RESUMO
Enteric glial cells (EGCs) play an important role in visceral hypersensitivity associated with irritable bowel syndrome (IBS). Losartan (Los) is known to reduce pain; however, its function in IBS is unclear. The present study aimed to investigate Los's therapeutic effect on visceral hypersensitivity in IBS rats. Thirty rats were randomly divided into control, acetic acid enema (AA), AA + Los low, medium and high dose groups in vivo. EGCs were treated with lipopolysaccharide (LPS) and Los in vitro. The molecular mechanisms were explored by assessing the expression of EGC activation markers, pain mediators, inflammatory factors and angiotensin-converting enzyme 1(ACE1)/angiotensin II (Ang II)/Ang II type 1 (AT1) receptor axis molecules in colon tissue and EGCs. The results showed that the rats in the AA group showed significantly higher visceral hypersensitivity than the control rats, which was alleviated by different doses of Los. The expression of GFAP, S100ß, substance P (SP), calcitonin gene-related peptide (CGRP), transient receptor potential vanilloid 1 (TRPV1), tumor necrosis factor (TNF), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) was considerably increased in colonic tissues of AA group rats and LPS-treated EGCs compared with control rats and EGCs, and reduced by Los. In addition, Los reversed ACE1/Ang II/AT1 receptor axis upregulation in AA colon tissues and LPS-treated EGCs. These results show that Los inhibits ACE1/Ang II/AT1 receptor axis upregulation by suppressing EGC activation, resulting in reduced expression of pain mediators and inflammatory factors, thereby alleviating visceral hypersensitivity.
Assuntos
Síndrome do Intestino Irritável , Losartan , Animais , Ratos , Ácido Acético/toxicidade , Enema , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Losartan/farmacologia , Losartan/uso terapêutico , Neuroglia , Dor/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Peptidil Dipeptidase A/metabolismoRESUMO
The use of superoxide dismutase (SOD) is currently limited by its short half-life, rapid plasma clearance rate, and instability. We synthesized a small library of biofriendly amphiphilic polymers that comprise methoxy poly(ethylene glycol)-poly(cyclohexane-1,4-diyl acetone dimethyleneketal) (mPEG-PCADK) and mPEG-poly((cyclohexane86.7%, 1,5-pentanediol13.3%)-1,4-diyl acetone dimethylene ketal) (PK3) for the targeted delivery of SOD. The novel polymers could self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, long circulation time, and inflammation-targeting effects. These materials generated a better pH-response curve and exhibited better hydrolytic kinetic behavior than PCADK and PK3. The polymers showed good biocompatibility with protein drugs and did not induce an acidic microenvironment during degradation in contrast to materials such as PEG-block-poly(lactic-co-glycolic acid) (PLGA) and PLGA. The SOD that contained reverse micelles based on mPEG2000-PCADK exhibited good circulation and inflammation-targeting properties. Pharmacodynamic results indicated exceptional antioxidant and anti-inflammatory activities in a rat adjuvant-induced arthritis model and a rat peritonitis model. These results suggest that these copolymers are ideal protein carriers for targeting inflammation treatment.
Assuntos
Portadores de Fármacos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Superóxido Dismutase-1/química , Animais , Artrite Experimental/tratamento farmacológico , Concentração de Íons de Hidrogênio , Hidrólise , Inflamação/metabolismo , Cinética , Teste de Materiais , Peritonite/tratamento farmacológico , Ratos , Superóxido Dismutase-1/uso terapêuticoRESUMO
INTRODUCTION: Psychological health is important to old patients with benign prostatic hyperplasia (BPH) after prostatic surgery. In this retrospective cohort study, we evaluated the effect of personalized preoperative education in the reduction of perioperative anxiety in old BPH patients after prostatic surgery. METHODS: Senior patients (≥65 years) admitted with a diagnosis of BPH and scheduled for initial transurethral resection of the prostate from January 1, 2017 to November 30, 2019 were retrieved. Patients in the preoperatively educated group completed the Chinese version of generalized anxiety disorder 7-item scale (GAD-7) form to evaluate their anxiety level at admission and 14 days clinical visits after individual preoperative education. Patients in the control group completed GAD-7 forms but did not receive personalized preoperative education. Patients in both groups discussed their disease with physicians during clinic visits and after admission, and were given an informed consent about their treatment plans. RESULTS: Seven hundred and twenty-four patients were retrieved, including 312 patients who received preoperative education and 412 patients who did not. There were significantly lower postoperative GAD-7 score and fewer moderate to severe postoperative anxiety patients in the preoperatively educated group (p < 0.01). Patients with education above secondary education level had less perioperative anxiety. CONCLUSION: Personalized education incorporated with shared valuable physiological and psychological experience and expectations dealing with BPH, in comparison to traditional uniformed patient education and informed consent before surgery, may reduce perioperative anxiety more efficiently in BPH patients. A higher educational level helps patients reduce perioperative anxiety before and after their personalized preoperative education.
Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Ansiedade/prevenção & controle , Transtornos de Ansiedade , Humanos , Masculino , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Estudos RetrospectivosRESUMO
HYPOTHESIS: Invoking cooperative assembly of the uracil-functionalized supramolecular polymer BU-PPG [uracil end-capped poly(propylene glycol)] upon association with the nucleobase adenine derivative A-MA [methyl 3-(6-amino-9H-purin-9-yl)propanoate] as a model drug provides a new concept to control and tune the properties of supramolecular complexes and holds significant potential for the development of safer, more effective drug delivery systems. EXPERIMENTS: BU-PPG and A-MA were successfully developed and exhibited specific recognition and high affinity, which enabled reversible complementary adenine-uracil (A-U) hydrogen bonding-induced formation of spherical micelles in aqueous solution. The self-assembly and controllable A-MA release behavior of BU-PPG/A-MA micelles were studied using morphological analysis and optical and light scattering techniques to investigate the effect of photoirradiation and temperature on the complementary hydrogen bond interactions between BU-PPG and A-MA. FINDINGS: The resulting micelles possess unusual physical properties, including controlled photoreactivity kinetics, controllable self-assembled morphology and low cytotoxicity in vitro, as well as reversible temperature-responsive behavior. Importantly, irradiated micelles exhibited excellent long-term structural stability under normal physiological conditions and serum disturbance. Increasing the temperature triggered rapid release of A-MA by disrupting A-U complexes. These findings represent an entirely new, promising strategy for the development of multi-controlled release drug delivery nanocarriers based on complementary hydrogen bonding interactions.
Assuntos
Adenina/química , Preparações de Ação Retardada/química , Raios Ultravioleta , Uracila/química , Adenina/análogos & derivados , Adenina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Células HeLa , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Micelas , Nanopartículas/química , Polímeros/síntese química , Polímeros/química , Polímeros/farmacologia , Temperatura , Uracila/farmacologiaRESUMO
A new biflavonoid, paucinervin K (1) and a new triterpene, 23-hydroxy-friedelin (2), together with eleven known compounds 3-13 were isolated from the leaves of Garcinia paucinervis. Their structures, including stereochemistry, were determined by spectroscopic analysis of NMR, MS, IR and ECD calculation and the octant rule. Some of the isolated compounds were tested for antiproliferative, α-glucosidase inhibitory and antioxidant activities in vitro. Compounds 1, 3, 4, 5 and 9 showed moderate preferential antioxidant and hypoglycemic activities. Compounds 3-6 and 9 exhibited potent growth inhibition against HepG-2 and PC-3 cell lines with IC50 values ranging from 1.02-10.05 µM.
Assuntos
Antioxidantes/farmacologia , Garcinia/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/química , Antioxidantes/isolamento & purificação , Biflavonoides/química , Biflavonoides/isolamento & purificação , Biflavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Células Hep G2 , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Estrutura Molecular , Neoplasias/tratamento farmacológico , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , alfa-Glucosidases/metabolismoRESUMO
Three new xanthones, paucinervins H-J (1-3), as well as eleven known compounds (4-14), were isolated from the leaves of Garcinia paucinervis. The structures of the new compounds (1-3) were elucidated by 1D, 2D NMR spectra and HR ESIMS. In vitro antiproliferative activity against human promyelocytic leukemia HL-60 cells was tested, among which, compounds 2, 5, 6 and 7 exhibited strong growth inhibitory effects with GI50 values ranging from 1.30 to 9.08 µM, respectively. Preliminary SARs were also discussed.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Garcinia/química , Leucemia Promielocítica Aguda/tratamento farmacológico , Extratos Vegetais/farmacologia , Xantonas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Relação Dose-Resposta a Droga , Células HL-60 , Humanos , Concentração Inibidora 50 , Leucemia Promielocítica Aguda/metabolismo , Estrutura Molecular , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Relação Estrutura-Atividade , Xantonas/química , Xantonas/isolamento & purificaçãoRESUMO
Three new prenylated xanthones, garcinexanthones G-I (1-3), together with fifteen known ones (4-18) were identified from the leaves of Garcinia lancilimba. Their structures were determined by extensive spectroscopic analyses. Most of the compounds exhibited inhibitory effects against HL-60 (human leukemia), A549 (human lung cancer), and MCF-7 (human breast cancer) cell lines. Among them, compounds 7, 17, and 13 exhibited the most pronounced growth inhibitory activity against HL-60, A549, and MCF-7 cell lines with GI50 values of 1.68, 4.88, and 6.28 µM, respectively.
Assuntos
Garcinia/química , Xantonas/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Células HL-60 , Humanos , Leucemia/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Células MCF-7 , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Prenilação , Xantonas/química , Xantonas/farmacologia , Xantonas/uso terapêuticoRESUMO
Four quinolone alkaloids (1-4) and three indole alkaloids (20-22), together with 30 known alkaloids (5-19, 23-37), were isolated from the fruits of Euodia rutaecarpa. Their structures were established by spectroscopic analyses. The in vitro cytotoxic activities of these alkaloids against leukaemia HL-60 and prostate cancer PC-3 cell lines were evaluated.