Rapidly in situ forming adhesive hydrogels are promising candidates for efficient hemostasis due to their easy administration and minimal invasion. However, development of biocompatible and high-performance hemostatic hydrogels without any additional toxic agents remains a challenge. Herein, a series of novel injectable adhesive hydrogels based on N-hydroxysuccinimide (NHS) modified γ-poly(glutamic acid) (γPGA-NHS) and tetra-armed poly(ethylene glycol) amine (Tetra-PEG-NH2) were developed. Among all samples, PGA10-PEG15 and PGA10-PEG20 hydrogels with higher PEG contents exhibited rapid gelation time (<20 s), strong mechanical strength (compression modulus up to ∼75 kPa), good adhesive properties (∼15 kPa), and satisfactory burst pressure (∼18-20 kPa). As a result, PGA10-PEG15 and PGA10-PEG20 hydrogels showed a remarkable reduction in hemostasis time and blood loss compared with gauze and fibrin glue. More importantly, the PGA10-PEG20 hydrogel was also successfully used to seal femoral arterial trauma. Subcutaneous implantation experiments indicated a good biocompatibility of the hydrogels in vivo. All these results strongly support that the developed PGA-PEG hydrogels could serve as promising hemostatic agents in emergency and clinical situations.


Assuntos
Hemostáticos , Hidrogéis , Adesivos , Ácido Glutâmico , Hemorragia/tratamento farmacológico , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Humanos , Polietilenoglicóis , Prostaglandinas A
13.
J Mater Chem B ; 10(25): 4771-4782, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35671131

RESUMO

Synergistic therapy, especially the combination of photothermal therapy and chemotherapy, has been proposed as an effective therapeutic approach for breast cancer treatment. In this study, a smart platform for synergistic photothermal therapy and chemotherapy was developed by hybridizing doxorubicin-encapsulated thermosensitive liposomes and gold nanorods into porous scaffolds of gelatin and polyglutamic acid (Dox-lipo/AuNR/Gel/PGA). The Dox-lipo/AuNR/Gel/PGA composite scaffolds had good photothermal conversion and temperature-dependent doxorubicin release properties. Under near-infrared laser irradiation, the composite scaffolds increased the local temperature to not only kill the breast cancer cells in the scaffolds but also accelerate the release of doxorubicin to eliminate the breast cancer cells surrounding the scaffolds. In vitro cell culture and in vivo mouse experiments demonstrated that the synergistic effects of photothermal ablation combined with doxorubicin-induced inhibition of the breast cancer cells in and surrounding the composite scaffolds under near-infrared laser irradiation. Moreover, after drug release was complete, the composite scaffolds fostered human bone marrow-derived mesenchymal stem cell proliferation. These results suggested that the composite scaffolds provided synergistic photothermal therapy and chemotherapy for breast cancer cell elimination at the early stage and promoted stem cell activities at the late stage. Therefore, this composite scaffold holds great potential as a synergistic therapy platform for breast cancer treatment.


Assuntos
Neoplasias da Mama , Lipossomos , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina , Feminino , Humanos , Camundongos , Terapia Fototérmica , Prostaglandinas A
14.
Pediatr Rheumatol Online J ; 20(1): 42, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710418

RESUMO

OBJECTIVE: The aim of this study was to analyze the usefulness of myeloid-related protein 8/14 (MRP8/14) in the prediction of disease course in a real-world setting for patients with new-onset juvenile idiopathic arthritis (JIA), to identify the relationship between MRP8/14 and disease activity using the physician's global assessment of disease activity (PGA), and determine whether the MRP8/14 levels measured in serum and plasma are equally useful. METHODS: In this prospective follow-up study, 87 new-onset non-systemic JIA patients were studied. Blood and synovial fluid samples were collected prior to any antirheumatic medication use. MRP8/14 was measured from serum (S-MRP8/14), plasma (P-MRP8/14), and synovial fluid samples using ELISA. RESULTS: The baseline MRP8/14 blood levels were significantly higher in patients using synthetic antirheumatic drugs than in patients with no systemic medications at 1 year after diagnosis in serum (mean 298 vs. 198 ng/ml, P < 0.001) and in plasma (mean 291 vs. 137 ng/ml, P = 0.001). MRP8/14 levels at the time of JIA diagnosis were higher in patients who started methotrexate during 1.5-year follow-up compared to those who achieved long-lasting inactive disease status without systemic medications (serum: mean 298 vs. 219 ng/ml, P = 0.006 and plasma: 296 vs. 141 ng/ml, P = 0.001). P-MRP8/14 was the most effective predictive variable for disease activity (by PGA) in linear multivariate regression model (combined to ESR, CRP, leukocytes, and neutrophils), whereas S-MRP8/14 was not significant. CONCLUSION: Blood MRP8/14 levels at baseline seem to predict disease course in new-onset JIA patients. P-MRP8/14 might be better than S-MRP8/14 when assessing disease activity at the time of JIA diagnosis.


Assuntos
Antirreumáticos , Artrite Juvenil , Antirreumáticos/uso terapêutico , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Biomarcadores , Calgranulina A , Calgranulina B , Seguimentos , Humanos , Estudos Prospectivos , Prostaglandinas A/uso terapêutico
15.
J AAPOS ; 26(3): 126.e1-126.e5, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35550862

RESUMO

PURPOSE: To examine the incidence of uveitis in children prescribed prostaglandin analogs (PGAs) for glaucoma. METHODS: In this dual-center cohort study, the medical records of consecutive patients <18 years old treated with a PGA between January 1, 2012, and December 31, 2018, were reviewed retrospectively. Patients with all forms of glaucoma, including those with a prior history of uveitis, were included. Patients who had been on a PGA prior to their first recorded visit were excluded. Patient charts were reviewed for new or recurrent uveitis during the first year of PGA therapy. RESULTS: A total of 103 children (147 eyes) were included, with a total PGA exposure of 1,352 child-months. Ninety-eight children (142 eyes) tolerated the PGA without an episode of uveitis. Five patients with a documented prior history of uveitis experienced a unilateral episode of uveitis. A review of their medical records identified prescribed or unscheduled decrease in topical steroids or immunosuppressive medication as the most likely cause of uveitis recurrence. CONCLUSIONS: This study provides further evidence that PGAs are unlikely to induce uveitis in children being treated for glaucoma and suggests that this may also be true in those with a history of uveitis. We are unable to evaluate whether PGAs make recurrence more likely or the tapering of steroids more difficult.


Assuntos
Glaucoma , Uveíte , Adolescente , Anti-Hipertensivos/uso terapêutico , Estudos de Coortes , Glaucoma/tratamento farmacológico , Glaucoma/etiologia , Humanos , Pressão Intraocular , Prostaglandinas A/uso terapêutico , Prostaglandinas Sintéticas/efeitos adversos , Estudos Retrospectivos , Esteroides , Uveíte/induzido quimicamente , Uveíte/diagnóstico , Uveíte/tratamento farmacológico
16.
J Mater Chem B ; 10(22): 4261-4273, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35583206

RESUMO

Micelles as nanocarriers not only offer new opportunities for early diagnosis and treatment of malignant cancers but also encounter numerous barriers in the path of efficient delivery of drugs to diseased areas in the body. To address these issues, we developed a pH/GSH responsive nano-prodrug micelle (NLG919/PGA-Cys-PPA@Gd) with a high drug-loading ratio and controlled drug release performance for MRI-guided tumor photodynamic therapy (PDT) and immune synergistic therapy. Under normal conditions, theranostic nanomicelles remained stable and in a photo-quenched state. Upon accumulation in the tumor site, however, the micelles demonstrated tumor microenvironment (TME) triggered photoactive formed-PPA (a photosensitizer) and NLG919 (an indoleamine 2,3-dioxygenase (IDO) inhibitor) release because the amide bonds of PGA-Cys-PPA and the disulfide linkage of Cys were sensitive to pH and GSH, respectively. More importantly, these micelles could avoid the undesired PPA leakage in blood circulation due to the conjugation between PPA and polymers. Furthermore, the obtained micelles could also enhance the contrast of T1-weighted MRI of tumors by virtue of their high relaxivity (r1 = 29.85 mM-1 s-1). In vitro and in vivo results illustrated that the micelles had good biocompatibility and biosafety. On the basis of the efficient drug delivery strategies in PDT and IDO pathway inhibition, this intelligent dual-drug delivery system could serve as an effective approach for MRI guided combination therapy of cancer.


Assuntos
Neoplasias , Fotoquimioterapia , Pró-Fármacos , Humanos , Imageamento por Ressonância Magnética , Micelas , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Pró-Fármacos/química , Prostaglandinas A , Triazenos , Microambiente Tumoral
17.
Carbohydr Polym ; 290: 119499, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35550777

RESUMO

As an important transcription factor, c-Jun could upregulate growth factors expression in Schwann cells (SCs). Arginine-Glycine-Aspartate (RGD)-functionalized chitosan-graft-polyethyleneimine (RCP) gene vectors were prepared through the maleic anhydride & the carbodiimide methods, and electrostatically bound with c-Jun plasmids (pJUN), finally loaded on poly-L-lactic acid/silk fibroin parallel fiber films to fabricate nerve scaffold (RCP/pJUN-PSPF@PGA), which could locally deliver c-Jun plasmids into SCs via the mediation of RGD peptides, and upregulate the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in SCs. After the scaffold was bridged in sciatic nerve defect, the delivery of c-Jun plasmids from RCP/pJUN-PSPF@PGA facilitated SCs to sustain the expressions of NGF, BDNF and vascular endothelial growth factor in the injury field, promoting myelination, axonal growth and microvascular generation and nerve regeneration, muscle reinnervation and functional recovery. These results suggested that RCP/pDNA-PSPF@PGA, as an effective gene delivery platform, could provide a local gene therapy to improve nerve regeneration.


Assuntos
Quitosana , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Quitosana/metabolismo , Terapia Genética , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Regeneração Nervosa , Oligopeptídeos , Polietilenoimina/metabolismo , Prostaglandinas A/metabolismo , Células de Schwann , Nervo Isquiático/lesões , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Urol Oncol ; 40(7): 343.e1-343.e6, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35537905

RESUMO

INTRODUCTION AND OBJECTIVE: Partial gland ablation (PGA) for localised prostate cancer (CaP) aims to eradicate clinically significant tumours while preserving healthy tissue, thereby decreasing the likelihood of side effects compared to whole-gland approaches. Although salvage radical prostatectomy (sRP) is a well-described salvage option in cases of PGA failure, the evidence supporting salvage PGA (sPGA) is limited. We hereby report the oncologic and functional outcomes of patients treated with sPGA following initial treatment with primary PGA (pPGA). METHODS: We describe the findings of a retrospective review of patients who had a CaP recurrence after pPGA and then underwent sPGA, at 3 medical centers in Ontario, Canada, between 2005 and 2017. Oncological outcomes following sPGA were assessed for biochemical recurrence (BCR) and biopsy-proven recurrence (BPR). Functional outcomes were described using the international prostate symptom score (IPSS), international index of erectile function (IIEF), and rates of urinary incontinence (use of >1 pad/day). RESULTS: We identified 25 patients who underwent sPGA following pPGA (hemiablation in 48% and zonal ablation in 52% of the patients). The median length of time was 16.8 months (interquartile range [IQR] 14.0-19.1) from pPGA to sPGA and 47.06 months (IQR 19.9-171.3) from pPGA to date of last follow up. High intensity focused ultrasound (HIFU) was the only modality used in all patients. At baseline, the median age was 65 years (IQR 52-77) and median prostate specific antigen (PSA) level was 7.46 ng/mL (IQR 1-25). The median time from pPGA to BPR was 12.7 months (IQR 5.19-36). At BPR following pPGA, 4 patients (17%) had CaP grade group (GG) 1, 10 patients (42%) had GG2, 6 patients (25%) had GG3, and 4 patients (17%) had GG4 disease, with a median PSA of 3.58 ng/mL (IQR 0.67-19). The median length of follow up after sPGA was 27.3 months (IQR 14.5-86.3). Following sPGA, 13/25 patients (52%) had BCR with median time to recurrence of 14 months (IQR 2.5-82.15), with a recurrence-free survival of 24.5 months (95% confidence interval: 15.3-not reached). Of those 13 patients, 4 were managed with sRP, 4 were managed with salvage radiotherapy, 3 were managed with androgen-deprivation therapy, 1 had a third PGA with HIFU, and 1 was managed with active surveillance. The mean change from baseline to last follow up in IPSS and IIEF scores was +1.3 (P = 0.66) and -2.3 (P = 0.32), respectively. Urinary incontinence was reported by 9% of patients at baseline, with only one additional patient developing incontinence following sPGA. CONCLUSION: Our present study demonstrates that after a median follow-up of 27 months, sPGA for recurrent CaP following pPGA provides disease control in up to 50% of patients with nonsignificant detrimental effects on functional outcomes. Appropriate patient selection and adequate staging are important to consider before offering PGA to patients.


Assuntos
Neoplasias da Próstata , Incontinência Urinária , Idoso , Antagonistas de Androgênios , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Ontário , Prostaglandinas A , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Terapia de Salvação , Resultado do Tratamento
19.
Curr Med Res Opin ; 38(7): 1189-1201, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35621005

RESUMO

OBJECTIVE: Analysis and comparison of country-level data from the VISIONARY study, examining treatment outcomes with the topical fixed-dose combination of preservative-free tafluprost (0.0015%) and timolol (0.5%) (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) who were insufficiently treated with or unable to tolerate either beta-blocker or prostaglandin analogue (PGA) topical monotherapy. METHODS: A European, prospective, observational study was conducted in 11 countries. Adults with OAG/OHT were switched to the PF tafluprost/timolol FC from either PGA or beta-blocker topical monotherapy. Statistical analysis examined changes in mean standard deviation (SD) intraocular pressure (IOP) from baseline at Week 4, Week 12 and Month 6. Data were documented for each eye separately at baseline and during follow up visits, with the eye reported to have the higher IOP (mmHg), as measured using Goldmann applanation tonometry, being selected for analysis (study eye). Country-level subanalysis examined outcomes by prior monotherapy, diagnosis and timing of dosing for those countries recruiting ≥20 patients (Country-level Subanalysis Population). Two-sided paired t-test was used to assess significance regarding mean IOP reduction from baseline and a compound symmetry covariance model was used in cross-country comparisons regarding variation in IOP change from baseline. Treatment-related adverse events (AEs) were evaluated. RESULTS: Mean (SD) age among patients recruited to the VISIONARY study ranged between 63.9 (11.8) and 72.4 (10.6) years across all countries. The majority of participants (>50%) were female in each country. The Country-level Subanalysis Population included 551 eyes. Mean (SD) IOP was significantly reduced from baseline in each country at Week 4, Week 12 and Month 6 (p < .0001). Mean IOP reduction at Month 6 ranged from 5.0 mmHg (22.6%, Hungary) to 7.8 mmHg (31.8%, Latvia) and varied significantly between countries (p < .001). The greatest reductions were in Latvia and Russia, where baseline IOP was highest. Country-level IOP reductions were significant irrespective of prior monotherapy, diagnosis or dosing time (p < .0001). Most treatment-related AEs occurred in the UK (26 events, 73% mild). One serious AE was reported (Russia, status asthmaticus). Tolerability with PF tafluprost/timolol FC therapy was rated as good/very good by most patients (85.7-100%) in all countries. CONCLUSION: Subanalysis of VISIONARY study data revealed significant IOP reductions following a switch to the PF tafluprost/timolol FC from either PGA or beta-blocker topical monotherapy. Cross-country variation was likely due to baseline IOP differences. Within country, outcomes were consistent regardless of diagnosis, dosing or prior monotherapy. Treatment was generally well tolerated.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Anti-Hipertensivos/efeitos adversos , Combinação de Medicamentos , Feminino , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/tratamento farmacológico , Conservantes Farmacêuticos/uso terapêutico , Estudos Prospectivos , Prostaglandinas A/uso terapêutico , Prostaglandinas F , Timolol/efeitos adversos , Resultado do Tratamento
20.
Mar Drugs ; 20(5)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35621967

RESUMO

Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria and causes inflammatory diseases. We searched MeOH extracts of collected marine organisms for inhibitors of LPS-induced nitric oxide (NO) production in RAW264.7 cells and identified prostaglandin A2 (PGA2) as an active compound from the MeOH extract of the soft coral Lobophytum sp. PGA2 inhibited the production of NO and reduced the expression of inducible NO synthase (iNOS) in LPS-stimulated RAW264.7 cells. Although short preincubation with PGA2 did not inhibit LPS-induced degradation and resynthesis of IκBα, the suppressive effect of PGA2 was observed only after a prolonged incubation period prior to LPS treatment. In addition, PGA2-inhibited NO production was negated by the addition of the EP4 antagonist L161982. Thus, PGA2 was identified as an inhibitor of LPS-induced inflammatory signaling in RAW264.7 cells.


Assuntos
Antozoários , Lipopolissacarídeos , Animais , Antozoários/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Prostaglandinas A/metabolismo , Prostaglandinas A/farmacologia
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