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1.
Signal Transduct Target Ther ; 6(1): 405, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795208

RESUMO

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

2.
BMC Ophthalmol ; 21(1): 332, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34511057

RESUMO

BACKGROUND: The present study sought to observe the effect of retaining intact posterior capsule in congenital cataract surgery in children aged 4-8 years. METHODS: This is a retrospective case control study. Seventy-seven children (130 eyes) aged from 4 to 8 years who underwent cataract surgery were divided into two groups. In Group A, 50 eyes underwent phacoemulsification, intraocular lens implantation and posterior capsule capsulotomy combined with anterior vitrectomy. In Group B, 80 eyes underwent cataract phacoemulsification and intraocular lens implantation. The postoperative visual acuity and the rate of complications were compared. RESULTS: In all patients, cataract surgeries were performed evenly without intraoperative complications. The follow-up time ranged from 6 months to 42 months. No apparent visual axis opacity was detected in group A during the follow-up. By the last visit, apparent visual axis opacity was detected in 31 eyes (38.75%) in group B. Among them, 9 eyes (29.03%) with mild posterior capsule opacification (PCO) were treated with Nd:YAG laser, 3 eyes (9.68%) with thick proliferative membranes were treated with posterior capsule capsulotomy combined with anterior vitrectomy and proliferative membranes in 19 eyes (61.29%) were completely aspired and the posterior capsule was retained. During follow-up, only 2 (6.45%) eyes had PCO recurrence and were treated with Nd:YAG laser. The visual acuity was significantly higher than that before surgery in all patients. CONCLUSIONS: For older children, the incidence of PCO will be low even if intact posterior capsule is retained. Either Nd:YAG laser or surgical treatment for PCO will be able to maintain good vision.


Assuntos
Opacificação da Cápsula , Catarata , Cápsula do Cristalino , Lentes Intraoculares , Facoemulsificação , Adolescente , Opacificação da Cápsula/cirurgia , Estudos de Casos e Controles , Criança , Humanos , Cápsula do Cristalino/cirurgia , Implante de Lente Intraocular , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
3.
Front Pharmacol ; 12: 724515, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421617

RESUMO

Sepsis is defined as a life-threatening organ dysfunction syndrome with high morbidity and mortality caused by bacterial infection. The major characteristics of sepsis are systemic inflammatory responses accompanied with elevated oxidative stress, leading to multiple organ dysfunction syndrome (MODS), and disseminated intravascular coagulation (DIC). As a molecular chaperon to repair unfolded proteins, heat shock protein 70 (HSP70) maintains cellular homeostasis and shows protective effects on inflammatory damage. HSP 90 inhibitors were reported to exert anti-inflammatory effects via activation of the heat shock factor-1 (HSF-1), leading to induction of HSP70. We evaluated the beneficial effect of HSP 90 inhibitor NVP-AUY 922 (NVP) on multiple organ dysfunction syndrome induced by lipopolysaccharide (LPS) and further explored the underlying mechanism. NVP (5 mg/kg, i.p.) was administered 20 h prior to LPS initiation (LPS 30 mg/kg, i.v. infusion for 4 h) in male Wistar rats. Results demonstrated that pretreatment with NVP significantly increased survival rate and prevented hypotension at 6 h after LPS injection. Plasma levels of ALT, CRE and LDH as well as IL-1ß and TNF-α were significantly reduced by NVP at 6 h after LPS challenge. The induction of inducible NO synthase in the liver, lung and heart and NF-κB p-p65 and caspase 3 protein expression in the heart were also attenuated by NVP. In addition, NVP markedly induced HSP70 and HO-1 proteins in the liver, lung and heart after LPS injection. These results indicated that NVP possessed the anti-inflammatory and antioxidant effects on LPS-induced acute inflammation, which might be associated with HSP70 and HO-1, leading to prevent MODS in sepsis. NVP might be considered as a novel therapeutic strategy in the prevention of sepsis-induced MODS.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34357418

RESUMO

PURPOSE: To study the association of myopia progression with the morphological changes of optic disc and ß-peripapillary atrophy (ß-PPA) in 8-11 years old primary school students. METHODS: This study was a prospective, school-based investigation. This study included 610 children (1008 eyes) who were continuously observed and had data available from 2016 to 2017 in the Sanhe Cohort Study of the Risk Factors for Myopia (SCSRFM). The children underwent a comprehensive eye examination including measurement of visual acuity, autorefractometry, and posterior segment of the eye. ß-PPA regions and optic disc ovality index were identified and measured on the fundus photographs. RESULTS: The prevalence of myopia was 72.62% (732/1008) in 2016. In myopic children, the prevalence of the vertical ß-PPA, the horizontal ß-PPA, and the oval optic disc were 75.68% (554/732), 75.96% (556/732) and, 11.61% (85/732) respectively. From 2016 to 2017, with the progression of vertical ß-PPA, horizontal ß-PPA, area of ß-PPA, and optic disc ovality index, the myopic diopter and the axial length (AL) were increased. The progression of horizontal ß-PPA was significantly correlated with the progression of myopic diopter and AL (all p < 0.05). The analysis on the distribution of progression rate of parameters in different groups found that the progression rate of horizontal ß-PPA, area of ß-PPA, and optic disc ovality index increased with the increase of the progression of diopter and AL. The progression of horizontal ß-PPA, area of ß-PPA, optic disc ovality index, and diopter in girls were greater than that in boys, and the progression of optic disc ovality index and diopter had a statistical significance (all p < 0.05). CONCLUSIONS: The 1-year follow-up study of the third-grade primary school students showed that with the progression of myopia and the growth of AL, ß-PPA and optic disc ovality index also changed. There was a positive correlation between the change of ß-PPA and optic disc ovality index and the progression of myopia diopter and AL.

5.
Int J Hyperthermia ; 38(1): 862-874, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34078225

RESUMO

Objective: Heat stroke (HS) elicits the systemic inflammatory responses that result in multiple organ dysfunction (MOD). Heat shock response and autophagy are activated during heat stress for removal of damaged organelles and proteins, emerging as a major regulator of cellular homeostasis. Ethyl pyruvate (EP) is a derivative of pyruvic acid and possesses antioxidant and anti-inflammatory effects. This study aims to investigate the effects of EP on MOD in HS rats and explore the possible mechanisms.Method: Anesthetized rats were placed in a heating chamber (42 °C) to elevate the core body temperature attaining to 42.9 °C. Rats were then moved to room temperature and monitored for 6 h. EP (60 mg/kg, i.v.) was administered 30 min prior to heat exposure.Results: Results showed that EP significantly reduced HS-induced increases in plasma levels of LDH, CPK, GPT and CK-MB, reversed the decrease of platelet counts, and alleviated intestinal mucosal and pulmonary damage. Moreover, EP reduced pro-inflammatory protein, including TNF-α, IL-6, IL-1ß, HMGB1 and iNOS, and induced stress proteins, heme oxygenase-1 (HO-1), heat shock protein (HSP) 70 and HSP90 in the liver of HS rats. The levels of HS-activated autophagy-regulatory proteins were affected by EP, in which the phosphorylated mTOR and AKT were reduced, and the phosphorylated AMPK increased, accompanied with upregulation in ULK1, Atg7, Atg12 and LC3II, and downregulation of p62.Conclusion: In conclusion, EP ameliorated HS-induced inflammatory responses and MOD, and the underlying mechanism is associated with the induction of the stress proteins HO-1 and HSP70 as well as restorage of autophagy.


Assuntos
Golpe de Calor , Proteínas de Choque Térmico , Animais , Autofagia , Golpe de Calor/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/etiologia , Piruvatos , Ratos
6.
Int J Clin Pract ; 75(8): e14272, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33908134

RESUMO

PURPOSE: To observe the effect of phacoemulsification and intraocular lens (IOL) implantation with or without lens capsular tension ring (CTR) on retinitis pigmentosa (RP) combined with cataract patients. DESIGN: Retrospective cases series study. METHODS: Sixty-three cases (84 eyes) of RP with cataract were collected, including 30 males and 33 females. Phacoemulsification with 3.0 mm clear corneal incision was performed in all the patients. IOL and CTR implantation were performed in 44 eyes, and IOL implantation alone was performed in 40 eyes. All cases were followed up at 1 day, 1 week and 1, 3, 6,12 months after the surgery to compare the best-corrected visual acuity (BCVA), intraocular pressure (IOP), corneal endothelial cell count (ECC) and complications before and after the surgery. RESULTS: All surgery were successfully completed by the same physician, and IOL and CTR were all implanted in capsule without complications. The BCVA at 6 months after surgery was 0.91 ± 0.88 LogMAR, showing an improvement compared with the BCVA(1.3 ± 0.7LogMAR) before surgery and there was a statistically significant difference (P = .003). Four cases of capsule contraction syndrome (CCS) occurred in no CTR implantation group and there was no CCS in CTR group. There was a statistically significant difference in the incidence of CCS between two groups (P = .047). CONCLUSIONS: Phacoemulsification for RP combined with cataract is safe and reliable, and CTR implantation is conducive to reducing the complications caused by capsule contraction.


Assuntos
Catarata , Cápsula do Cristalino , Retinite Pigmentosa , Catarata/complicações , Feminino , Humanos , Cápsula do Cristalino/cirurgia , Implante de Lente Intraocular , Masculino , Complicações Pós-Operatórias/prevenção & controle , Retinite Pigmentosa/complicações , Estudos Retrospectivos
7.
Curr Eye Res ; 46(9): 1406-1413, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33645355

RESUMO

Purpose: To investigate the prevalence and clinical characteristics of myelinated retinal nerve fibre (MRNF) in a large teleophthalmology system.Methods: All records between January 2015 and December 2015 from Daheng Prust teleophthalmology system were reviewed by 2 ophthalmologists independently. MRNF was classified into continuous group and discontinuous group according to the relationship between MRNF patches and optic disc. The number, total area and location of MRNF patches were analysed. Concomitant ocular diseases were documented.Results: Out of 51469 subjects, MRNF was detected in 304 eyes of 263 subjects with a prevalence rate of 0.51 ± 7.1% per subject and 0.30 ± 5.4% per eye. Among 304 eyes with MRNF, 239 (78.6%) eyes were in continuous group and 65 (21.4%) eyes were in discontinuous group. Single MRNF patch was found in 249 (81.9%) eyes and multiple MRNF patches were found in 55 (18.1%) eyes. MRNF of small size was found in 150 (49.3%) eyes. The ratios of multiple MRNF patches and small-sized MRNF in the continuous group were significantly higher than those in the discontinuous group (P = .014 and P < .001). In continuous group, the MRNF patches were located most frequently in the superior region (68.6%) of the optic disc; In discontinuous group, the MRNF patches were located most frequently in the inferotemporal region (38.5%) of the retina. Epiretinal membrane (12 eyes, 3.9%) was the most common concomitant ocular disease.Conclusion: MRNF is uncommon in China. MRNF usually presents unilaterally and as a single small whitish patch that is connected with optic disc.

8.
Appl Psychol Meas ; 44(3): 182-196, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32341606

RESUMO

When computerized adaptive testing (CAT) is under stringent item exposure control, the precision of trait estimation will substantially decrease. A new item selection method, the dynamic Stratification method based on Dominance Curves (SDC), which is aimed at improving trait estimation, is proposed to mitigate this problem. The objective function of the SDC in item selection is to maximize the sum of test information for all examinees rather than maximizing item information for individual examinees at a single-item administration, as in conventional CAT. To achieve this objective, the SDC uses dominance curves to stratify an item pool into strata with the number being equal to the test length to precisely and accurately increase the quality of the administered items as the test progresses, reducing the likelihood that a high-discrimination item will be administered to an examinee whose ability is not close to the item difficulty. Furthermore, the SDC incorporates a dynamic process for on-the-fly item-stratum adjustment to optimize the use of quality items. Simulation studies were conducted to investigate the performance of the SDC in CAT under item exposure control at different levels of severity. According to the results, the SDC can efficiently improve trait estimation in CAT through greater precision and more accurate trait estimation than those generated by other methods (e.g., the maximum Fisher information method) in most conditions.

9.
J Biomed Sci ; 26(1): 62, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31470850

RESUMO

BACKGROUND: Loss of ovarian function, as in menopause or after ovariectomy (OVX), is closely associated with obesity and white adipose tissue (WAT) inflammation. Estrogen replacement protects against postmenopausal obesity but increases the risks of carcinogenesis. In the present study, we investigated the effects of long-term treatment of raloxifene (RAL), a selective estrogen receptor modulator, on the features of estrogen deficiency-induced obesity and explored the involvement of canonical and non-canonical Wnt regulation in vivo and in vitro. METHODS: Adult female rats received bilateral OVX and divided into 5 groups: (1) Sham, (2) OVX, (3) OVX + E2: OVX rats were administered with E2 (50 µg/kg, s.c., 3 times/week), (4) OVX + RAL: OVX rats were treated with RAL (gavage, 1 mg/kg/day) suspended in 0.8% carboxymethylcellulose (CMC), (5) OVX + CMC: 0.8% CMC as vehicle control. All treatments were given for 8 weeks beginning at 1 week after OVX. In 3 T3-L1 cells, the effects of RAL on adipogenesis and lipopolysaccharide (LPS)-induced inflammation were evaluated. RESULTS: Treatment with RAL significantly decreased body weight, visceral fat pad mass, adipocyte size and plasma levels of glucose but increased plasma adiponectin. RAL reduced the elevation of HIF-1α, VEGF-A and proinflammatory cytokines (MCP-1 and TNF-α) expression by inhibition of NF-κB p65 and JNK cascades in retroperitoneal WAT. This anti-inflammatory capacity of RAL may result from upregulation of secreted frizzle-related protein 5 (SFRP5), an adipokine that repressed Wnt5a signaling. Furthermore, RAL inhibited adipogenic factors such as PPAR-γ, C/EBP-α, and FABP4, and preserved canonical Wnt10b/ß-catenin protein expression. In 3 T3-L1 adipocytes, RAL (20 µM) diminished lipid accumulation and inhibited adipogenic factors accompanied with the induction of ß-catenin, which were effectively reversed by the ß-catenin inhibitor IWR-1-endo. In addition, RAL reduced LPS-induced NF-κB p65 and p-IκB expression as well as TNF-α secretion. Suppression of SFRP5 by small interfering RNA significantly abrogated the anti-inflammatory effects of RAL. CONCLUSIONS: Distinct activation of canonical ß-catenin on inhibition of adipogenesis and non-canonical SFRP5 on suppression of WAT inflammation may contribute to the beneficial effects of RAL. Therefore, this study provides a rationale for the therapeutic potential of RAL for postmenopausal obesity.


Assuntos
Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Inflamação/induzido quimicamente , Cloridrato de Raloxifeno/farmacologia , Receptores de Estrogênio/antagonistas & inibidores , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Proteínas Wnt/genética , Células 3T3-L1 , Tecido Adiposo/imunologia , Animais , Feminino , Regulação da Expressão Gênica , Lipopolissacarídeos/farmacologia , Camundongos , Ovariectomia , Ratos , Ratos Wistar , Proteínas Wnt/metabolismo , Proteína Wnt1
10.
Life Sci ; 232: 116672, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31336120

RESUMO

AIMS: Obesity is not only associated with metabolic diseases but is also a symptom of menopause in women. To date, there are no effective drugs for the management of obesity, and it is important to find new agents with fewer side effects, for the treatment of obesity. This study aimed to determine the anti-obesity effect of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, and its underlying mechanism in rats with ovariectomy-induced obesity. MAIN METHODS: Ovariectomy (Ovx) rats were treated with 17-DMAG (1 mg kg-1, intraperitoneally) for eight weeks from one week after surgery. The body weight, food intake, locomotor activity, adipogenic- and autophagy-related protein expression in white adipose tissue (WAT) and plasma triglyceride (TG) levels were measured in sham and Ovx rats. KEY FINDINGS: Compared with sham rats, Ovx rats showed increased weight gain, food intake, WAT mass, TG levels, adipogenic protein expression, and decreased locomotor activity. Furthermore, autophagy-related proteins and Foxo3a of WAT were significantly increased in Ovx rats. However, with the exclusion of increased food intake, the changes induced by Ovx were all reversed in 17-DMAG-treated Ovx rats. In addition, the expression of Hsp70 and phosphorylation of Akt increased in 17-DMAG-treated Ovx rats. SIGNIFICANCE: These results suggest that 17-DMAG significantly ameliorated obesity induced by Ovx, and this phenomenon is accompanied by the downregulation of adipogenic-related and autophagy-related proteins as well as the upregulation of Akt-phosphorylation and Hsp70 expression. Therefore, 17-DMAG may be a potential agent for preventing or treating obesity in postmenopausal women.


Assuntos
Benzoquinonas/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Lactamas Macrocíclicas/farmacologia , Obesidade/etiologia , Obesidade/prevenção & controle , Ovariectomia/efeitos adversos , Adipogenia , Tecido Adiposo/metabolismo , Animais , Autofagia , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Proteínas de Choque Térmico HSP90/metabolismo , Locomoção/efeitos dos fármacos , Ratos
11.
J Nutr Biochem ; 67: 111-122, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30884354

RESUMO

Estrogen deficiency in postmenopausal women is linked to the higher prevalence of obesity, type 2 diabetes and metabolic syndromes. Development of beige adipocytes (browning of WAT) increases energy expenditure and could be a promising strategy for obesity management. This study aimed to investigate the effects of phytoestrogen genistein (GEN) on white adipose tissue (WAT) inflammation, browning and hepatic lipogenesis in ovariectomized rats with high-fat diet (HFD) and further explore the underlying mechanism. Female Wistar rats received ovariectomy (Ovx) and HFD (45% fat) and then were administered with 17ß-estradiol (E2, 3 times/week, subcutaneously) or GEN (15 mg/kg or 30 mg/kg, gavage, once daily) for 4 weeks. Administration of GEN decreased Ovx-induced body weight gain and adiposity and improved insulin sensitivity as well as increased insulin signaling p-IRS1 and p-AKT in retroperitoneal WAT. Adipocyte hypertrophy and production of proinflammatory cytokines MCP-1, TNF-α and IL-6 were reduced by GEN. It also suppressed the activation of NF-κB pathway evidenced by attenuation of p65 and phospho-IκB levels. Additionally, GEN elevated myokine irisin and promoted WAT browning by increasing UCP-1, PRDM-16, PGC-1α and CIDEA proteins and Ppargc1a, Ucp-1 and Tbx-1 mRNA in inguinal WAT which is associated with up-regulation of nuclear estrogen receptor-α. Plasma levels of triglyceride and cholesterol were reduced by GEN treatment accompanied with inhibition of lipogenic proteins (p-ACC, SREBP-1, FAS and CD36) in the liver. Long-term treatment with GEN attenuated estrogen-deficiency-induced obesity, WAT inflammation and hepatic lipogenesis and promoted the induction of WAT browning. It may provide a promising approach to prevent obesity during menopause.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Genisteína/farmacologia , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/patologia , Adiponectina/sangue , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Fibronectinas/sangue , Insulina/sangue , Fígado/metabolismo , Ovariectomia , Paniculite/tratamento farmacológico , Paniculite/etiologia , Ratos Wistar , Proteína Desacopladora 1/metabolismo
12.
J Biomater Appl ; 32(6): 800-812, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29137495

RESUMO

Due to limited self-healing capacity in cartilages, there is a rising demand for an innovative therapy that promotes chondrocyte proliferation while maintaining its biofunctionality for transplantation. Chondrocyte transplantation has received notable attention; however, the tendencies of cell de-differentiation and de-activation of biofunctionality have been major hurdles in its development, delaying this therapy from reaching the clinic. We believe it is due to the non-stimulative environment in the injured cartilage, which is unable to provide sustainable physical and biological supports to the newly grafted chondrocytes. Therefore, we evaluated whether providing an appropriate matrix to the transplanted chondrocytes could manipulate cell fate and recovery outcomes. Here, we proposed the development of electrosprayed nanoparticles composed of cartilage specific proteins, namely collagen type II and hyaluronic acid, for implantation with pre-seeded chondrocytes into articular cartilage defects. The fabricated nanoparticles were pre-cultured with chondrocytes before implantation into injured articular cartilage. The study revealed a significant potential for nanoparticles to support pre-seeded chondrocytes in cartilage repair, serving as a protein delivery system while improving the survival and biofunctionality of transplanted chondrocytes for prolonged period of time.


Assuntos
Cartilagem Articular , Condrócitos , Nanopartículas , Tecidos Suporte , Animais , Materiais Biocompatíveis/química , Colágeno Tipo II/química , Masculino , Nanopartículas/química , Coelhos , Tecidos Suporte/química
13.
J Cancer ; 8(4): 617-625, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28367241

RESUMO

Background: MicroRNAs (miRNAs) are a class of endogenous, small non-coding RNAs which function as essential posttranscriptional modulators of gene expression tightly involved in a wide range of diseases, including the hepatocellular carcinoma (HCC). Here, the present study was designed to investigate the expression levels and cellular roles of miR-200a in HCC. Methods: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-200a in serums and cell lines. Bioinformation analysis, the luciferase reporter assay, qRT-PCR and western blotting were employed to validate Foxa2 as a direct target gene of miR-200a. Cell proliferation, migration and invasion were assessed to identify whether miR-200a could regulate the biological behaviors of HCC cells by targeting Foxa2. Results: In this study, a low level of miR-200a was observed in patients' serums and HCC cell lines. Overexpression of miR-200a in HCC cell lines reduced cell proliferation, migration and invasion. In addition, transcription factor forkhead box A2 (Foxa2) was identified as a novel target of miR-200a and downregulated at mRNA and protein levels in miR-200a overexpressed cells. Meanwhile, restoration of Foxa2 significantly reversed the tumor suppressive effects of miR-200a. Conclusions: These findings indicate that miR-200a regulates the proliferation, migration and invasion of HCC cells by targeting Foxa2, suggesting that miR-200a may function as a potential therapeutic molecular for the diagnosis and treatment of the liver cancer.

14.
Atherosclerosis ; 261: 105-110, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28242046

RESUMO

BACKGROUND AND AIMS: Leukocyte mitochondrial DNA (mtDNA) content reflects the oxidant-induced cell damage, which has been observed in a wide range of cardiovascular diseases. However, whether it correlates with coronary heart disease (CHD), which closely relates to oxidative stress, has never been elucidated before. The aim of this study was to explore association between mtDNA content and the presence and severity of CHD. METHODS: The study population consisted of 400 individuals (290 with CHD and 110 controls). A quantitative real-time PCR was performed to measure the relative content of mtDNA in peripheral blood cells (PBCs). Gensini score was used to evaluate the severity of coronary stenotic lesions. An unconditional multivariate logistic regression was developed to estimate the association between CHD risk and mtDNA content by using odds ratio (OR). This study is registered with ClinicalTrials.gov, number NCT02500823. RESULTS: CHD patients, compared to controls, had lower mtDNA content (median, 0.78 vs. 0.83, p < 0.001), and mtDNA levels significantly decreased following an increasing Gensini score (p < 0.001). By using the first (highest mtDNA content) quartile of mtDNA content of controls as reference, the adjusted ORs (95% CIs) for individuals in the second, third and highest quartile of mtDNA content were 1.78 (95% CI, 1.15-3.51), 2.21 (95% CI, 1.65-3.74) and 4.83 (95% CI, 2.67-8.64), respectively (p for trend <0.001). CONCLUSIONS: These preliminary results suggest that expression of mtDNA may be associated with atherogenesis. The level of peripheral blood mtDNA in predicting the severity of coronary atherosclerosis may have a relatively certain value.


Assuntos
Doença da Artéria Coronariana/genética , Estenose Coronária/genética , DNA Mitocondrial/sangue , Leucócitos/química , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Estenose Coronária/sangue , Estenose Coronária/diagnóstico , Estenose Coronária/epidemiologia , Feminino , Marcadores Genéticos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Índice de Gravidade de Doença
15.
Menopause ; 24(8): 959-969, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28350760

RESUMO

OBJECTIVE: Accumulating evidence demonstrates that raloxifene, a selective estrogen receptor modulator, possesses anti-inflammatory action. This study evaluates the preventive effects of long-term treatment of raloxifene on acute inflammation and multiple organ dysfunction syndrome (MODS) in ovariectomized (OVX) rats with endotoxemia and its underlying mechanism of action. METHODS: Adult female rats were OVX bilaterally to induce estrogen insufficiency. OVX rats were administered with raloxifene (1 mg/kg, gavage, once daily) for 8 weeks, beginning 1 week after surgery, followed by induction of sepsis via intravenous infusion of lipopolysaccharides (LPS; 30 mg/kg) for 4 hours. LPS-activated RAW 264.7 cells were used to investigate the mechanism of raloxifene. RESULTS: Ovariectomy amplified the endotoxemia-induced hypotensive effect, MODS, and superoxide anion production in the myocardium. The levels of inducible nitric oxide synthase, high mobility group box 1, and nuclear factor-κB p65 protein increased in OVX rats 6 hours after LPS initiation. Raloxifene mitigated MODS, together with reduced inducible nitric oxide synthase induction and fewer superoxide anions in organs. Raloxifene induced high levels of heat shock protein 70 (HSP70) and heme oxygenase 1 (HO-1), which are associated with an increase in the transcription factor heat shock factor-1 and Nrf-2, respectively. Pretreatment with quercetin, an inhibitor of HSP70, or SnPP, an inhibitor of HO-1, reversed the protective effects of raloxifene in septic OVX rats and LPS-activated macrophages. CONCLUSIONS: Long-term treatment with raloxifene reduces the severity of sepsis in OVX rats, attributed from up-regulation of HSP70 and HO-1 to exert the antioxidant and anti-inflammatory capacities. These findings provide new insights into bacterial infection during menopause and the molecular mechanism of raloxifene.


Assuntos
Endotoxemia/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Ovariectomia , Cloridrato de Raloxifeno/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Administração Oral , Animais , Modelos Animais de Doenças , Endotoxemia/metabolismo , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Heme Oxigenase-1/metabolismo , Insuficiência de Múltiplos Órgãos/metabolismo , Cloridrato de Raloxifeno/administração & dosagem , Ratos , Ratos Wistar , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem
16.
Mol Med Rep ; 14(6): 5155-5163, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27840979

RESUMO

Bacillus amyloliquefaciens JN68, which has been discussed with regards to its antimicrobial activities, was successfully isolated from healthy chicken intestines in the present study. Using the spot-on-the-lawn antagonism method, the preliminary study indicated that a suspension culture of the B. amyloliquefaciens JN68 strain can inhibit the growth of Aspergillus niger and Penicillium pinophilum. Furthermore, the cyclic lipopeptides (CLPs) produced by the B. amyloliquefaciens JN68 strain were further purified through acid precipitation and Bond Elut®C18 chromatography, and their structures were identified using the liquid chromatography­electrospray ionization­mass spectrometry (MS)/MS method. Purified CLPs exerted broad spectrum antimicrobial activities on various pathogenic and foodborne bacteria and fungi, as determined using the agar well diffusion method. Listeria monocytogenes can induce listeriosis, which is associated with a high mortality rate. Methicillin­resistant Staphylococcus aureus (MRSA) is a major pathogenic bacteria that causes nosocomial infections. Therefore, L. monocytogenes and MRSA are currently of great concern. The present study aimed to determine whether B. amyloliquefaciens JN68 extracts could inhibit L. monocytogenes and MRSA. The results indicated that extracts of B. amyloliquefaciens JN68 have CLP components, and can successfully inhibit the growth of L. monocytogenes and MRSA.


Assuntos
Anti-Infecciosos/farmacologia , Bacillus amyloliquefaciens/metabolismo , Lipopeptídeos/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Anti-Infecciosos/isolamento & purificação , Antibiose , Bacillus amyloliquefaciens/isolamento & purificação , Galinhas , Intestinos/microbiologia , Lipopeptídeos/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação
17.
Mol Med Rep ; 13(6): 5372-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27109695

RESUMO

Renal fibroblast proliferation is key in renal fibrosis and chronic kidney disease. Transforming growth factor-ß1 (TGF-ß1) has been demonstrated to be an important factor that induces cell proliferation in renal fibroblasts. Epidermal growth factor receptor (EGFR) is also recognized as a factor promoting renal fibroblast proliferation. In addition, mitogen­activated protein kinase signaling pathways are associated with TGF­ß1­ and EGFR­induced cell proliferation. Gefitinib, an EGFR tyrosine kinase inhibitor, is predominantly used as an anti­tumor therapeutic agent in clinical therapeutic strategies. However, gefitinib has been suggested to exert anti­proliferative effects on renal fibroblasts, however, high­dose gefitinib may result in serious side effects. The present study aims to determine whether low­dose gefitinib reduces gefitinib­induced side effects and maintains the anti­proliferative effects on renal fibroblasts. TGF­ß1 promotes cell proliferation in renal fibroblasts, and the current study demonstrates that low­dose gefitinib treatment exhibits anti­proliferative effects similar to those of high­dose gefitinib treatment. Thus, although high­dose gefitinib is a conventional anti­tumor drug, low­dose gefitinib may be of use in renal fibrosis treatment. Furthermore, the present study demonstrates that a combined treatment with low-dose gefitinib and vitamin E has synergistic effects that reduce TGF­ß1­induced fibroblast proliferation, cell-cycle arrest and the ERK phosphorylation pathway.


Assuntos
Proliferação de Células/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/metabolismo , Quinazolinas/farmacologia , Fator de Crescimento Transformador beta1/biossíntese , Vitamina E/farmacologia , Animais , Linhagem Celular , Sinergismo Farmacológico , Fibroblastos/citologia , Gefitinibe , Rim/citologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quinazolinas/agonistas , Ratos , Vitamina E/agonistas
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 35(4): 591-3, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25907951

RESUMO

OBJECTIVE: To explore the methods for constructing the digital three-dimensional model of fetal heart. METHODS: Original two-dimensional CT image data sets were collected from 4 abortion fetuses with fetal malformations but not heart malformation or chromosomal abnormalities. The three-dimensional fetal heart model was reconstructed using Mimics14.0 software. RESULTS: In the reconstructed three-dimensional fetal heart, the left atrium, left ventricle, right atrium, right ventricle, the ascending aorta, the main pulmonary and their branches, the superior cava and inferior vena cava were marked with different colors, and these structures could be displayed individually or with other structures. This model also allowed three-dimensional arbitrary scaling, shifting or rotation at any angle, and the diameter of the each vessel could be measured with the software. CONCLUSION: The fetal heart model can be successfully reconstructed from the CT datasets using three-dimensional reconstruction software to facilitate clinical and anatomical teaching.


Assuntos
Coração Fetal/anatomia & histologia , Imageamento Tridimensional , Modelos Anatômicos , Feminino , Átrios do Coração/anatomia & histologia , Cardiopatias Congênitas , Ventrículos do Coração/anatomia & histologia , Humanos , Gravidez , Software , Tomografia Computadorizada por Raios X , Veia Cava Inferior/anatomia & histologia
19.
Shock ; 43(4): 405-11, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25514429

RESUMO

Alpha-lipoic acid (ALA), a naturally occurring disulfide derivative of octanoic acid, serves as a strong antioxidant and has been reported to possess anti-inflammatory effects. The aim of the present study is to investigate the preventive and therapeutic effects of ALA on multiple organ dysfunction syndrome (MODS) caused by endotoxemia in rats. Male Wistar rats were intravenously infused with lipopolysaccharide (LPS) (10 mg/kg) to induce endotoxemia. Alpha-lipoic acid 10, 20, or 40 mg/kg was administered intravenously 60 min before (pretreatment) LPS challenge, and ALA 40 mg/kg was administered intravenously 30 min after (posttreatment) LPS challenge. Pretreatment and posttreatment with ALA significantly improved the deleterious hemodynamic changes 8 h after LPS challenge, including hypotension and bradycardia. Alpha-lipoic acid reduced the plasma levels of glutamic pyruvic transaminase, blood urea nitrogen, lactate dehydrogenase, tumor necrosis factor-α, nitric oxide metabolites, and thrombin-antithrombin complex, which increased markedly after LPS challenge. The induction of inducible nitric oxide synthase both in the liver and the lung and vascular superoxide anion production were also significantly suppressed by ALA. Moreover, ALA significantly attenuated LPS-induced caspase-3 activation in cardiomyocytes and improved survival rate. In conclusion, ALA effectively attenuated LPS-induced acute inflammatory response and improved MODS. The antioxidant and anti-inflammatory effects of ALA may contribute to these beneficial effects. Alpha-lipoic acid might be considered as a novel therapeutic strategy in the prevention of sepsis-induced MODS and inflammatory vascular diseases.


Assuntos
Endotoxemia/complicações , Insuficiência de Múltiplos Órgãos/prevenção & controle , Choque Séptico/prevenção & controle , Ácido Tióctico/farmacologia , Animais , Antioxidantes/farmacologia , Antitrombinas/química , Aorta/metabolismo , Caspase 3/metabolismo , Dissulfetos/química , Ativação Enzimática , Hemodinâmica , Inflamação/metabolismo , Fígado/enzimologia , Pulmão/enzimologia , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Miocárdio/enzimologia , Nitratos/química , Nitritos/química , Ratos , Ratos Wistar , Sepse/fisiopatologia , Choque Séptico/etiologia , Superóxidos/química , Trombina/química
20.
Biomed Res Int ; 2013: 201614, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24371817

RESUMO

Sepsis can cause myocardial dysfunction, which contributes to the high mortality of sepsis. Hypertonic saline (HS) has been reported to increase myocardial contractility in sepsis. In the present study, mechanisms of action of HS resuscitation (4 mL of 7.5% NaCl per kilogram) on cardiac function have been evaluated in septic rats. HS was administered 1 h after LPS (10 mg/kg, i.v.) challenge. The mean arterial blood pressure significantly decreased 4 h after LPS challenge, and septic shock was observed at the end of experiment (6 h). Posttreatment with HS prevented hypotension caused by LPS and significantly improved cardiac function, evidenced by increases in left ventricular developed pressure, mean +dP/dt and -dP/dt. The amplitude of electrical-stimulated intracellular Ca(2+) transient in isolated single cardiomyocytes was significantly reduced after 6 h LPS insult, which was recovered by HS. In addition, LPS resulted in significant increases in neutrophil myeloperoxidase activity, macrophage migration inhibitory factor (MIF), and NF-κB phospho-p65 protein levels in myocardium at 6 h, which were significantly attenuated by HS. In conclusion, HS improved myocardial contractility and prevented circulatory failure induced by endotoxemia, which may attribute to improvement of intracellular calcium handling process and inhibitory effects on neutrophil infiltration and MIF production in hearts.


Assuntos
Fatores Inibidores da Migração de Macrófagos/antagonistas & inibidores , Solução Salina Hipertônica/administração & dosagem , Sepse/tratamento farmacológico , Animais , Cálcio/metabolismo , Humanos , Hipotensão/induzido quimicamente , Hipotensão/tratamento farmacológico , Hipotensão/patologia , Lipopolissacarídeos/toxicidade , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Sepse/induzido quimicamente , Sepse/patologia
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