Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.031
Filtrar
1.
Parasite ; 27: 19, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32223884

RESUMO

Bovine Theileria are tick-borne protozoan parasites that invade bovine erythrocytes and lymphocytes. Three main bovine Theileria species have been identified in China: T. orientalis, T. sinensis, and T. annulata. To examine the prevalence of bovine theileriosis in Yanbian, a total of 584 bovine blood samples were collected from five localities from 2017 to 2019 and analyzed by PCR. Six pairs of oligonucleotide primers directed against the 18S rRNA gene of Theileria spp., Tams-1 gene of T. annulata, MPSP gene of T. orientalis, and T. sinensis, were used to detect these parasites. A sequence analysis of the amplified genes confirmed that the Theileria species were T. orientalis and T. sinensis, without T. annulata. The overall prevalence of Theileria in cattle was 42.81% (250/584). Out of the 584 samples, 159 (27.23%) and 157 (26.88%) were positive for T. sinensis and T. orientalis, respectively, and the mixed infection rate was 11.30% (66/584). The total prevalence of bovine Theileria species in Helong, Hunchun, Longjing, Yanji, and Dunhua was 66.28%, 49.68%, 23.81%, 28.15%, and 0%, respectively. These results provide epidemiological data for the prevention and control of bovine Theileria species in Yanbian, China.

2.
J Am Coll Cardiol ; 75(8): 901-915, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32130926

RESUMO

BACKGROUND: Recurrent myocardial infarction (MI) is common in patients with coronary artery disease and is associated with high mortality. Long-term reprogramming of myeloid progenitors occurs in response to inflammatory stimuli and alters the organism's response to secondary inflammatory challenges. OBJECTIVES: This study examined the effect of recurrent MI on bone marrow response and cardiac inflammation. METHODS: The investigators developed a surgical mouse model in which 2 subsequent MIs affected different left ventricular regions in the same mouse. Recurrent MI was induced by ligating the left circumflex artery followed by the left anterior descending coronary artery branch. The study characterized the resulting ischemia by whole-heart fluorescent coronary angiography after optical organ clearing and by cardiac magnetic resonance imaging. RESULTS: A first MI-induced bone marrow "memory" via a circulating signal, reducing hematopoietic maintenance factor expression in bone marrow macrophages. This dampened the organism's reaction to subsequent events. Despite a similar extent of injury according to troponin levels, recurrent MI caused reduced emergency hematopoiesis and less leukocytosis than a first MI. Consequently, fewer leukocytes migrated to the ischemic myocardium. The hematopoietic response to lipopolysaccharide was also mitigated after a previous MI. The increase of white blood count in 28 patients was lower after recurrent MI compared with their first MI. CONCLUSIONS: The data suggested that hematopoietic and innate immune responses are shaped by a preceding MI.

3.
Thorac Cancer ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134200

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). While rapid progression (RP) has been proposed as a non-negligible pattern of response to ICIs, its definition and related factors remain unclear. This study aimed to develop a clinical definition of RP and to identify related factors. METHODS: We retrospectively evaluated Chinese patients who had received an ICI as second-line or later treatment for locally advanced or metastatic NSCLC at a single center. We defined RP as radiological progression at the first response assessment (<2 months after starting the ICI), as well as confirmation of progressive disease or cancer-related death occurring at <3 months. The clinical outcomes were compared for patients with RP or non-RP to identify prognostic factors. RESULTS: The study evaluated 74 eligible patients with detailed records regarding their ICI therapy, including 25 patients (33.8%) who had experienced RP. Relative to patients with non-RP, patients with RP had significantly shorter median progression-free survival (1.7 months [95% CI: 1.4-2.0 months] vs. 6.3 months [95% CI 5.2-7.3 months], P < 0.001; hazard ratio: 0.14, 95% CI: 0.08-0.25) and significantly shorter median overall survival (8.2 months [95% CI 3.0-13.4 months] vs. 22.6 months [95% CI 17.0-28.1 months], P < 0.001; hazard ratio: 0.27, 95% CI: 0.15-0.49). Multivariate analysis revealed that RP was independently predicted by the presence of ≥3 metastatic sites (P = 0.039) and a neutrophil-to-lymphocyte ratio of ≥3 (P = 0.044). CONCLUSIONS: Among NSCLC patients, RP was a common response to ICI monotherapy and was associated with dramatically reduced progression-free and overall survival. Care is needed when selecting ICI monotherapy for these patients, especially if they have ≥3 metastatic sites or a neutrophil-to-lymphocyte ratio of ≥3.

4.
Nano Lett ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32155084

RESUMO

Structured light in the subwavelength scale is important for a broad range of applications ranging from lithography to imaging. Of particular importance is the ability to dynamically shift the pattern of the fields, which has led to the development of structured illumination microscopy. Further extension of structured illumination to plasmonic systems has enabled imaging beyond diffraction limit. However, structured illumination usually requires complicated optical setups entailing moving mechanical parts. Here a polarization tunable structured plasmonic field (SPF) is proposed and experimentally demonstrated. The SPF is formed by surface plasmon interference (SPI) generated by a fishbone-shaped metasurface on a thin gold film. Importantly, the SPF can be continuously shifted by merely varying the linear polarization state of an incident beam. The precise control of the fringes of structured illumination and elimination of mechanical control will have great potential in subdiffractional imaging for practical applications.

5.
Clin Lab ; 66(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32162862

RESUMO

BACKGROUND: The score of Dyspnea, Eosinopenia, Consolidation, Acidemia and Atrial Fibrillation (DECAF) can be used to predict the in-hospital mortality of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). It is worth noting that the DECAF score is the first scoring standard combining biomarkers and clinical variables. The application of biomarkers is helpful for improving the accuracy of the scoring system. In recent years, more and more reports and studies paid attentions to procalcitonin (PCT) in respiratory infectious diseases and its clinical value has attracted increasing attention. The study aimed at investigating the effectiveness of the DECAF score combined with PCT in predicting admission of AECOPD patients to intensive care unit (ICU). METHODS: We conducted a retrospective study. We analyzed data from 171 non-immune individuals over the age of 40 in this study. All patients received blood routine measurement and DECAF score calculation on admission. The primary outcome used to assess the probability of an AECOPD patient was who would get a bed in general ward or ICU. Receiver operating characteristic curves (ROC) are used to assess the sensitivity and specificity of PCT, WBC, creatinine, and DECAF scores in predicting the risk of admissions to the ICU of COPD patients. We combined PCT, WBC, and creatinine with DECAF scores, observing the sensitivity and specificity of the different combinations in predicting COPD patients with regard to who should be admitted to ICU. RESULTS: After analyzing the data from 171 patients, we found that the probability of entering the ICU was 21.05% (36/171). The area under curve (AUC) of PCT, WBC, creatinine, and DECAF score in individually predicting the probability of entering the ICU of AECOPD patients were 0.71 (95% CI 0.61 - 0.81), 0.64 (95% CI 0.52 - 0.75), 0.74 (95% CI 0.63 - 0.84), and 0.88 (95% CI 0.81 - 0.94), respectively, with statistically significant differences (p = 0.00). The sensitivities of PCT, WBC, creatinine and DECAF scores were 0.61, 0.61, 0.56, and 0.91, respectively. The specificities of PCT, WBC, creatinine, and DECAF scores were 0.76, 0.67, 0.88 and 0.74, respectively. The AUC of Combination 1 (PCT&DECAF scores), Combination 2 (WBC&DECAF scores), and Combination 3 (creatinine&DECAF scores) for predicting AECOPD patients entering the ICU was 0.92 (95% CI 0.86 - 0.97), 0.89 (95% CI 0.84 - 0.94), and 0.91 (95% CI 0.85 - 0.96), respectively, with statistically significant differences (p = 0.00); the sensitivities were 0.92, 0.86, and 0.94, respectively, and the specificities were 0.97, 0.78, and 0.74, respectively. CONCLUSIONS: Procalcitonin improves the accuracy and sensitivity of the DECAF score in predicting the probability of AECOPD patients entering the ICU, and PCT was superior to other indexes to improve the sensitivity and specificity of the DECAF score.

6.
Thorac Cancer ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32129008

RESUMO

BACKGROUND: The aim of this study was to examine the trends in the mortality rate and years of life lost (YLL) rate of lung cancer in Tianjin, China, during the period from 1999 to 2016. METHODS: Lung cancer death data were obtained from Tianjin residents' all-cause death monitoring system, which covers the whole population of Tianjin. Crude mortality rate, age-standardized mortality rate, truncated rate (35-64 years), YLL and age-standardized YLL rate data were calculated and trends examined. RESULTS: From 1999 to 2016, a total of 93 358 lung cancer deaths were reported in Tianjin, which accounted for 38.0% of all cancer deaths (93 358/245744). The crude mortality rate of lung cancer had increased 58.5% from 1999 (40.15/100000) to 2016 (63.64/100000), average annual percent change (AACP) = 2.9%, P < 0.01. However, the age-standard YLL rate had decreased to 13.3% in 2016 than in 1999, AACP = -0.8%, P < 0.01, with a stable trend in males (AACP = -0.2%), and noticeable decreasing trend in females (AACP = -1.4%). The lung cancer mortality rate (ASRW) in urban areas was higher than that in rural areas in 1999, with a ratio of 1.99:1. However, it was lower in 2016, with the ratio of 0.98:1. For the truncated rate (35-64 years), it had decreased in urban areas compared with rural areas since the year 2013. CONCLUSION: Lung cancer remains the most fatal cancer in Tianjin. However, the age-standard YLL rate of lung cancer has decreased considerably accompanied by a decline in smoking rate years ago, especially in women and people living in urban areas. Considerable attention is therefore needed in the rural areas where cases of lung cancer are still rapidly increasing.

7.
Environ Res ; 184: 108954, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32145546

RESUMO

Environmental factors are one of the important factors affecting the occurrence of lung cancer. However, few studies have been done on the relationship between hot environment and lung cancer. In the present study, we demonstrated that heat stress leads to anchorage-independent proliferation, mitochondrial apoptosis, and autophagy of Beas-2B cells, which are normal lung bronchial epithelial cells. Heat shock protein 27 (HSP27) promoted heat stress-induced anchorage-independent proliferation and autophagy, but suppressed mitochondrial apoptosis, indicating that HSP27 might act as an oncogene in the malignant transformation of lung epithelial cells. We also showed that HSP27 promoted autophagy of these cells under heat stress via autophagy related 7 (ATG7) and ETS Transcription Factor ELK1 (ELK1), a transcription factor of ATG7, under heat stress. In addition, we showed that HSP27 translation could be repressed by microRNA miR-541, and the biological effects of miR-541 were the opposite to HSP27, suggesting that HSP27 is a downstream target of miR-541. In this study, we characterized a new mechanism whereby HSP27 promotes cell transformation during the onset of lung cancer. Our studies provide new insights into the molecular mechanisms underlying the lung carcinogenic effect of heat exposure. Specifically, heat stress promotes translation of HSP27 by inhibiting miR-541 accumulation, ultimately resulting in activation of autophagy, inhibition of mitochondrial apoptotic pathway and malignant transformation of Human Bronchial Epithelial Cells. This study identifies miR-541 as a potential prognostic biomarker or therapeutic target to improve theory of environmental carcinogenesis.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32213315

RESUMO

Macrobrachium rosenbergii is an important cultural species in China and other Southeast Asian countries. However, Enterobacter cloacae infection has caused a great economic loss in M. rosenbergii culture industry. The immune responses of M. rosenbergii to the E. cloacae infection is not fully characterized. To investigate the immune response of M. rosenbergii against E. cloacae, we performed transcriptome analysis of the M. rosenbergii hepatopancreas with and without E. cloacae infection using RNA-seq. After assembly and annotation, 29,731 high quality unigenes were obtained from RNA-seq data. Differential expression analysis revealed the existence of 2498 significantly differently expressed genes (DEGs) at 12 h post infection, with 1365 up-regulated and 1133 down-regulated genes. Among these DEGs, some well-known immune-related genes were up-regulated significantly, including C-type lectin 1, lectin 3, anti-lipopolysaccharide factor 2, Cu/Zn superoxide dismutase and heat shock protein 70. GO analysis demonstrated 24 biological process subcategories, 14 cellular component subcategories, and 12 molecular function subcategories that were enriched among these DEGs, and some DEGs were clustered into immune related subcategories such as immune system process, response to stimulus, biological adhesion, and antioxidant activity. These DEGs were enriched into 216 KEGG pathways including a core set of immune correlated pathways notably in phagosome and lysosome. In addition, 5 up-regulated and 5 down-regulated immune-related DEGs were selected for further validation by quantitative real-time PCR and the results showed consistence with the RNA-seq data. Additionally, the expression level of six selected immune-related genes (ALF2, CLEC1, LEC3, hemocyanin1, HSP70 and SOD) based on the transcriptomic data were monitored at different point of time in hepatopancreas, gill, hemolymph and intestine. Results revealed these immune-related genes were significantly up-regulated in different tissues from 6 to 24 h after E. cloacae infection. Overall, these results provided valuable information for further studying the immune response of M. rosenbergii against E. cloacae infection.

9.
Int J Nanomedicine ; 15: 1809-1821, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214813

RESUMO

Introduction: Because tumor-associated inflammation is a hallmark of cancer treatment, in the present study, sorafenib mesoporous silica nanomatrix (MSNM@SFN) co-administrated with flufenamic acid (FFA, a non-steroidal anti-inflammatory drug (NSAID)) was investigated to enhance the anti-tumor activity of MSNM@SFN. Methods: Metastatic breast tumor 4T1/luc cells and hepatocellular carcinoma HepG2 cells were selected as cell models. The effects of FFA in vitro on cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in 4T1/luc and HepG2 cells were investigated. The in vivo anti-tumor activity of MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) was evaluated in a 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model, respectively. Results: The results indicated that FFA could markedly decrease cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in both 4T1/luc and HepG2 cells. The enhanced anti-tumor activity of MSNM@SFN+FFA compared with that of MSNM@SFN was confirmed in the 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model in vivo, respectively. Discussion: MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) developed in this study is an alternative strategy for improving the therapeutic efficacy of MSNM@SFN via co-administration with NSAIDs.

10.
Sci Total Environ ; 721: 137699, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32179344

RESUMO

Passive remote sensing has been widely used in recent decades to obtain global particulate matter (PM) mass concentration at daytime and under cloud-free condition. In this study, a retrieval method was developed for providing PM (PM10 and PM2.5) mass concentration both at daytime and nighttime using the latest data version (V4.10) from space-borne Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) lidar measurements. The advantage of the method is that PM10 & PM2.5 mass concentrations were obtained for seven aerosol types respectively base on active remote sensing observation at daytime and nighttime, even under cloudy condition. The results show that satellite-based PM mass concentrations are in good agreement with in-situ observations from 1602 ground monitoring sites throughout the world. Moreover, global distributions of PM10 and PM2.5 mass concentration during 2007-2016 were investigated, showing that for Beijing the annual mean PM2.5 mass concentration at nighttime is 11.31% less than those at daytime, however for London is 36.62%. It is suggested that diurnal variations in PM2.5 mass concentration are closely related to human activities. This work provides a reliable high-resolution database for long-term particulate mass concentrations on the global scale, which is of importance to evaluate aerosol impacts on climate, environment as well as ecosystem.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32179515

RESUMO

OBJECTIVES: Abdominal obesity is more closely associated with diabetes than general obesity in adults, however, it is unknown which kind of obesity is more closely associated with abnormal glucose metabolism in children. RESEARCH DESIGN AND METHODS: We recruited 973 children (aged 3.08±1.06) of mothers with prior gestational diabetes mellitus (GDM). Children's height, weight, waist circumstance, fasting glucose and insulin were measured using standardized methods. Logistic regression models were used to assess the single and joint associations of general and abdominal obesity with the risks of hyperglycemia (the upper quartile of fasting glucose), insulin resistance (the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR)), and ß-cell dysfunction (the lower quartile of HOMA-%ß). RESULTS: Compared with normal weight children, children with general overweight/obesity had higher levels of HOMA-IR and HOMA-%ß, higher ORs for hyperglycemia (1.56, 95% CI 1.06 to 2.30) and insulin resistance (3.44, 95% CI 2.32 to 5.09), but a lower OR for ß-cell dysfunction (0.65, 95% CI 0.41 to 1.04). Children with abdominal obesity had an increased risk of insulin resistance (2.54, 95% CI 1.71 to 3.76) but not hyperglycemia and ß-cell dysfunction compared with children with normal waist circumstance. In the joint analyses, general overweight children with and without abdominal obesity had an increased risk of hyperglycemia and insulin resistance compared with normal weight children. CONCLUSIONS: General obesity was more closely associated with abnormal glucose metabolism than abdominal obesity in children of mothers with GDM.

12.
Sci Rep ; 10(1): 4222, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144389

RESUMO

Enzyme-assisted aqueous extraction residue (REAE) has a lower utilization rate as it is the "waste" produced after the enzyme-assisted aqueous extraction (EAE), but its nutritional value is high. To improve the development and utilization of REAE, in this study, cookies were made by adding REAE (0%, 10%, 20%, 30%, 40%, 50%) as a food additive to a small amount of flour. The AOAC method was used to identify the basic components of REAE, analyze its physical and chemical properties, and characterize the cookie structure change in terms of texture, disulfide bond, and thiol content. An in vitro simulation system and sensory evaluation mechanism were established to analyze the bioavailability and impact of quality. The results show that REAE is a potential food additive. With an increase in the REAE content, the cookies become lighter in color, the sweetness and fat content are reduced, the hardness is increased, and the digestibility and glycerin index are reduced. The change in texture is caused by the reduction of disulfide bonds in the dough. The cookies were 'well accepted' with up to 30% REAE. Therefore, the use of the appropriate amount of REAE as a new food additive will reduce the amount of starch added.

13.
J Endocrinol ; 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32208360

RESUMO

Embryo implantation is essential for normal pregnancy. Decidualization is known to facilitate embryo implantation and maintain pregnancy. Uterine stromal cells undergo transformation into decidual cells after embryo attachment to the endometrium. Pyruvate kinase M2 (PKM2) is a rate limiting enzyme in the glycolysis which catalyzes phosphoenolpyruvic acid transforming into pyruvate. However, little is known regarding the role of PKM2 during endometrium decidualization. In this study, PKM2 was found to mainly located in the uterine glandular epithelium and luminal epithelium on day 1 and day 4 of pregnancy and strongly expressed in decidual zone after embryo implantation. And it was dramatically increased with the onset of decidualization. Upon further exploration, it showed that PKM2 was higher expressed at the implantation sites than that at the inter-implantation sites on days 5 to 7 of pregnancy. PKM2 expression was also significantly increased after artificial decidualized both in vivo and in vitro. After PKM2 expression was knocked down by siRNA, the number of embryo implantation sites in mice on day 7 of pregnancy was significantly reduced and the decidualization markers BMP2 and Hoxa10 were also obviously downregulated in vivo and in vitro. Downregulated PKM2 could also compromise cell proliferation in primary endometrial stromal cells and in Ishikawa cells. The migration rate of Ishikawa cells was also obviously suppressed by si-PKM2 according to the wound healing assay. In conclusion, PKM2 might play an important role in decidualization during early pregnancy, and cell proliferation might be one pathway for PKM2 regulated decidualization.

14.
PLoS One ; 15(3): e0230600, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210447

RESUMO

Rice-crab culture is the characteristic rice ecological breeding model used in the Panjin area of Liaohe River Basin, China, and it can improve the ecological environment and create increased economic benefits. From a food perspective, both rice yield and quality, which are closely related to the fertilization mode, should be considered. However, the effect of different fertilization modes on rice quality has not been comprehensively investigated in this co-culture system. This study investigated the effects of three fertilization modes(FP1, FP2, and OPT) divided according to different fertilization types and methods on rice yield and quality, and set up a non-fertilized control group. In the rice-crab culture system, FP2 used fewer fertilizers and had a lower economic cost, and the yield was only slightly less than that of OPT(highest yield) but there was no statistical difference. FP2 elicited the best appearance quality and better cooking and eating quality among all treatment modes. Compared with CK, three fertilization modes significantly increased the protein content in rice and decreased the amylose content, which would lead to the deterioration of rice eating quality. However FP2 had the least protein increase and the least amylose reduction. There was no significant change in crude fat and starch content. Therefore, the FP2 fertilization mode was the best choice for the rice-crab culture system, as it significantly improved rice yield and increased rice quality at a relatively low cost.

15.
Eur Spine J ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32211999

RESUMO

OBJECTIVE: To investigate the relationship between different types of laminectomy extension and spinal cord injury subsequent to acute spinal shorting after 3-column osteotomy in living goat model. METHODS: A total of 18 healthy goats were selected, and a procedure of bivertebral column resections and total laminectomy of T13 and L1 was completed followed by different laminectomy extensions under the somatosensory evoked potential (SSEP) monitoring. The samples were divided into three groups according to types of subsequent laminectomy extension. In the first group (enlarged resection of upper lamina group), laminectomy extension was performed on 10 mm caudal to T12; in the second group (equidistant enlarged resection of upper and lower lamina group), laminectomy extension was performed on 5 mm caudal to T12 and 5 mm cranial to L2 simultaneously; and in the third group (enlarged resection of lower lamina group), laminectomy extension was performed on 10 mm cranial to L2. The SSEP measured after vertebral resection was set as the baseline, and the SSEP decreased by 50% from the baseline amplitude and/or delayed by 10% relative to the baseline peak latency was set as positive results, which indicated spinal cord injury. Spinal column was gradually shortened until the SSEP monitoring just did not show a positive result. The shortened distance (ΔH) and the changed angle of the spinal cord buckling (Δα) were measured in each group. Neurologic function was recorded by the Tarlov scores at 2 days after the surgery. RESULTS: The safe shortening distances of three groups were 38.6 ± 1.2 mm, 41.5 ± 0.7 mm, 43.7 ± 0.8 mm, respectively; the corresponding changed angles of the spinal cord buckling were 62.8 ± 6.9°, 82.8 ± 7.5°, and 98.5 ± 7.0°. Significant differences of ΔH and Δα were found among the three groups by LSD multiple comparison test (P < 0.05). Strong correlation between ΔH and Δα was shown in each group by Pearson's correlation test. CONCLUSIONS: Different laminectomy extensions after 3-column osteotomy have different effects on the prevention of SCI caused by acute spinal shortening. The enlarged resection of lower lamina is superior to equidistant enlarged resection of upper and lower laminas which is superior to enlarged resection of upper lamina in preventing SCI. These slides can be retrieved under Electronic Supplementary Material.

16.
J Neurochem ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32058590

RESUMO

Synaptotagmin-7 (Syt-7) is one of two major calcium sensors for exocytosis in adrenal chromaffin cells, the other being synaptotagmin-1 (Syt-1). Despite a broad appreciation for the importance of Syt-7, questions remain as to its localization, function in mediating discharge of dense core granule cargos, and role in triggering release in response to physiological stimulation. These questions were addressed using two distinct experimental preparations-mouse chromaffin cells lacking endogenous Syt-7 (KO cells) and a reconstituted system employing cell-derived granules expressing either Syt-7 or Syt-1. First, using immunofluorescence imaging and subcellular fractionation, it is shown that Syt-7 is widely distributed in organelles, including dense core granules. Total internal reflection fluorescence (TIRF) imaging demonstrates that the kinetics and probability of granule fusion in Syt-7 KO cells stimulated by a native secretagogue, acetylcholine, are markedly lower than in WT cells. When fusion is observed, fluorescent cargo proteins are discharged more rapidly when only Syt-1 is available to facilitate release. To determine the extent to which the aforementioned results are attributable purely to Syt-7, granules expressing only Syt-7 or Syt-1 were triggered to fuse on planar supported bilayers bearing plasma membrane SNARE proteins. Here, as in cells, Syt-7 confers substantially greater calcium sensitivity to granule fusion than Syt-1 and slows the rate at which cargos are released. Overall, this study demonstrates that by virtue of its high affinity for calcium and effects on fusion pore expansion, Syt-7 plays a central role in regulating secretory output from adrenal chromaffin cells.

17.
Aging (Albany NY) ; 12(3): 2798-2813, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045883

RESUMO

Atherosclerosis is one of the most common clinical cardiovascular disorders. Accumulating evidence indicates that lncRNAs exert critical functions in atherosclerosis; however, their functional roles and regulatory mechanisms remain unclear. In this study, we induced atherosclerotic plaques in three rabbit carotid arteries through an atherogenic diet and balloon injury; three age-matched rabbits were fed normal chow and served as controls. We thoroughly investigated the RNA (mRNA, lncRNA and miRNA) expression profiles in atherosclerotic rabbit carotid models with deep RNA sequencing. We identified several significantly differentially expressed RNAs. The corresponding lncRNA-miRNA-mRNA network was constructed, and the significantly dysregulated network was selected. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that the mRNAs in the network were involved in leukocyte activation, cell proliferation, cell adhesion molecules and cytokine-cytokine receptor interaction. After rigorous screening, we obtained a differentially expressed lncRNA-miRNA-mRNA interaction network associated with atherosclerosis. In the network, XLOC_054118 and XLOC_030217 upregulate the CHI3L1, SOAT, CTSB and CAPG genes by competitively binding to the miRNA ocu-miR-96-5p. XLOC_062719 and XLOC_063297 upregulate CTSS, CTSB and EDNRA genes by competitively binding to the miRNA ocu-miR-185-5p.

19.
Behav Brain Res ; 384: 112544, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32035184

RESUMO

Functional alterations in the subregions of the anterior cingulate cortex (ACC) have been observed in patients with major depressive disorder (MDD). Studies have shown that higher depressive symptoms are associated with altered functional connectivity (FC) in different ACC sub-regions. Suicide is highly prevalent in patients with MDD; however, it is unclear whether suicidal behavior is associated with the FC alterations in the subregions of the ACC in these indibiduals. Seventy-six patients with MDD (41 with and 35 without a history of suicidal behavior) underwent functional magnetic resonance imaging (fMRI) and were assessed using the Hamilton Rating Scale for Depression (HAMD), the Scale for Suicide Ideation (SSI), and the Columbia Scale for Rating of Suicide Severity. We investigated the FC between the ACC subregions and other brain regions in young MDD patients with and without a history of suicidal behavior. The FC in the subregions of the ACC-superior frontal gyrus differed significantly between the two groups. Additionally, the anterior sgACC-right caudate FC and the pgACC-left insula FC were found to be abnormal in the suicidal MDD group. Interestingly, the suicidal ideation score positively correlated with decreased FC in the pgACC-superior frontal gyrus in both groups, but it negatively correlated with increased FC in the anterior sgACC-superior frontal gyrus in the non-suicidal MDD group. Our findings indicate that altered connections of subregions in the ACC may be involved in the neurological mechanisms underlying suicide in young adults with MDD.

20.
Metallomics ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32051986

RESUMO

Guanine-rich DNA sequences can spontaneously fold into four-stranded structures called G-quadruplexes (G4s). G4s have been identified extensively in the promoter regions of several proto-oncogenes, including c-myc, as well as telomeres. G4s have attracted an increasing amount of attention in the field of nanotechnology because of their use as versatile building blocks of DNA-based nanostructures. In this study, we report the self-assembly of c-myc G-quadruplex DNA controlled by a pair of chiral ruthenium(ii) complexes coordinated by 2-(4-phenyacetylenephenyl)-1H-imidazo[4,5f][1,10]phenanthroline (PBEPIP), Λ-[Ru(bpy)2(PBEPIP)](ClO4)2 (Λ-RM0627, bpy = bipyridine) and Δ-[Ru(bpy)2(PBEPIP)](ClO4)2 (Δ-RM0627). Λ-RM0627 could promote the high-order self-assembly of c-myc G-quadruplex DNA into a nanowire structure, whereas Δ-RM0627 could induce DNA condensation into G-quadruplex aggregates. Moreover, in vitro studies on human liver carcinoma HepG2 cells showed that the nanowire of c-myc G-quadruplex DNA promoted by Λ-RM0627 could be localized in the nuclei of cells, whereas the nanoparticle of c-myc G-quadruplex DNA generated by Δ-RM0627 was taken up and localized in the cytoplasm. This study provides examples of the enantioselective self-assembly of G4 DNA molecules controlled by chiral ruthenium(ii) complexes and suggests the potential applications of assembled nanostructures as non-viral DNA vectors for gene therapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA