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1.
Dev Comp Immunol ; 126: 104238, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34428528

RESUMO

Previous studies have shown that protein disulfide isomerase (PDI), a member of the thioredoxin (TRX) superfamily, are broadly associated with immune responses in a variety of animals. However, it remains largely unknown about the direct roles of PDIs during a bacterial infection. In this study, we identified the presence of a single pdi gene in the amphioxus Branchiostoma japonicum, Bjpdi. The deduced protein BjPDI is structurally characterized by the presence of four Trx-like domains in the order of a, b, b' and a' and a short acidic C-terminal tail, that are characteristic of PDIs. We demonstrated that rBjPDI displayed both thiol reductase and disulfide bond isomerase activities, indicating comparability of BjPDI with PDIs in term of enzymatic activities. We also showed that rBjPDI induced bacterial agglutination and exhibited a lectin-like activity capable of binding both bacteria (E. coli and S. aureus) and their signature molecules LPS and LTA. Furthermore, BjPDI could kill S. aureus via inducing membrane depolarization and intracellular ROS production in vitro, and treatment of amphioxus with a blocking anti-PDI antibody in vivo markedly reduced the survival rate of amphioxus following attack by S. aureus. Collectively, our study demonstrates that amphioxus protein disulfide isomerase acts as both an enzyme and an immunocompotent factor, and reports the specific function and mode of action of PDIs in immune responses.

2.
Biochem Biophys Res Commun ; 579: 47-53, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34583195

RESUMO

Diabetic nephropathy (DN) is one of the most serious and major renal complications of diabetes. Previously, Six-transmembrane Protein of Prostate 2 (STAMP2) was reported to contribute to nutritional stress. The purpose of this study is to investigate whether overexpression of STAMP2 attenuates diabetic renal injuries in DN rats. We induced the DN rat model by high-fat diet and low-dose streptozotocin and evaluated the metabolite and urine albumin/creatinine. Recombinant adeno-associated virus vectors were injected for overexpression of STAMP2. Pathophysiologic and ultrastructure features of DN by histochemical stain and transmission electron microscope, autophagy-related proteins and signaling pathway by western blotting were assessed. We found the expression of STAMP2 was decreased and autophagy was blunted in DN rat kidneys. Overexpressing STAMP2 significantly ameliorated metabolic disturbance, insulin resistance, and specifically restoring diabetic renal injury. Furthermore, overexpressing STAMP2 improved the autophagy deficiency in DN rats, as revealed by changes in the expressions of Beclin1, p62, and LC3. Furthermore, STAMP2 overexpressing promoted autophagy by inhibiting the mTOR and activating the AMPK/SIRT1 signaling pathway. Our results suggested that STAMP2 overexpression attenuated renal injuries via upregulating autophagy in DN rats. STAMP2 overexpressing promoted autophagy may been involved with inhibition of the mTOR/ULK1 and activation of the AMPK/SIRT1 signaling pathway.

3.
ACS Chem Neurosci ; 12(18): 3410-3417, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34469110

RESUMO

Adenosine receptor (AR) radiotracers for positron emission tomography (PET) have provided knowledge on the in vivo biodistribution of ARs in the central nervous system (CNS), which is of therapeutic interest for various neuropsychiatric disorders. Additionally, radioligands that can image changes in endogenous adenosine levels in different physiological and pathological conditions are still lacking. The binding of known antagonist adenosine A1 receptor (A1R) radiotracer, [11C]MDPX, failed to be inhibited by elevated endogenous adenosine in a rodent PET study. Since most of the known AR PET radiotracers were antagonists, we propose that an A1R agonist radioligand may possess higher sensitivity to measure changes in endogenous adenosine concentration. Herein, we report our latest findings toward the development of a full agonist adenosine A1 radioligand for PET. Based on a 3,5-dicyanopyridine template, 16 new derivatives were designed and synthesized to optimize both binding affinity and functional activity, resulting in two full agonists (compounds 27 and 29) with single-digit nanomolar affinities and good subtype selectivity (A1/A2A selectivity of ∼1000-fold for compound 27 and 29-fold for compound 29). Rapid O-[11C]methylation provided [11C]27 and [11C]29 in high radiochemical yields and radiochemical purity. However, subsequent brain PET imaging in rodents showed poor brain permeability for both radioligands. An in vivo PET study using knockout mice for MDR 1a/a, BCRP, and MRP1 indicated that these compounds might be substrates for brain efflux pumps. In addition, in silico evaluation using multiparameter optimization identified high molecular weight and high polar surface area as the main molecular descriptors responsible for low brain penetration. These results will provide further insight toward development of full agonist adenosine A1 radioligands and also highly potent CNS A1AR drugs.


Assuntos
Proteínas de Neoplasias , Agonistas do Receptor Purinérgico P1 , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Adenosina , Animais , Camundongos , Tomografia por Emissão de Pósitrons , Distribuição Tecidual
4.
Langmuir ; 37(38): 11281-11291, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34520212

RESUMO

Bulk nanobubbles (NBs) have received considerable attention because of their extensive potential applications, such as in ultrasound imaging and water management. Although multiple types of experimental evidence have supported the existence and stabilization of bulk NBs, the underlying mechanism remains unclear. This study numerically investigates the bulk NB stabilization with molecular dynamics (MD) methods: the all-atom (AA) MD simulation is used for NBs of several nanometers diameter; the coarse-grained (CG) MD simulation is for the NBs of about 100 nm. The NB properties are statistically obtained and analyzed, including the inner density, inner pressure, surface charge, interfacial hydrogen bond (HB), and gaseous diffusion. The results show that the gas inside an NB has ultrahigh density (tens of kilograms per cubic meter). A double-layer surface charge exists on the NB. The inner/outer layer is positively/negatively charged, and the electrostatic stress can counteract part of the surface tension. In addition, the interfacial HB is weakened by the interaction between gas and water molecules, causing less surface tension. The above features are beneficial to NB stabilization. The NB equilibrium radii solved by the interfacial mechanical equilibrium equation agree with the MD results, indicating that this equation can describe the force balance of an NB as small as several nanometers. Besides, supersaturation appears to be necessary for the NB thermodynamic equilibrium. Based on Henry's law and the ideal gas law, the theoretical analysis suggests that the stability of the NB thermodynamic equilibrium is conditional: the number of gas molecules in NBs should be more than half that dissolved in liquid. This study unravels a stabilized bulk NB's properties and discusses the NB equilibrium and stabilization mechanism, which will advance the understanding and application of bulk NBs.

5.
Virol J ; 18(1): 193, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565393

RESUMO

BACKGROUND: Foot-and-mouth disease (FMD) is a devastating animal disease. Anti-non-structural protein (NSP) antibody detection is very important for confirming suspected cases, evaluating the prevalence of infection, certifying animals for trade and controlling the disease. METHODS: In this study, a competitive chemiluminescence immunoassay (3B-cCLIA) was developed for the rapid detection of antibodies against NSPs in different species of livestock animals using the monoclonal antibody (mAb) 9E2 as a competitive antibody that recognizes NSP 3B. RESULTS: The cut-off value (50%), diagnostic sensitivity (Dsn) (97.20%, 95.71%, and 96.15%) and diagnostic specificity (Dsp) (99.51%, 99.43%, and 98.36) of the assay were estimated by testing a panel of known-background sera from swine, cattle and sheep, respectively. The accuracy rate of the 3B-cCLIA was further validated and subsequently compared with that of two commercial diagnostic kits. The early diagnostic results showed that antibodies recognizing NSPs developed later (approximately 1-2 days) than antibodies recognizing structural proteins. Furthermore, anti-NSP antibody presence in animals vaccinated multiple times (false positives), especially cattle and sheep, was confirmed, and the false-positive rate increased with the number of vaccinations. CONCLUSIONS: These results indicate that the 3B-cCLIA is suitable for the rapid detection of antibodies against FMDV NSP 3B in a wide range of species.

6.
Fish Shellfish Immunol ; 118: 147-154, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34487827

RESUMO

Previous studies show that some ribosomal proteins perform immune effector functions via killing bacteria directly. However, it remains largely unknown about other effector functions of ribosomal proteins during a bacterial infection. In this study, we expressed and purified four ribosomal proteins of the amphioxus Branchiostoma japonicum, termed rBjRPS15, rBjRPS18, rBjRPS19 and rBjRPS30-precursor (rBjRPS30P). They all exhibited bactericidal activity against Gram-positive Staphylococcus aureus, and with the exception of rBjRPS19 and rBjRPS30P, were capable of killing Gram-negative Escherichia coli. Importantly, rBjRPS15, rBjRPS19 and rBjRPS30P were able to agglutinate S. aureus in the presence of Mg2+, but none of them could agglutinate E. coli even in the presence of Mg2+ or Ca2+. Moreover, the S. aureus agglutination was achieved by the binding of these three proteins to the peptidoglycan component of the bacterial cell wall. This is the first report showing that some ribosomal proteins possess bacterial agglutinating activity, and these data provide a new angle to the roles of ribosomal proteins in immune defense.

7.
Sci Rep ; 11(1): 16428, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385560

RESUMO

The incidence of kidney stones is increasing in the US population. Oxalate, a major factor for stone formation, is degraded by gut bacteria reducing its intestinal absorption. Intestinal O. formigenes colonization has been associated with a lower risk for recurrent kidney stones in humans. In the current study, we used a clinical trial of the eradication of Helicobacter pylori to assess the effects of an antibiotic course on O. formigenes colonization, urine electrolytes, and the composition of the intestinal microbiome. Of 69 healthy adult subjects recruited, 19 received antibiotics for H. pylori eradication, while 46 were followed as controls. Serial fecal samples were examined for O. formigenes presence and microbiota characteristics. Urine, collected serially fasting and following a standard meal, was tested for oxalate and electrolyte concentrations. O. formigenes prevalence was 50%. Colonization was significantly and persistently suppressed in antibiotic-exposed subjects but remained stable in controls. Urinary pH increased after antibiotics, but urinary oxalate did not differ between the control and treatment groups. In subjects not on antibiotics, the O. formigenes-positive samples had higher alpha-diversity and significantly differed in Beta-diversity from the O. formigenes-negative samples. Specific taxa varied in abundance in relation to urinary oxalate levels. These studies identified significant antibiotic effects on O. formigenes colonization and urinary electrolytes and showed that overall microbiome structure differed in subjects according to O. formigenes presence. Identifying a consortium of bacterial taxa associated with urinary oxalate may provide clues for the primary prevention of kidney stones in healthy adults.

8.
Membranes (Basel) ; 11(8)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34436375

RESUMO

The thorny issue of membrane biofouling in membrane bioreactors (MBR) calls for new effective control measures. Herein, D-amino acid (DAA) was employed to mediate MBR membrane biofouling by inhibiting biofilm information and disintegrating formed biofilm. Different DAA control ways involving membrane property, DAA-adding timing, and DAA-control mode were explored through experiments and the multiple linear regression model and the response surface methodology. The optimized DAA control ways were acquired, involving DAA used as an active agent, and the DAA-adding timing of 4 h cultured before running, as well as both hydrophilic and hydrophobic membrane, resulting in an approximately 40.24% decrease in the membrane biofouling rate in comparison with the conventional MBR. DAA is an efficient membrane biofouling mediating approach for MBR under optimized control ways combination and a facile solution for solving membrane biofouling in actual membrane systems.

9.
Eur J Med Res ; 26(1): 94, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407888

RESUMO

BACKGROUND: The purpose of present study was to explore the mechanism of nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B(PKB/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways after intervention of advanced glycosylation end products (AGEs) on rat bone-marrow stromal cells (BMSCs). METHODS: Prepare and identify AGEs. BMSCs were isolated from 16 SD rats and cultured with different concentration of AGEs. Cell viability was detected by cell counting kit-8 (CCK-8). BMSCs were cultured with AGEs (0.25 mg/ml) for 30 min, 12 h, 24 h, 72 h and 120 h. In addition, BMSCs were cultured with AGEs, AGEs + JNK inhibitor and AGEs + P38 inhibitor for 24 h and 48 h, respectively. Western blotting and RT-PCR were used to determine the protein and mRNA expression levels, respectively. RESULTS: Cell viability of BMSCs was significantly correlated with concentration and effect time of AGEs (P < 0.05), and the most appropriate concentration was 0.25 mg/ml. AGEs stimulation significantly increased the protein expression levels of NF-κB p65, JNK, p38 (P < 0.05), decreased IκB (P < 0.05), but had no effect on the protein expression of Akt in BMSCs (P > 0.05). At the mRNA level, JNK and p38 inhibitors significantly reduced the levels of NF-κB p65, p38 and JNK, increased IκB (P > 0.05), but had no effect on Akt in BMSCs (P > 0.05). At the protein level, JNK and p38 inhibitors notably decreased the expression of NF-κB p65, p38, p-JNK, P-IκB and JNK (P < 0.001), and increased IκB (P < 0.05). CONCLUSION: Advanced glycosylation end products can inhibit the proliferation of bone-marrow stromal cells through activating MAPK pathway.


Assuntos
Células da Medula Óssea/metabolismo , Proliferação de Células , Produtos Finais de Glicação Avançada/metabolismo , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/metabolismo , Animais , Células da Medula Óssea/fisiologia , Células Cultivadas , MAP Quinase Quinase 4/metabolismo , Masculino , Células-Tronco Mesenquimais/fisiologia , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
Cardiol Young ; : 1-5, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34334149

RESUMO

OBJECTIVES: Aortic valve repair in children is still a challenge. The aim of this study was to analyse the surgical results of children with aortic regurgitation who underwent single leaflet reconstruction using the Ozaki procedure in our medical centre. METHODS: A retrospective study was conducted of nine children with aortic regurgitation who received single leaflet reconstruction from May 2017 to September 2019. Paired t-tests and Wilcoxon signed rank tests were used to compare the data at different time points. RESULTS: The median surgical age was 4.7 (3.5, 6.4) years. Eight patients were pre-operatively diagnosed with severe aortic regurgitation, while one had moderate regurgitation. The left ventricles were significantly enlarged, with an average z-score of 3.8. Single leaflet reconstruction was carried out using glutaraldehyde-treated autologous pericardium under the standard Ozaki procedure. The median follow-up was 22 (14, 33) months. There was no post-operative death or re-intervention. One patient had moderate or more aortic regurgitation during the follow-up. The average degree of aortic regurgitation was mild, and the average z-score of the left ventricle decreased to -0.2 in the last follow-up. CONCLUSIONS: Single leaflet reconstruction using the Ozaki procedure was an effective surgical method for treating children with aortic regurgitation in our centre with satisfactory short-term results.

11.
Anim Biotechnol ; : 1-6, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34429028

RESUMO

This paper presented the results on the study of insulin receptor substrate 1 (IRS1) polymorphisms in Chinese black Tibetan sheep. Via DNA direct sequencing, four variations within 3' untranslated region (UTR) of IRS1, including g.9382T > G, g.9569T > G, g.9572C > T and g.9695A > C were detected in the black Tibetan sheep population. Based on the χ2 test, those four loci deviated from Hardy-Weinberg equilibrium (p < 0.05). In g.9569T > G locus, genotype of GG possessed advantage on body weight (p < 0.05). In g.9572C > T locus, individuals with genotype of TT homozygous mutation decreased significantly on body weight, withers height, body length and chest circumference (p < 0.05 or p < 0.01). In g.9695A > C locus, the body weight and chest circumference were also higher in AA carriers than in CC carriers (p < 0.05). Our results provided evidence that polymorphisms in IRS1 were associated with growth efficiency traits by quantitative genetic analysis, and may be used for marker-assisted selection in Chinese indigenous sheep.

12.
J Med Chem ; 64(17): 12525-12536, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34435786

RESUMO

Distinguishing compounds' agonistic or antagonistic behavior would be of great utility for the rational discovery of selective modulators. We synthesized truncated nucleoside derivatives and discovered 6c (Ki = 2.40 nM) as a potent human A3 adenosine receptor (hA3AR) agonist, and subtle chemical modification induced a shift from antagonist to agonist. We elucidated this shift by developing new hA3AR homology models that consider the pharmacological profiles of the ligands. Taken together with molecular dynamics (MD) simulation and three-dimensional (3D) structural network analysis of the receptor-ligand complex, the results indicated that the hydrogen bonding with Thr943.36 and His2727.43 could make a stable interaction between the 3'-amino group with TM3 and TM7, and the corresponding induced-fit effects may play important roles in rendering the agonistic effect. Our results provide a more precise understanding of the compounds' actions at the atomic level and a rationale for the design of new drugs with specific pharmacological profiles.

13.
Front Cardiovasc Med ; 8: 706979, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447791

RESUMO

Objectives: To evaluate the effect of thrombus aspiration (TA) strategy on the outcomes and its interaction with D-dimer levels in patients with ST-segment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (PCI) in "real-world" settings. Materials and Methods: This study included 1,295 patients with STEMI who had undergone primary PCI with or without TA between January 2013 and June 2017. Patients were first divided into a TA+PCI group and a PCI-only group, and the baseline characteristics and long-term mortality between the two groups were analyzed. Furthermore, we studied the effect of TA on the clinical outcomes of patients grouped according to quartiles of respective D-dimer levels. The primary outcome was all-cause mortality, and the secondary outcomes were new-onset heart failure (HF), rehospitalization, re-PCI, and stroke. Results: In the original cohort, there were no significant differences in all-cause mortality between the TA+PCI and PCI-only groups (hazard ratio, 0.789; 95% confidence interval, 0.556-1.120; p = 0.185). After a mean follow-up of 2.5 years, the all-cause mortality rates of patients in the TA + PCI and PCI-only groups were 8.5 and 16.2%, respectively. Additionally, differences between the two groups in terms of the risk of HF, re-PCI, rehospitalization, and stroke were non-significant. However, after dividing into quartiles, as the D-dimer levels increased, the all-cause mortality rate in the PCI group gradually increased (4.3 vs. 6.0 vs. 7.0 vs. 14.7%, p < 0.001), while the death rate in the TA+PCI group did not significantly differ (4.6 vs. 5.0 vs. 4.0 vs. 3.75%, p = 0.85). Besides, in the quartile 3 (Q3) and quartile 4 (Q4) groups, the PCI-only group was associated with a higher risk of all-cause mortality than that of the TA+PCI group (Q3: 4.0 vs. 7.0%, p = 0.029; Q4: 3.75 vs. 14.7%, p < 0.001). Moreover, the multivariate logistic regression analysis demonstrated that TA is inversely associated with the primary outcome in the Q4 group [odds ratio (OR), 0.395; 95% CI, 0.164-0.949; p = 0.038]. Conclusions: The findings of our real-world study express that routine manual TA during PCI in STEMI did not improve clinical outcomes overall. However, patients with STEMI with a higher concentration of D-dimer might benefit from the use of TA during primary PCI. Large-scale studies are recommended to confirm the efficacy of TA.

14.
iScience ; 24(7): 102797, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34355145

RESUMO

We have established experimental systems to assess the effects of early-life exposures to antibiotics on the intestinal microbiota and gene expression in the brain. This model system is highly relevant to human exposure and may be developed into a preclinical model of neurodevelopmental disorders in which the gut-brain axis is perturbed, leading to organizational effects that permanently alter the structure and function of the brain. Exposing newborn mice to low-dose penicillin led to substantial changes in intestinal microbiota population structure and composition. Transcriptomic alterations implicate pathways perturbed in neurodevelopmental and neuropsychiatric disorders. There also were substantial effects on frontal cortex and amygdala gene expression by bioinformatic interrogation, affecting multiple pathways underlying neurodevelopment. Informatic analyses established linkages between specific intestinal microbial populations and the early-life expression of particular affected genes. These studies provide translational models to explore intestinal microbiome roles in the normal and abnormal maturation of the vulnerable central nervous system.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34444200

RESUMO

Contributing to Taijiquan studies, this research uses spatial analysis tools in ArcGIS 10.3 and SPSS 23.0 to map out the spatial distributional pattern of the Taijiquan organizations in London, and then explores factors attributing to the spatial distribution of Taijiquan culture. The result shows that the distribution of Taijiquan organizations in London generally presents a spatial distribution structure of "dense center + sparse periphery"; the spatial distribution is unbalanced, showing a cohesive distribution; the directional distribution tends to be obvious in areas that are proximate to urban traffic arteries and afforestation in London. Through multivariate hierarchical regression analysis, the study explores the influential factors for the spatial distribution of Taijiquan organizations in London. The results show that: population size, economic level, and education level have little influence on the spatial distribution of Taijiquan organizations; however, the population density of people over 65 years old, the accessibility of public service facilities such as green spaces, and public urban traffic has a significant impact on the spatial distribution of Taijiquan organizations.


Assuntos
Parques Recreativos , Tai Ji , Idoso , Humanos , Londres , Organizações , Densidade Demográfica
16.
J Card Surg ; 36(9): 3131-3137, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34212430

RESUMO

AIMS: This study aimed to investigate the safety, feasibility and, availability of perimembranous ventricular septal defect (PmVSD) closure via a left parasternal ultra-minimal trans intercostal incision in children. METHODS AND RESULTS: From January 2015 to January 2019, 131 children with restrictive PmVSDs were enrolled in this study and successfully done in 126 patients (96.18%). PmVSDs were occluded via an ultra-minimal trans intercostal incision (≤1 cm), and the entire occlusive process was guided and monitored by TEE. A pericardium hanging technique was employed without sternal incision. PmVSDs were closed through a short delivery sheath assembled using a concentric occluder device. All patients were followed up for a period ranging from18 months to 24 months. Thirteen patients with PmVSD had aneurysm of membranous septum (AMS). Multistream (≥2) PmVSDs with AMS were found in 11 cases. After the operation, mild residual shunt beside the amplatzer occluder in one patient was found and had self-healing result during the 5-month follow-up period. Five patients transferred to ventricular septal defect repair operation under direct visualization with a cardiopulmonary bypass. One reason was ventricular fibrillation when guidewire passed the PmVSD, another was device dislocation, and others were the guidewire cannot pass through the PmVSD. CONCLUSIONS: PmVSDs closure using a concentric occluder via a left parasternal ultra-minimal trans intercostal incision under TEE guidance is feasible, safe, and effective in children. This approach can be considered as an alternative treatment to open-heart surgery for restrictive PmVSDs.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Comunicação Interventricular , Dispositivo para Oclusão Septal , Cateterismo Cardíaco , Criança , Ecocardiografia Transesofagiana , Comunicação Interventricular/diagnóstico por imagem , Comunicação Interventricular/cirurgia , Humanos , Desenho de Prótese , Esternotomia , Resultado do Tratamento
17.
DNA Cell Biol ; 40(9): 1200-1210, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34227876

RESUMO

In vitro generation of red blood cells has the potential to circumvent shortfalls in the global demand for blood for transfusion applications. However, cell differentiation and proliferation are often regulated by precise changes in gene expression, but the underlying mechanisms and molecular changes remain unclear. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) can be used to evaluate multiple target genes. To make the results more reliable, suitable reference genes should be used to calibrate the error associated with qRT-PCR. In this study, we utilized bioinformatics to screen 3 novel candidate reference genes (calcium and integrin binding family member 2 [CIB2], olfactory receptor family 8 subfamily B member 8 [OR8B8], and zinc finger protein 425 [ZNF425]) along with eight traditional reference genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH], ß-actin [ACTB], 18S RNA, ß2-microglobulin [ß2-MG], peptidylprolyl isomerase A [PPIA], TATA box-binding protein [TBP], hydroxymethylbilane synthase [HMBS], and hypoxanthine phosphoribosyltransferase 1 [HPRT1]). Two software algorithms (geNorm and NormFinder) were used to evaluate the stability of expression of the 11 genes at different stages of erythrocyte development. Comprehensive analysis showed that expression of GAPDH and TBP was the most stable, whereas ZNF425 and OR8B8 were the least suitable candidate genes. These results suggest that appropriate reference genes should be selected before performing gene expression analysis during erythroid differentiation and that GAPDH and TBP are suitable reference genes for gene expression studies on erythropoiesis.


Assuntos
Proteínas de Ligação ao Cálcio/sangue , Eritrócitos/metabolismo , Proteínas Repressoras/sangue , Células-Tronco/metabolismo , Antígenos CD34/metabolismo , Biomarcadores/sangue , Proteínas de Ligação ao Cálcio/metabolismo , Diferenciação Celular , Eritrócitos/citologia , Sangue Fetal/metabolismo , Expressão Gênica , Humanos , Células-Tronco/citologia
18.
Cardiovasc Diabetol ; 20(1): 143, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271936

RESUMO

BACKGROUND: Fibrinogen (FIB) is an independent risk factor for mortality and cardiovascular events in the general population. However, the relationship between FIB and long-term mortality among CAD patients undergoing PCI remains unclear, especially in individuals complicated with diabetes mellitus (DM) or prediabetes (Pre-DM). METHODS: 6,140 patients with CAD undergoing PCI were included in the study and subsequently divided into three groups according to FIB levels (FIB-L, FIB-M, FIB-H). These patients were further grouped by glycemic status [normoglycemia (NG), Pre-DM, DM]. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. RESULTS: FIB was positively associated with hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) in CAD patients with and without DM (P < 0.001). During a median follow-up of 5.1 years (interquartile range 5.0-5.2 years), elevated FIB was significantly associated with long-term all-cause mortality (adjusted HR: 1.86; 95% CI 1.28-2.69; P = 0.001) and cardiac mortality (adjusted HR: 1.82; 95% CI 1.15-2.89; P = 0.011). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause and cardiac mortality compared with NG group (all P < 0.05). When grouped by both FIB levels and glycemic status, diabetic patients with medium and high FIB levels had higher risk of mortality [(adjusted HR: 2.57; 95% CI 1.12-5.89), (adjusted HR: 3.04; 95% CI 1.35-6.82), all P < 0.05]. Notably, prediabetic patients with high FIB also had higher mortality risk (adjusted HR: 2.27; 95% CI 1.01-5.12). CONCLUSIONS: FIB was independently associated with long-term all-cause and cardiac mortality among CAD patients undergoing PCI, especially in those with DM and Pre-DM. FIB test may help to identify high-risk individuals in this specific population.

19.
Front Endocrinol (Lausanne) ; 12: 700349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290672

RESUMO

Background: In euthyroid patients undergoing percutaneous coronary intervention (PCI), it is still unclear whether free triiodothyronine to free thyroxine (FT3/FT4) ratio can predict the recurrence of cardiovascular events (CVEs). We aim to investigate its association with recurrent long-term adverse events in this population. Methods: 3549 euthyroid patients with prior CVEs history undergoing PCI were consecutively enrolled in our study and subsequently divided into three FT3/FT4 ratio tertiles (T1<2.41, n=1170; 2.41≤T2<2.75, n=1198; T3>2.75, n=1181). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, stroke and revascularization. The secondary endpoints were all-cause death and cardiac death. Results: The median follow-up time was 5 years. The incidence of all-cause death, cardiac death and MACCE were significantly higher among patients in the lowest FT3/FT4 tertile (P<0.05). After adjustment of confounding factors, decreased FT3/FT4 ratio was independently associated with an increased risk of all-cause death (HR 1.82, 95% CI 1.13-2.93, P=0.014), cardiac death (HR 1.90, 95% CI 1.04-3.46, P=0.036) and MACCE (HR 1.33, 95% CI 1.10-1.60, P=0.003) which was driven mainly by all-cause death. Conclusions: In euthyroid patients with prior cardiovascular events undergoing PCI, FT3/FT4 ratio might be a potential predictor of all-cause and cardiac mortality. Routine assessment of FT3/FT4 ratio might be a simple and effective tool for risk stratification in this specific patient population.

20.
BMC Cardiovasc Disord ; 21(1): 299, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126921

RESUMO

BACKGROUND: Oral antiplatelet therapy is the cornerstone of treatment for acute myocardial infaction (AMI). However, detailed usage data on oral antiplatelet therapy are lacking. METHODS: Using data from a nationally representative sample of patients with AMI, the detailed usage of oral antiplatelet therapy was analyzed in 40,202 consecutive eligible patients. RESULTS: The proportions of patients with AMI taking loading doses of aspirin and P2Y12 inhibitors were relatively low (62.2% and 63.6%, respectively), whereas approximately 90% of patients received maintenance doses of aspirin, P2Y12 inhibitors, and dual antiplatelet therapy. The proportions of patients taking loading doses of aspirin and P2Y12 inhibitors gradually decreased with age. Male sex, an educational level of at least college, an interval from onset to treatment of < 24 h, and primary PCI use were associated with a higher proportion of patients taking a loading dose of antiplatelet therapy, whereas those receiving conservative treatment had a lower rate of antiplatelet use (all P < 0.05). The proportion of patients taking loading doses of aspirin was highest in the western region, and that of patients taking loading doses of P2Y12 inhibitors was highest in the eastern region (P < 0.05). In addition, 76.7% of patients with ST-elevation MI and 91% of patients with non-ST-elevation MI received 300-mg loading dose of clopidogrel. CONCLUSIONS: The proportion of patients with AMI receiving loading doses of aspirin and P2Y12 inhibitors during hospitalization was relatively low, and this rate was affected by many factors, such as age, sex, educational level, region of residence, and the interval from onset to treatment. The underutilization of guideline-based P2Y12 inhibitors was also problematic. Hence, quality improvement initiatives are needed to enhance adherence to guidelines to improve consistent use of oral antiplatelet therapy. Trial registration The Chinese Acute Myocardial Infarction Registry; Trial registration number: ChiCTR-ONC-12002636; Registered 31 October 2012; http://www.chictr.org.cn/showproj.aspx?proj=6916.


Assuntos
Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Administração Oral , Idoso , Aspirina/efeitos adversos , China/epidemiologia , Clopidogrel/efeitos adversos , Uso de Medicamentos , Terapia Antiplaquetária Dupla , Medicina Baseada em Evidências , Feminino , Disparidades em Assistência à Saúde , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Padrões de Prática Médica , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Sistema de Registros , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Fatores de Tempo , Resultado do Tratamento
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