Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.175
Filtrar
1.
Inflammation ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052541

RESUMO

In early-stage sepsis, glucose metabolism is increased primarily through glycolysis in the inflammatory response of M1 macrophages. Heparin-binding protein (HBP) has been linked to sepsis, which can promote macrophage activation and inflammatory factor release. However, the mechanism by which glucose metabolism regulates the inflammatory response is unclear. We show that HBP contributes to sepsis by modulating the inflammatory response via lactate-dependent glycolysis in macrophages. Peritoneal macrophages from BALB/c mouse were treated with lipopolysaccharide (LPS). The expression of M1-related proinflammatory genes was investigated by PCR array. IL-1ß, iNOS, TNF-α, and IL-6 mRNA expression was determined by qRT-PCR. Intracellular lactate levels were measured using lactate assays. Nuclear factor-kappaB (NF-κB) activity was determined by electrophoretic mobility shift assays (EMSAs). TNF-α levels were measured by qRT-PCR. HBP enhanced inflammatory gene expression in mouse peritoneal macrophages and intracellular lactate accumulation and significantly increased LPS-stimulated NF-κB transcriptional activity and TNF-α expression through lactate. Lactate was essential for the HBP-induced increase in LPS-stimulated TNF-α expression. The critical role of lactate in HBP-induced NF-κB signaling was confirmed, as α-CHCA-mediated (MCT) suppression significantly inhibited NF-κB activity and TNF-α expression. HBP plays an important role in the initial inflammatory reaction, presumably by activating M1 macrophages, increasing lactate levels, and regulating proinflammatory factor release via NF-κB pathway activation.

2.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33097539

RESUMO

Leveraging the endogenous homology-directed repair (HDR) pathway, the CRISPR-Cas9 gene-editing system can be applied to knock in a therapeutic gene at a designated site in the genome, offering a general therapeutic solution for treating genetic diseases such as hemoglobinopathies. Here, a combined supramolecular nanoparticle (SMNP)/supramolecular nanosubstrate-mediated delivery (SNSMD) strategy is used to facilitate CRISPR-Cas9 knockin of the hemoglobin beta (HBB) gene into the adeno-associated virus integration site 1 (AAVS1) safe-harbor site of an engineered K562 3.21 cell line harboring the sickle cell disease mutation. Through stepwise treatments of the two SMNP vectors encapsulating a Cas9•single-guide RNA (sgRNA) complex and an HBB/green fluorescent protein (GFP)-encoding plasmid, CRISPR-Cas9 knockin was successfully achieved via HDR. Last, the HBB/GFP-knockin K562 3.21 cells were introduced into mice via intraperitoneal injection to show their in vivo proliferative potential. This proof-of-concept demonstration paves the way for general gene therapeutic solutions for treating hemoglobinopathies.

3.
Org Lett ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044081

RESUMO

A nickel-catalyzed enantioselective transfer hydrogenation and deuteration of N-sulfonyl imines was developed. Excellent α-selectivity and high deuterium content were achieved by using inexpensive 2-propanol-d8 as a deuterium source. As a highlight, no deuteration of ß-C-H and the remote C-H of N-sulfonyl amines occurred, which is hard to achieve using other imines or by hydrogen isotope exchange with D2O. Mechanism studies indicated a stepwise pathway through the [Ni-D] intermediate.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33087562

RESUMO

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.

5.
Life Sci ; 263: 118571, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058915

RESUMO

Islet beta-cell dysfunction is an important condition leading to the development of diabetes. Numerous studies have found that miRNA regulates islet ß-cell function. In our previous research, the aberrant expression of miR-383 was revealed in type 2 diabetes mellitus (T2DM) serum. Herein, we aimed to assess the function and underlying mechanism of miR-383 in ß-cells through in vitro and in vivo experiments. Using high glucose media, the ß-cell injury was induced and transfected miR-383 overexpression vector to detect cell function in MIN6. Moreover, miR-383 overexpression lentivirus was administrated into high-fat induced diabetes mice to assess the in vivo effect. Results showed that overexpressing miR-383 reversed the cell apoptosis and oxidative stress, induced by high glucose which targets Toll-like receptors (TLR4) and Apolipoprotein C3 (ApoC3) genes. Furthermore, mechanistic studies demonstrated that miR-383 targeted the TLR4 and ApoC3 3' UTR consequently inhibiting TLR4 and ApoC3 expression in MIN6 cells. Besides, overexpression of miR-383 ameliorated hyperglycemia and pancreatic apoptosis in high-fat induced diabetic mice. Conclusively, miR-383 potentially alleviate pancreatic ß-cell injury induced by high glucose and ameliorates high-fat induced diabetes by suppressing TLR4 and ApoC3 expression.

6.
Ann Palliat Med ; 9(5): 3288-3292, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33065784

RESUMO

BACKGROUND: Dysmenorrhea is one of the most common symptoms in gynecology. It refers to people who experience lower abdominal pain, swelling, backache, or another discomfort before and after menstruation or during menstruation, which seriously affects the quality of life and work. Clinically, there are many methods to treat primary dysmenorrhea, among which acupuncture and traditional Chinese medicine (TCM) are beneficial. This work aimed to test the efficacy of acupuncture and TCM in the treatment of primary dysmenorrhea and hope to supply more reliable evidence for clinical treatment. METHODS: We searched articles from the Wanfang database and China National Knowledge Infrastructure and collected the clinical, randomized, or quasi-randomized controlled trials of acupuncture compared with TCM for primary dysmenorrhea. We tested the quality and data of the included studies according to the Cochrane criteria and compiled detailed systematic reviews and meta-analysis. RESULTS: Seven articles (including 492 patients) on acupuncture and TCM for primary dysmenorrhea were included in the systematic review. Seven studies were included in the final analysis, and there was no heterogeneity among the studies (P=0.98, I2=0%). The results showed that the clinical effectiveness of acupuncture was better than TCM (OR: 4.86, 95% CI: 2.84-8.33, Z =5.75, P<0.00001). CONCLUSIONS: The efficacy of acupuncture is superior to TCM in the treatment of primary dysmenorrhea.

7.
Ann Clin Lab Sci ; 50(5): 638-644, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33067209

RESUMO

OBJECTIVE: Tspan8 (tetraspanin 8) plays critical roles in cell adhesion and motility. Recently, Tspan8 overexpression has been found in various tumors. However, its expression status and prognostic significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The objective of the present study was to assess the expression of Tspan8 and its correlation with clinicopathological features in ccRCC. METHODS: Tspan8 expression was detected in 150 cases of ccRCC and matched paracancerous tissues by immunohistochemistry (IHC) and its relevance with prognosis was analyzed. RESULTS: Our data showed that the high-expression rate of Tspan8 in ccRCC tissues was 74.0%, which was significantly higher than those in paracancerous kidney tissues (43.3%, P=0.001). Meanwhile, Tspan8 expression was positively correlated with tumor size and WHO/ISUP grade in ccRCC. Significantly, Kaplan-Meier analysis and log-rank test revealed that Tspan8 higher expression was associated with poorer overall survival (OS) in ccRCC patients (P<0.05). Cox regression analysis further showed that Tspan8 was a significant independent negative prognostic factor for these patients. CONCLUSION: Tspan8 is overexpressed in ccRCC and indicates poor prognosis, suggesting potential roles of Tspan8 in prognostication and targeted therapy.

8.
Environ Sci Technol ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064452

RESUMO

Dissolved Mn(III) species have been recognized as a significant form of Mn in redox transition environments, but a holistic understanding of their geochemical properties still lacks the characterization of their reactivity as reductants. Through using PbO2 as a surrogate oxidant and pyrophosphate (PP) as a model ligand, we evaluated the thermodynamic and kinetic constrains of dissolved Mn(III) oxidation under environmentally relevant pH. Without disproportionation, Mn(III) complexes could be directly oxidized by PbO2 to produce Mn oxides. The reaction rates decreased with increasing PP:Mn(III) ratio and became negligible when the ratio was above a threshold value. Particulate manganite could also be oxidized by PbO2 with detectable production of Pb(II). The favorability of Mn(III) oxidation by PbO2 as a function of the PP:Mn ratio could be predicted by the stability constant of the Mn(III)-PP complex. We developed kinetic models that couple multiple pathways of Mn oxidation by PbO2 to simulate the dynamics of Pb release, loss of dissolved Mn, as well as Mn(III) production and consumption. Beyond the context of Mn geochemistry, the interactions between Pb and various Mn species, including its trivalent forms, may also have important implications to the water quality in lead service lines within distribution systems.

9.
Gene ; : 145201, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035617

RESUMO

Single nucleotide polymorphism (SNP) has recently become one of the ideal genetic markers. SNP refers to the DNA sequence polymorphism caused by double nucleotide variation in the genome, including the conversion or transversion of segmented bases. The synthesis and metabolism of triglycerides are related to the changes of energy in the body of livestock, which in turn affects their growth and development. Studies have shown that MOGAT1 gene plays a role in the route of triglyceride synthesis. PCR-RFLP and agarose gel electrophoresis technology were used to type the SNP site of MOGAT1 gene at g.25940T > C in this study. Association analysis between typing results and growth trait data was detected by SPSS 20.0 software. Results show that MOGAT1 gene was in a low level of heterozygosity in Xianan, Qinchuan and Pinan cattle population (0 < PIC < 0.25), and in middle level of heterozygosity in YL cattle population(0.25 < PIC < 0.5). And genotype 'AA' was dominant gene in Chinese cattle population. In QC and XN cattle, genotype of GG possess advantage on Body weight (P < 0.05); in YL cattle, individuals with genotype of homozygous mutation decreased significantly on Chest depth (P < 0.05). The purpose of this research is to provide theoretical materials for molecular breeding of yellow cattle and to promote the process of improving the growth traits of Chinese local yellow cattle.

10.
Sci Adv ; 6(36)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917617

RESUMO

Polydopamine (PDA) has been increasingly exploited as an advanced functional material, and its emergent light absorption property plays a crucial role in determining various utilizations. However, the rational design and efficient regulation of PDA absorption property remain a challenge due to the complex structure within PDA. In this work, we propose a facile method to regulate the light absorption behaviors of PDA by constructing donor-acceptor pairs within the microstructures through the chemical connections between indoledihydroxy/indolequinone and their oligomers with 2,2,6,6-tetramethylpiperidine-1-oxyl moiety. The detailed structural and spectral analysis, as well as the density functional theory simulation, further confirms the existence of donor-acceptor molecular pair structures, which could decrease the energy bandgap and increase the electron delocalization for enhancing light absorption across a broad spectrum. These rationally designed PDA nanoparticles with tunable absorption properties also show improved total photothermal effect and demonstrate excellent performances in solar desalination.

11.
J Orthop Surg Res ; 15(1): 384, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887611

RESUMO

BACKGROUND: The positional distribution and size of the weight-bearing area of the femoral head in the standing position as well as the direct active surface of joint force can directly affect the result of finite element (FE) stress analysis. However, the division of this area was vague, imprecise, and un-individualized in most studies related to separate FE models of the femur. The purpose of this study was to quantify the positional distribution and size of the weight-bearing area of the femoral head in standing position by a set of simple methods, to realize individualized reconstruction of the proximal femur FE model. METHODS: Five adult volunteers were recruited for an X-ray and CT examination in the same simulated bipedal standing position with a specialized patented device. We extracted these image data, calculated the 2D weight-bearing area on the X-ray image, reconstructed the 3D model of the proximal femur based on CT data, and registered them to realize the 2D weight-bearing area to 3D transformation as the quantified weight-bearing surface. One of the 3D models of the proximal femur was randomly selected for finite element analysis (FEA), and we defined three different loading surfaces and compared their FEA results. RESULTS: A total of 10 weight-bearing surfaces in 5 volunteers were constructed, and they were mainly distributed on the dome and anterolateral of the femoral head with a crescent shape, in the range of 1218.63-1,871.06 mm2. The results of FEA showed that stress magnitude and distribution in proximal femur FE models among three different loading conditions had significant differences, and the loading case with the quantized weight-bearing area was more in accordance with the physical phenomenon of the hip. CONCLUSION: This study confirmed an effective FE modeling method of the proximal femur, which can quantify the weight-bearing area to define a more reasonable load surface setting without increasing the actual modeling difficulty.

12.
Inorg Chem ; 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32862646

RESUMO

Two bismuth(III) halides hybrids with room-temperature phosphorescence (RTP), namely, [BPy]2[Bi2Cl8(bpym)] (1, BPy = N-butylpyridinium) and [EPy]2[Bi2Cl8(bpym)] (2, EPy = N-ethylpyridinium), were synthesized and characterized. Structural comparison reveals that 1 and 2 possess similar anionic zigzaglike chain of [Bi2Cl8(bpym)]n2n-; however, different packing modes of anion/cations and thus different weak interactions. Interestingly, the utilization of pyridinium cations with different length of alkyl chain could tune the RTP behaviors efficiently. The RTP quantum yield (QY) is increased more than 5-fold from 1 to 2 probably due to more rigid structure of 2 arising from the additional H-bond and anion-π interactions, as confirmed by Hirshfeld surfaces analyses and PLATON calculations. Moreover, additional π-π interactions in 1 could stabilize the triplet excitons, leading to an average lifetime of 1 (11.36 ms at 77 K and 1.407 ms at 298 K) being higher than 2 (0.3618 ms at 77 K and 0.07511 ms at 298 K). Density functional theory (DFT) calculations confirm that inorganic moiety to organic ligand charge-transfer (IOCT) is involved in the phosphorescence process. The present work provides a new sight into the design of RTP metal halides through studying the structure-RTP relationship.

13.
J Craniofac Surg ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32969925

RESUMO

OBJECTIVE: This study analyzed the vascular architecture characteristics of high-flow vascular malformations (VMs) in periorbital regions, as well as the treatment and imaging prognosis of occlusion degree of the outflow veins. METHOD: The clinical data of 24 patients with high-flow VMs in periorbital regions treated in our center from 2012 to 2019 were analyzed retrospectively, and the vascular architecture characteristics, treatment methods, and follow-up results were recorded. RESULTS: The vascular architecture of high-flow VMs in periorbital regions which usually contained the intracranial feeding arteries (24/24,100.0%) and intracranial outflow veins (18/24, 75.0%). The average age of first diagnosis was 23 ±â€Š16 years; the average age of treatment was 37 ±â€Š10 years; the median follow-up time was 42.5 months. Twenty-four patients with high-flow VMs in periorbital regions had 58 treatments in all. The imaging cure was achieved in 6 patients by complete occlusion of outflow veins, and no recurrence was found by DSA. Eighteen patients who get incomplete occlusion of outflow veins were given 49 treatments, and 8 patients had imaging recurrence. Seven patients (7/24, 29.2%) had treatment-related complications in all. CONCLUSIONS: Patients with high-flow VMs in periorbital regions are the most complex cases. The prognosis of patients whose outflow veins can be completely occluded is relatively good. The stepwise embolization while preserving organ function is advisable. Nevertheless, the incidence of treatment complications is still high.

14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(8): 704-711, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32958127

RESUMO

Objective To elucidate the mechanisms by which elongation factor Tu GTP binding domain containing 2 (Eftud2) enhances the immune function of murine macrophages by bioinformatics analysis. Methods The bone marrow-derived macrophages (BMDMs) of Eftud2 myeloid cell-specific knockout (MKO) mice (n=10) and wild-type (WT) littermates (n=10) were collected and stimulated by lipopolysaccharide (LPS) (100 ng/mL) for 2 hours. Bioinformatics analysis was conducted to examine the differences in gene expression and mRNA transcription levels. The the differences in gene expression and alternative splicing of mRNA transcription in BMDMs were analyzed by DEGseq and rMATS, respectively. The signaling pathways affected were clarified by Kyoto Encyclopedia of Genes and Genomes (KEGG) classification and enrichment methods. Results Compared with WT counterparts, the expression levels of IL-6, IL-1ß, TNF-α, and the genes related to immune response in MKO BMDMs were down-regulated following LPS stimulation. KEGG pathway analysis showed that the differently expressed genes in BMDMs and alternative splicing mainly affected the signal transduction and immune system-related metabolic pathways, and had a strong correlation with PI3K-AKT signaling pathway. The difference in alternative splicing also existed in ubiquitination and endocytosis. Compared with WT counterparts, there were 232 differences in alternative splicing in MKO BMDMs, among which 125 were skipping exons, accounting for the largest proportion. In addition, the analysis of alternative splicing differences also confirmed the previous experimental results, that is, Eftud2 could participate in the activation of inflammatory signaling pathways by enhancing the alternative splicing of key molecules such as MyD88 in TLR4-NF-κB signaling pathway, thereby augmenting the function of macrophages. Conclusion Eftud2 can promote the release of inflammatory cytokines in BMDMs by regulating gene expression and alternative splicing, and consequently enhance the immune function of macrophages.

15.
Nat Commun ; 11(1): 4489, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895384

RESUMO

We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Vesículas Extracelulares/genética , Neoplasias Hepáticas/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Química Click/instrumentação , Química Click/métodos , Química Computacional , Simulação por Computador , Diagnóstico Diferencial , Dimetilpolisiloxanos/química , Progressão da Doença , Detecção Precoce de Câncer/instrumentação , Feminino , Células Hep G2 , Humanos , Dispositivos Lab-On-A-Chip , Biópsia Líquida/instrumentação , Biópsia Líquida/métodos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pessoa de Meia-Idade , Nanoestruturas/química , Nanofios/química , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa/instrumentação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
16.
Medicine (Baltimore) ; 99(36): e21924, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899026

RESUMO

BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disease that is slowly becoming a global problem. Salvia miltiorrhiza (SM) has a history of thousands of years of use in China. In recent years, SM has been reported to have the effect of improving Alzheimer's disease. However, there is no systematic review of its efficacy and safety yet. Therefore, we propose a systematic review to evaluate the efficacy and safety of SM for AD patients. METHODS: Six databases will be searched: China National Knowledge Infrastructure (CNKI), China Biological Medicine (CBM), China Scientific Journals Database (CSJD), Wanfang database, PubMed, and EMBASE. The information is searched from January 2010 to July 2020. Languages are limited to English and Chinese. The primary outcomes include changes in the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Activities of Daily Living scale (ADL). Additional outcomes include clinical effective rate and adverse event rate. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system will be used to assess the strength of the evidence. RESULTS: This systematic review will evaluate the efficacy and safety of SM in the treatment of Alzheimer's disease. CONCLUSION: This systematic review provides evidence as to whether SM is effective and safe for Alzheimer's disease patients. SYSTEMATIC REVIEW REGISTRATION: INPLASY202070066.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Salvia miltiorrhiza , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
17.
Sci China Life Sci ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32997330

RESUMO

The Y chromosome plays key roles in male fertility and reflects the evolutionary history of paternal lineages. Here, we present a de novo genome assembly of the Hu sheep with the first draft assembly of ovine Y chromosome (oMSY), using nanopore sequencing and Hi-C technologies. The oMSY that we generated spans 10.6 Mb from which 775 Y-SNPs were identified by applying a large panel of whole genome sequences from worldwide sheep and wild Iranian mouflons. Three major paternal lineages (HY1a, HY1b and HY2) were defined across domestic sheep, of which HY2 was newly detected. Surprisingly, HY2 forms a monophyletic clade with the Iranian mouflons and is highly divergent from both HY1a and HY1b. Demographic analysis of Y chromosomes, mitochondrial and nuclear genomes confirmed that HY2 and the maternal counterpart of lineage C represented a distinct wild mouflon population in Iran that diverge from the direct ancestor of domestic sheep, the wild mouflons in Southeastern Anatolia. Our results suggest that wild Iranian mouflons had introgressed into domestic sheep and thereby introduced this Iranian mouflon specific lineage carrying HY2 to both East Asian and Africa sheep populations.

18.
Biochem Biophys Res Commun ; 533(1): 188-194, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-32958245

RESUMO

AIMS: Dahl salt-sensitive (SS) rats develop similar prediabetes lesion characteristics, such as impaired glucose tolerance (IGT), when compared with the salt resistant rat. In this study, we evaluate the risk of high glucose intake during prediabetes and reveal the metabolic pathways relevant to the pathophysiology of prediabetes to diabetes using the SS rat model and compared this with the salt-resistant consomic SS.13BN rat model. METHODS: SS rats were fed with normal chow ±10% glucose solution ad libitum for five weeks. The same experimental treatment was performed on the SS.13BN rats. Metabolites derived from the serum and liver tissue were measured through biochemical and metabolomics analyses. Multivariate, pathway enrichment, and metabolic correlation network analyses were performed based on the metabolomics data. RESULTS: Biochemical analysis revealed that serum triglyceride (TG) significantly increased with a significant decrease in serum total cholesterol (TC) after high glucose intake in the SS rat. Metabolic pathway analysis revealed that high glucose intake interfered with galactose, glyoxylate, and dicarboxylate metabolism, most evidently in the SS rat. Hepatic l-lactic acid content increased in the SS rat after high glucose intake, whereas the opposite was observed in SS.13BN rats. Metabolic correlation network analysis based on serum metabolites revealed that urea and l-valine had higher metabolic centrality in the SS rat. CONCLUSION: Our findings revealed that high glucose intake can significantly stimulate hypertriglyceridemia and reduce serum TC level. The profoundly altered metabolic pathway included galactose, glyoxylate, and dicarboxylate metabolism. l-lactic acid was screened as a biomarker in liver, whereas l-valine and urea were screened as hub metabolites in serum.

19.
Transfus Apher Sci ; : 102899, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32778523

RESUMO

Riboflavin plus UV light pathogen reduction technology (RF-PRT) is an effective method for inactivating donor-derived leukocytes (DDLs) in blood components. Literature data have shown that reactive oxygen species (ROS) increased in lymphocytes after RF-PRT treatment. Sustained high levels of ROS may abolish the endogenous antioxidant system, leading to damage to proteins, lipids, and nucleic acids, resulting in cell apoptosis. Nevertheless, whether riboflavin plus UV light can trigger leukocyte apoptosis remains obscure. In this study, a pool-and-split design, ABO/D-matched lymphocytes treated with RF-PRT or UV light or left untreated. After treatment, the level of ROS and intracellular calcium were measured in samples. Changes in the protein expression of cleaved PARP, Bax, and Bcl-2 and the activities of caspase-3 and caspase-9 were determined by immunoblot analysis or luminometer, respectively. Cell apoptosis was evaluated by flow cytometry. The effect of ROS on apoptosis was assessed. The RF-PRT treatment significantly augmented ROS production, intracellular calcium concentration. The pro-apoptotic proteins expression levels of Bax, but did not the anti-apoptotic protein Bcl-2, were markedly increased after the RF-PRT treatment. Furthermore, the percentage of apoptotic cells was increased in RF-PRT-treated lymphocytes compared to UV-treated cells or untreated cells. Moreover, the inhibition of ROS generation partially neutralized the apoptosis effects of riboflavin plus UV treatment. These findings revealed that RF-PRT-treated lymphocytes significantly increase the proportion of apoptotic cells by promoting ROS generation delineation of the biochemical processes influenced by RF-PRT are a necessary step to provide novel insights into the riboflavin pathogen inactivation technology.

20.
Sci Rep ; 10(1): 13505, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782321

RESUMO

To analyze the association of IL-1ß with recurrence after the first epileptic seizure in ischemic stroke patients and evaluate its predictive value. 238 patients with the first epileptic seizure after ischemic stroke were included in this study. IL-1ß expression levels were detected through quantitative Real-Time PCR. Kaplan-Meier method was used to perform univariate analysis with log-rank test. The variables with P < 0.1 were then included in multivariate analysis. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value. Among all 238 patients, 107 patients (44.96%) had seizure recurrence and 131 patients (55.04%) had no recurrence. Kaplan-Meier analysis showed that high expression of IL-1ß, low age (< 65 years), male, cortical involvement, large lesion size, late onset, severe neurological impairment and partial seizure type were associated with seizure recurrence. Multivariate analysis showed that IL-1ß expression level (hazard ratio 2.057, 95% confidence interval 1.296-3.318) was independently associated with seizure recurrence. The area under ROC curve (AUC) was 0.803 (SE 0.030, 95% confidence interval 0.744-0.862) when IL-1ß expression levels were applied in predicting seizure recurrence. IL-1ß might be a useful biomarker for early discovery of recurrence after the first epileptic seizure in ischemic stroke patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA