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1.
Environ Res ; 184: 109304, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32192988

RESUMO

Ambient air pollution has been a major concern in China due to its effect on population health. Exposure to ambient air pollution has negative impact on animal reproduction and fertility, however, its effect on human reproduction has been inconclusive. We conducted a retrospective study on in vitro fertilization (IVF) patients from Chengdu, Sichuan Province in western China, a city with persistent ambient air pollution. We analyzed the medical records of 1139 patients who underwent first conventional IVF cycles during 2014-2019. The relationship between six atmospheric pollutants (PM2.5, PM10, O3, NO2, SO2, CO) and IVF pregnancy outcomes were assessed by 1) stratification of maternal age into three groups (<35, 35-39, ≥40 years), and by 2) averaging pollutant concentration during different exposure windows. The results indicate that the association between ambient air pollution and IVF pregnancy outcomes (biochemical pregnancy and clinical pregnancy) is more significant for women in <35 years age group. Concentrations of PM2.5, PM10, NO2, SO2 and CO are negatively associated with the odds of biochemical pregnancy and clinical pregnancy, and concentration of CO in particular is associated with the largest reduction in odds. Conversely, O3 concentration is positively associated with biochemical pregnancy and clinical pregnancy. Moreover, pollutant concentration during long-term exposure window is associated with larger magnitude of change in the odds of biochemical pregnancy and clinical pregnancy. Findings from this study suggest that exposure to ambient air pollution during any period within the IVF treatment timeline would influence IVF pregnancy outcomes, and such influence is more pronounced in younger women (<35 years).

2.
Molecules ; 25(4)2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32079098

RESUMO

Protein kinase (CK2) has emerged as an attractive cancer therapeutic target and recent efforts have been made to develop its inhibitors. However, the development of selective inhibitors remains challenging because of the highly conserved ATP-binding pocket (orthosteric site) of kinase family. As an alternative strategy, allosteric inhibitors, by targeting the much more diversified allosteric site relative to the conserved ATP-binding site, achieve better pharmacological advantages than orthosteric inhibitors. Traditional serendipitous screening and structure-based design are robust tools for the discovery of CK2 allosteric inhibitors. In this review, we summarize the recent advances in the identification of CK2 allosteric inhibitors. Firstly, we briefly present the CK2 allosteric sites. Then, the allosteric inhibitors targeting the well-elucidated allosteric sites (α/ß interface, αD pocket and interface between the Glycine-rich loop and αC-helix) are highlighted in the discovery process and possible binding modes with the allosteric sites are described. This study is expected to provide valuable clues for the design of CK2 allosteric inhibitors.

3.
ACS Nano ; 14(2): 2063-2076, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32022535

RESUMO

Ultrasound (US)-driven sonodynamic therapy (SDT) has demonstrated wide application prospects in the eradication of deep-seated bacterial infections due to its noninvasiveness, site-confined irradiation, and high-tissue-penetrating capability. However, the ineffective accumulation of sonosensitizers at the infection site, the hypoxic microenvironment, as well as rapid depletion of oxygen during SDT greatly hamper the therapeutic efficacy of SDT. Herein, an US-switchable nanozyme system was proposed for the controllable generation of catalytic oxygen and sonosensitizer-mediated reactive oxygen species during ultrasound activation, thereby alleviating the hypoxia-associated barrier and augmenting SDT efficacy. This nanoplatform (Pd@Pt-T790) was easily prepared by bridging enzyme-catalytic Pd@Pt nanoplates with the organic sonosensitizer meso-tetra(4-carboxyphenyl)porphine (T790). It was really interesting to find that the modification of T790 onto Pd@Pt could significantly block the catalase-like activity of Pd@Pt, whereas upon US irradiation, the nanozyme activity was effectively recovered to catalyze the decomposition of endogenous H2O2 into O2. Such "blocking and activating" enzyme activity was particularly important for decreasing the potential toxicity and side effects of nanozymes on normal tissues and has potential to realize active, controllable, and disease-loci-specific nanozyme catalytic behavior. Taking advantage of this US-switchable enzyme activity, outstanding accumulation in infection sites, as well as excellent biocompatibility, the Pd@Pt-T790-based SDT nanosystem was successfully applied to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced myositis, and the sonodynamic therapeutic progression was noninvasively monitored by photoacoustic imaging and magnetic resonance imaging. The developed US-switchable nanoenzyme system provides a promising strategy for augmenting sonodynamic eradication of deep-seated bacterial infection actively, controllably, and precisely.

4.
Nanoscale ; 12(6): 3916-3930, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32003377

RESUMO

Palladium nanosheets (Pd NSs) have recently attracted increasing research interest in the biomedical field due to their excellent near-infrared absorption, photothermal conversion capability and biocompatibility. However, the application of Pd NSs in immunotherapy has not been reported. Here, Pd NSs were used as the carriers of immunoadjuvant CpG ODNs for not only efficient delivery of CpG but also for enhancing the immunotherapeutic effects of CpG by the Pd NS-based photothermal therapy (PTT). Pd NSs had no influence on the immune system, and the prepared Pd-CpG nanocomposites, especially Pd(5)-CpG(PS), could significantly increase the uptake of CpG by immune cells and enhance the immunostimulatory activity of CpG in vitro and in vivo. With the combination of Pd(5)-CpG(PS) mediated PTT and immunotherapy, highly efficient tumor inhibition was achieved and the survival rate of the tumor-bearing mice was greatly increased depending on Pd(5)-CpG(PS) with safe near-infrared (NIR) irradiation (808 nm laser, 0.15 W cm-2). Importantly, the combination therapy induced tumor cell death and released tumor-associated antigens, which could be effectively taken up and presented by antigen presenting cells with the assistance of CpG, leading to increased TNF-α and IL-6 production and enhanced cytotoxic T lymphocyte (CTL) activity. This work provides a new paradigm of utilizing photothermal nanomaterials for safe and highly efficient cancer photothermal combined immunotherapy.

5.
Am J Sports Med ; 48(5): 1141-1150, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32074471

RESUMO

BACKGROUND: The pathogenesis of patellar tendon fibrosis caused by overuse remains unclear. In an effort to further investigate effective treatments for patellar tendon fibrosis attributed to overuse, it is necessary to construct a reliable animal model. PURPOSE: A rabbit patellar tendon fibrosis model was developed with the use of electrical stimulation to induce jumping. The pathogenesis and development of patellar tendon fibrosis were subsequently investigated with this model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 32 New Zealand White rabbits were randomly divided into a jumping group and a control group. Rabbits in the control group did not receive any treatment, while those in the jumping group jumped 150 times daily, 5 days per week. At 2, 4, 6, and 8 weeks after the initiation of treatment, the patellar tendons of 4 rabbits from each group were harvested and subjected to hematoxylin and eosin staining, immunohistochemical staining, and real-time polymerase chain reaction. The influence of jumping training on the expressions of histology- and fibrosis-related factors in the patellar tendon was assessed. RESULTS: The histological changes of patellar tendon fibrosis in the jumping group were most pronounced at 4 weeks. When compared with the control group at corresponding time points, the mRNA and protein expressions of TGF-ß1, CTGF, COL-I, and COL-III were upregulated significantly in the patellar tendon after jumping training for 4 weeks (P < .05). Intragroup comparison at different time points indicated that the mRNA and protein expressions of TGF-ß1, COL-I, and COL-III were the highest at 4 weeks in the jumping group (P < .01). CONCLUSION: It was found that patellar tendon fibrosis occurred because of overuse and the peak changes occurred at 4 weeks. Jumping load increased the secretions of TGF-ß1 and Smad3 in the patellar tendon, with CTGF upregulation and higher synthesis of COL-I and COL-III, which were considered the pathogenesis of fibrosis. CLINICAL RELEVANCE: This study simulated the effects of jumping load on tendon fibrosis at different time points. Moreover, the time course relationship between jumping training and patellar tendon fibrosis in the rabbit model was determined, which provided a new animal model for the study of patellar tendon fibrosis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31934802

RESUMO

Purpose: Dry eye disorders are a major health care burden. We previously reported the identification of N-methyl-N-phenyl-6-(2,2,3,3-tetrafluoropropoxy)-1,3,5-triazine-2,4-diamine [cystic fibrosis transmembrane conductance regulator (CFTR)act-K267], which activated human wild-type CFTR chloride conductance with EC50 ∼ 30 nM. Here, we report in vivo evidence for CFTRact-K267 efficacy in an experimental mouse model of dry eye using a human compatible ophthalmic vehicle. Methods: CFTR activation in mice in vivo was demonstrated by ocular surface potential difference (OSPD) measurements. Ocular surface pharmacodynamics was measured in tear fluid samples obtained at different times after topical administration of CFTRact-K267. Dry eye was produced by lacrimal duct cautery (LDC) and corneal epithelial injury and was assessed by Lissamine green (LG) staining. Results: OSPD measurements demonstrated a hyperpolarization of -8.6 ± 3 mV (standard error of the mean, 5 mice) in response to CFTRact-K267 exposure in low chloride solution that was reversed by a CFTR inhibitor. Following single-dose topical administration of 2 nmol CFTRact-K267, tear fluid CFTRact-K267 concentration was >500 nM for more than 6 h. Following LDC, corneal surface epithelial injury, as assessed by LG staining, was substantially reversed in 10 of 12 eyes receiving 2 nmol CFTRact-K267 3 times daily starting on day 2, when marked epithelial injury had already occurred. Improvement was seen in 3 of 12 vehicle-treated eyes. Conclusion: These studies provide in vivo evidence in mice for the efficacy of a topical, human use compatible CFTRact-K267 formulation in stimulating chloride secretion and reversing corneal epithelial injury in dry eye.

7.
Planta ; 251(2): 42, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907619

RESUMO

Main conclusion: Jasmonic acid (JA) negatively regulates stomatal development by promoting LCD expression and hydrogen sulfide (H2S) biosynthesis. H2S inhibits the initiation of stomata formation and acts upstream of SPEECHLESS. Abstract: Stomatal development is strictly regulated by endogenous signals and environmental cues. We recently revealed that jasmonic acid (JA) negatively regulates stomatal development in Arabidopsis thaliana cotyledons (Han et al., Plant Physiol 176:2871-2885, 2018), but the underlying molecular mechanism remains largely unknown. Here, we uncovered a role for H2S in regulating stomatal development. The H2S scavenger hypotaurine reversed the JA-induced repression of stomatal development in the epidermis of wild-type Arabidopsis. The H2S-deficient mutant lcd displayed increased stomatal density and stomatal index values, which were rescued by treatment with sodium hydrosulfide (NaHS; an H2S donor) but not JA, suggesting that JA-mediated repression of stomatal development is dependent on H2S biosynthesis. The high stomatal density of JA-deficient mutants was rescued by exogenous NaHS treatment. Further analysis indicated that JA positively regulates LCD expression, L-cysteine desulfhydrases (L-CDes) activity, and endogenous H2S content. Furthermore, H2S represses the expression of stomate-associated genes and functions downstream of stomate-related signaling pathway components TOO MANY MOUTHS (TMM) and STOMATAL DENSITY AND DISTRIBUTION1 (SDD1) and upstream of SPEECHLESS (SPCH). Therefore, H2S acts downstream of JA signaling to regulate stomatal development in Arabidopsis cotyledons.

8.
Mol Med Rep ; 21(2): 795-805, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974601

RESUMO

The aim of the present study was to investigate the involvement of B cell­activating factor (BAFF) in the pathogenesis of IgA nephropathy by activating the tumor necrosis factor receptor­associated factor 6 (TRAF6)/NF­κB signaling pathway in glomerular mesangial cells. For the clinical analysis, blood, urine and kidney tissue samples were collected from 58 patients diagnosed with primary IgA nephropathy by renal biopsy. For the in vitro study, glomerular mesangial cells were divided into five groups: Control (con)­short hairpin RNA (shRNA) (control group); con­shRNA + BAFF (20 ng/ml); con­shRNA + BAFF + BAFF­RFc chimera protein (500 µg/ml); TRAF6­shRNA; and TRAF6­shRNA + BAFF (20 ng/ml). For the in vivo experiments, 60 Sprague­Dawley rats were randomly divided into four groups: Con­small interfering RNA (siRNA) (control group); con­siRNA + IgA (IgA nephropathy group), BAFF­RFc chimera protein (2 µg/ml) + IgA, and TRAF6­siRNA (0.2 µM) + IgA. Reverse transcription­quantitative PCR was performed to evaluate the mRNA expression levels of TRAF6, connective tissue growth factor (CTGF), fibronectin (FN) and NF­κBP65. Western blot analysis was used to detect the protein expression levels of TRAF6, FN, CTGF and phosphorylated­NF­κBP65 in glomerular mesangial cells and kidney tissues. The results revealed that plasma BAFF levels were positively correlated with the severity of pathological damage in patients with IgA nephropathy. In vitro, BAFF induced the mRNA and protein expression of TRAF6, CTGF, FN and NF­κBP65 in glomerular mesangial cells. After the BAFF­RFc chimera protein was added to inhibit the binding of BAFF and BAFF­receptor (­R), this effect was reduced. In vivo, inhibition of the effects of BAFF via injection with the BAFF­R Fc chimera protein reduced kidney damage in rats suffering from IgA nephropathy. The effect on the expression of signaling pathway­associated proteins was also alleviated. In conclusion, BAFF enhanced the expression of fibroblast factors in the kidneys by activating the TRAF6/NF­κB signaling pathway.

9.
Biofactors ; 46(1): 168-179, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31688999

RESUMO

Left ventricular remodeling commonly complicates end-stage renal disease following chronic kidney disease (CKD). This study investigated the therapeutic efficacy of resveratrol (RSV), a polyphenolic compound, on left ventricular remodeling in subtotal nephrectomy rats and sought to uncover the underlying molecular mechanisms. Subtotal nephrectomy caused renal dysfunction, such as gradual increases in serum creatinine and blood urea nitrogen, glomerular sclerosis, and tubulointerstitial fibrosis. In addition, subtotal nephrectomy also resulted in significant increases in myocyte cross-sectional area, interstitial and perivascular fibrosis, and left ventricular dilatation. All these detrimental effects were alleviated in the presence of RSV. Mechanistically, RSV treatment led to the upregulation of manganese-containing superoxide dismutase (MnSOD) in the heart. Coimmunoprecipitation studies showed that silent information regulator 1 (Sirt1) bound forkhead box protein O1 (FoxO1) and thus reduced acetylated FoxO1. RSV strengthened this interaction between Sirt1 and FoxO1. Loss of one allele of Sirt1 aggravated renal damage, myocyte hypertrophy, and interstitial fibrosis in nephrectomized mice. Taken together, our data show that Sirt1 is an important mediator for the protective roles of RSV on renal and heart damage in CKD rodent model, and FoxO1 and MnSOD are likely downstream targets of Sirt1. Therefore, Sirt1 might be a potential therapeutic target for the treatment of left ventricular remodeling caused by CKD.

10.
Nutr Metab Cardiovasc Dis ; 30(3): 393-399, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-31791635

RESUMO

BACKGROUND AND AIMS: The prognostic nutritional index (PNI) had been associated with adverse outcomes in numerous clinical conditions. However, its influence on idiopathic dilated cardiomyopathy (DCM) was not determined. This aim of this study was to determine the predictive ability of PNI in patients with idiopathic DCM. METHODS AND RESULTS: A total of 1021 consecutive patients with idiopathic DCM were retrospectively included and divided into three groups based on admission PNI tertiles: <41.7 (n = 339), 41.7-47.3 (n = 342), >47.3 (n = 340). The association of PNI with in-hospital major adverse clinical events (MACEs) and death during follow-up was evaluated. In-hospital mortality (2.9% vs. 1.5% vs. 0.0%, respectively; p = 0.006) and MACEs (13.6% vs. 6.7% vs. 3.5%, respectively; p < 0.001) decreased from the lowest to the highest PNI tertile. The optimal cut-off value of PNI to predict in-hospital MACEs was 44.0 (area under the curve: 0.689; 95% confidence interval [CI]: 0.626-0.753; p < 0.001). Multivariate analysis showed that a PNI≤44.0 was an independent risk factor of in-hospital MACEs (odd ratio: 2.86; 95% CI: 1.64-4.98; p < 0.001) and all-cause mortality at a median follow-up of 27 months (hazard ratio: 1.67; 95% CI: 1.11-2.49; p = 0.013). In addition, patients with a PNI≤44.0 had a lower cumulative survival rate during follow-up (log-rank: 35.62; p < 0.001). CONCLUSION: The PNI was an independent risk factor for in-hospital MACEs and all-cause mortality at a median follow-up of 27 months in patients with idiopathic DCM; hence, it may be considered a tool for risk assessment.

11.
ChemSusChem ; 13(2): 298-303, 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31713317

RESUMO

The introduction of phosphorus functional groups into the skeleton of thioflavones is an attractive task and of great significance. Herein, a metal-free visible-light-induced radical cascade cyclization was developed for the preparation of 2-phosphorylated thioflavones from methylthiolated alkynones and phosphine oxides. In water as a green reaction medium, a large number of such 2-phosphorylated thioflavones were prepared, catalyzed by 4CzIPN [1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene] under visible-light irradiation. These reactions could be performed at ambient temperature and feature simple operation, wide reaction scope, and recyclability of aqueous media.

12.
Microvasc Res ; 127: 103923, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31494123

RESUMO

Minimally modified low-density lipoprotein (mmLDL) is a risk factor for cardiovascular disease. This study was designed to investigate the effect of a Toll-like receptor 4 monoclonal antibody (TLR4 mAb) on mmLDL-induced endothelium-dependent vasodilation (EDV) impairment in mouse mesenteric arteries and to explore the underlying mechanism. Animals were divided into a normal control group, an mmLDL treatment group, and a TLR4 mAb intervention group. The serum concentrations of IL-1ß and TNF-α were detected using enzyme-linked immunosorbent assays (ELISAs). EDV function was measured using a microvascular tension tracing method. The protein levels and mRNA expression of IL-1ß and TNF-α in vascular tissue were detected using western blot analysis and reverse transcription polymerase chain reaction, respectively. TLR4 mAb improved mmLDL-induced EDV functional impairment in a dose-dependent manner. TLR4 mAb significantly upregulated KCa3.1 and KCa2.3 channel protein levels and downregulated TNF-α and IL-1ß expression. These effects were possibly associated with the competitive antagonism of TLR4 mAb on the TLR4 signaling pathway and the downstream NF-κB p65 and p38 MAPK pathways, which are activated by mmLDL. In conclusion, pretreatment with TLR4 mAb lessens mmLDL-induced EDV dysfunction and inhibits overexpression of inflammatory factors. Regulation of the TLR4 pathway, as well as its downstream NF-κB p65 and p38 MAPK pathways, may be an effective strategy for the prevention and treatment of cardiovascular diseases.

13.
Drug Deliv ; 26(1): 1104-1114, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31735104

RESUMO

Nanoemulgels are composed of O/W nanoemulsion and hydrogels and are considered as ideal carriers for the transdermal drug delivery because these have high affinity to load hydrophobic drugs. The stable formulation of eprinomectin (EPR) is very challenging because of it is high hydrophobic nature. In this work, we have prepared EPR loaded nanoemulgel for the treatment of endo- and ectoparasites. The surface morphology of optimized formulations was characterized by scanning electron microscopy. Additionally, skin permeability and irritation tests were conducted for in vitro safety and in vivo skin retention and pearmeation test of EPR nanoemulgel were conducted for efficacy study. Obtained results indicated that the optimized formulation had good shear-thinning behavior, bioadhesiveness properties, and are nanosized droplets with porous internal structure, which are required for topical application. Furthermore, this formulation has showed good skin permeability in comparison to suspension and has no skin irritating property. Overall, the obtained results proved that nanoemulgel is a promising carrier for transdermal drug delivery and EPR nanoemulgel is a promising formulation for the treatment of endo- and ectoparasites.


Assuntos
Emulsões/química , Géis/química , Ivermectina/análogos & derivados , Pele/metabolismo , Administração Cutânea , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Emulsões/administração & dosagem , Géis/administração & dosagem , Ivermectina/administração & dosagem , Ivermectina/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nanopartículas/química , Permeabilidade , Ratos , Ratos Sprague-Dawley , Absorção Cutânea
14.
Chem Commun (Camb) ; 55(84): 12615-12618, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31580369

RESUMO

A metal-free cascade reaction was developed for the synthesis of indolo[1,2-a]quinoline derivatives from arylsulfonyl hydrazides and 1-(2-(arylethynyl)phenyl)indoles in the presence of TBAI/TBHP. Impressively, these products exhibit excellent fluorescence properties, which is promising for cell imaging.

15.
J Vet Pharmacol Ther ; 42(6): 732-737, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31490576

RESUMO

The aim of the research was to investigate the anti-endotoxin and anti-inflammatory effects of Sinomenine, an agent commonly found in Chinese herbal medicines. Endotoxin (i.e., 1 mg lipopolysaccharide (LPS)/kg)) was administered via intraperitoneal (IP) injection to piglets in high-, middle-, and low-dose sinomenine groups. Piglets were then treated with 1, 5 or 10 mg/kg sinomenine, intramuscularly (i.m.), 3 hr after LPS. Vehicle was administered, as above, to drug control group piglets followed 3 hr later by 10 mg/kg sinomenine i.m.. LPS control group piglets were challenged with 1 mg/kg LPS IP, followed by vehicle i.m., and naïve control piglets were treated with normal saline IP, followed by normal saline i.m., as above. Temperatures were measured, and blood samples were collected from the precaval veins of piglets at 12, 24, and 48 hr post-LPS or vehicle injection. Clinical signs were recorded, and index levels were analyzed via ELISA. Sinomenine was found to reduce the incidence and severity of LPS-induced toxicities, including body temperature elevation, cell adhesion, and systemic inflammation. These data suggest that sinomenine may be effective for regulating inflammatory responses and has the potential for use as an anti-endotoxin therapy.

16.
Sci Rep ; 9(1): 12549, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467329

RESUMO

Our understanding of diabetic kidney disease pathogenesis has been hampered by the lack of easily generated pre-clinical animal models that faithfully recapitulate critical features of human disease. While most standard animal models develop manifestations of early stage diabetic injury such as hyperfiltration and mesangial matrix expansion, only a select few develop key late stage features such as interstitial fibrosis and reduced glomerular filtration rate. An underlying theme in these late stage disease models has been the addition of renin-angiotensin system hyperactivation, an important contributor to human disease pathogenesis. Widespread use of these models has been limited, however, as they are either labour intensive to generate, or have been developed in the rat, preventing the use of the many powerful genetic tools developed for mice. Here we describe the Akita+/- Ren+/- mouse, a new, easily generated murine model of diabetic kidney disease that develops many features of late stage human injury, including not only hyperglycemia, hypertension, and albuminuria, but also reduced glomerular filtration rate, glomerulosclerosis, and interstitial fibrosis.

17.
Rev Assoc Med Bras (1992) ; 65(7): 988-992, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31389510

RESUMO

OBJECTIVE: The objective of this study was to investigate the effects of low triiodothyronine syndrome (LT3S) on platelet function and clotting factors in patients with nephrotic syndrome(NS). METHODS: Patients with primary nephrotic syndrome were divided into two groups, normal thyroid function (group A) and LT3S (group B), based on whether they had LT3S or not. Healthy subjects were selected as the control group (group C). Blood coagulation function was detected in each group. The platelet activation function (CD62P, CD63) was determined by flow cytometry. The platelet aggregation rate was detected by an optical method using adenosine diphosphate and arachidonic acid as inducers. RESULTS: The proportion of primary nephrotic syndrome with LT3S was 23.2% (69/298). Compared with group C, group A had higher CD62P and PAgTADP, and group B had higher CD62P, CD63, PAgTAA, and PAgTADP; the difference was statistically significant (all P < 0.05). There was no significant difference in renal pathology between group A and group B (X2 = 4.957, P = 0.421). Compared with group A, the 24-hour urine protein, CD63, PAgTAA, and PAgTADP were higher in group B, and APTT and Alb were lower. The difference was statistically significant (P < 0.05). Logistic regression analysis showed that LT3S was associated with CD36 (OR: 3.516; 95% CI: 1.742~8.186; P = 0.004) and PAgTAA (OR: 0.442; 95% CI: 1.001~1.251; P = 0.037). CONCLUSION: NS patients are prone to LT3S. Patients with LT3S may have abnormal platelet activation and increase of platelet aggregation.


Assuntos
Plaquetas/fisiologia , Síndromes do Eutireóideo Doente/sangue , Síndromes do Eutireóideo Doente/fisiopatologia , Síndrome Nefrótica/sangue , Síndrome Nefrótica/fisiopatologia , Tri-Iodotironina/sangue , Adulto , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/complicações , Ativação Plaquetária/efeitos dos fármacos , Ativação Plaquetária/fisiologia , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/fisiologia , Contagem de Plaquetas , Testes de Função Plaquetária , Valores de Referência , Análise de Regressão , Tri-Iodotironina/deficiência
18.
Poult Sci ; 98(10): 5109-5117, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265733

RESUMO

FOXO3 belongs to the Forkhead O transcription factor family and it is an important gene in multiple biological processes, such as cell cycle control, cell proliferation, cell apoptosis, human longevity, and oxidative stress. Previous studies have shown that FOXO3 is associated with skeletal muscle growth and adipose development in mammals. However, the sequence of chicken FOXO3 is still incomplete and the cellular functions of FOXO3 in chickens are poorly understood. Thus, we obtained the full-length sequence of chicken FOXO3 by 5' rapid amplification of cDNA ends (5' RACE) and the phylogenetic tree showed that the chicken FOXO3 sequence was homologous with those in other species. Flow cytometry analysis and 5-ethynyl-2'-deoxyuridine assays showed that FOXO3 repressed cellular proliferation and induced apoptosis in a chicken hepatocellular carcinoma cell line (LMH). Mutations were screened in the second exon of FOXO3 and 13 synonymous single nucleotide polymorphisms were found in the test population. Further analysis showed that rs317670452 and rs15379317 were associated with many growth and carcass traits, such as the body weight at different ages and breast muscle weight. Our results indicate that chicken FOXO3 has similar cellular functions to those found in mammals and it is significantly associated with chicken growth.


Assuntos
Apoptose/genética , Proteínas Aviárias/genética , Proliferação de Células/genética , Galinhas/genética , Proteína Forkhead Box O3/genética , Carne/análise , Animais , Proteínas Aviárias/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Proteína Forkhead Box O3/metabolismo , Filogenia , Polimorfismo de Nucleotídeo Único
19.
Rev. Assoc. Med. Bras. (1992) ; 65(7): 988-992, July 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1013006

RESUMO

SUMMARY OBJECTIVE The objective of this study was to investigate the effects of low triiodothyronine syndrome (LT3S) on platelet function and clotting factors in patients with nephrotic syndrome(NS). METHODS Patients with primary nephrotic syndrome were divided into two groups, normal thyroid function (group A) and LT3S (group B), based on whether they had LT3S or not. Healthy subjects were selected as the control group (group C). Blood coagulation function was detected in each group. The platelet activation function (CD62P, CD63) was determined by flow cytometry. The platelet aggregation rate was detected by an optical method using adenosine diphosphate and arachidonic acid as inducers. RESULTS The proportion of primary nephrotic syndrome with LT3S was 23.2% (69/298). Compared with group C, group A had higher CD62P and PAgTADP, and group B had higher CD62P, CD63, PAgTAA, and PAgTADP; the difference was statistically significant (all P < 0.05). There was no significant difference in renal pathology between group A and group B (X2 = 4.957, P = 0.421). Compared with group A, the 24-hour urine protein, CD63, PAgTAA, and PAgTADP were higher in group B, and APTT and Alb were lower. The difference was statistically significant (P < 0.05). Logistic regression analysis showed that LT3S was associated with CD36 (OR: 3.516; 95% CI: 1.742~8.186; P = 0.004) and PAgTAA (OR: 0.442; 95% CI: 1.001~1.251; P = 0.037). CONCLUSION NS patients are prone to LT3S. Patients with LT3S may have abnormal platelet activation and increase of platelet aggregation.


RESUMO OBJETIVO O objetivo deste estudo foi investigar os efeitos da síndrome do baixo triiodotironina (LT3S) na função plaquetária e nos fatores de coagulação em pacientes com síndrome nefrótica (SN). MÉTODOS Pacientes com síndrome nefrótica primária foram divididos em dois grupos, função tireoidiana normal (grupo A) e LT3S (grupo B), com base na presença ou não de LT3S. Indivíduos saudáveis foram selecionados como grupo de controle (grupo C). A função de coagulação do sangue foi analisada em cada grupo. A função de ativação plaquetária (CD62P, CD63) foi determinada por citometria de fluxo. A taxa de agregação plaquetária foi detectada por um método óptico usando adenosina difosfato e ácido araquidônico como indutores. RESULTADOS A proporção de síndrome nefrótica primária com LT3S foi de 23,2% (69/298). Em comparação com o grupo C, o grupo A apresentou níveis mais altos de CD62P e PAgTADP, e o grupo B apresentou maiores CD62P, CD63, PAgTAA e PAgTADP; a diferença teve significância estatística (P < 0,05). Não houve diferença significativa na patologia renal entre o grupo A e o grupo B (X2 = 4,957, P = 0,421). Em comparação com o grupo A, a proteína em urina de 24 horas, CD63, PAgTAA e PAgTADP foram maiores no grupo B, já APTT e Alb foram mais baixos. A diferença apresentou significância estatística (P < 0,05). A análise de regressão logística mostrou uma associação entre LT3S e CD36 (OR: 3,516; 95% IC: 1,742~8,186; P = 0,004) e PAgTAA (OR: 0,442; 95% IC: 1,001~1,251; P = 0,037). CONCLUSÃO Pacientes com síndrome nefrótica estão propensos à síndrome do baixo triiodotironina (LT3S). Pacientes com LT3S podem ter ativação plaquetária anormal e aumento da agregação plaquetária.

20.
Biomaterials ; 216: 119266, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220795

RESUMO

iPSCs-derived insulin-producing cell transplantation is a promising strategy for diabetes therapy. Although there have been many protocols of mature, glucose-responsive ß cells induced in vitro over the past few years, many underlying problems remain to be resolved. As a crucial regulator, long noncoding RNAs (lncRNAs) participate in numerous biological processes, including the maintenance of pluripotency, and stem cell differentiation. In this study, we identified a novel lncRNA Gm10451 as a functional regulator for ß-like cell differentiation. Localized to the cytoplasm, Gm10451 regulates histone H3K4 methyltransferase complex PTIP to facilitate Insulin+/Nkx6.1+ ß-like cell differentiation by targeting miR-338-3p as a competing endogenous RNA (ceRNA). miR-338-3p has also been shown to suppress Nkx6.1+ early-stage ß-like cell differentiation by targeting PTIP. Following transplantation into streptozotocin (STZ)-mice, Gm10451 loss in ß-like cells prevented the expression of mature ß-cell makers, such as Insulin, Nkx6.1, and Mafa. Accordingly, hyperglycemia in the mice was not resolved. Taken together, this study provides an efficient epigenetic target for generating more mature and functional iPSCs-derived ß-like cells. We anticipate that pancreatic organoids, which are generated from human stem cells, biological materials, and epigenetic modifications, can be used in the future as a novel diabetes treatment option.

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