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1.
J Cell Mol Med ; 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33973365

RESUMO

Abnormal accumulation of lipids and massive deposition of foam cells is a primary event in the pathogenesis of atherosclerosis. Recent studies have demonstrated that autophagy and lysosomal function of atherosclerotic macrophages are impaired, which exacerbates the accumulation of lipid in macrophages and formation of foam cells. Gastrodin, a major active component of Gastrodia elata Bl., has exerted a protective effect on nervous system, but the effect of gastrodin on atherosclerotic vascular disease remains unknown. We aimed to evaluate the effect of gastrodin on autophagy and lysosomal function of foam cells and explored the mechanism underlying gastrodin's effect on the formation of foam cells. In an in vitro foam cell model constructed by incubating macrophages with oxygenized low-density lipoproteins (ox-LDL), our results showed that lysosomal function and autophagy of foam cells were compromised. Gastrodin restored lysosomal function and autophagic activity via the induction of lysosomal biogenesis and autophagy. The restoration of lysosomal function and autophagic activity enhanced cholesterol efflux from macrophages, therefore, reducing lipid accumulation and preventing formation of foam cells. AMP-activated protein kinase (AMPK) was activated by gastrodin to promote phosphorylation and nuclear translocation of forkhead box O1 (FoxO1), subsequently resulting in increased transcription factor EB (TFEB) expression. TFEB was activated by gastrodin to promote lysosomal biogenesis and autophagy. Our study revealed that the effect of gastrodin on foam cell formation and that induction of lysosomal biogenesis and autophagy of foam cells through AMPK-FoxO1-TFEB signalling axis may be a novel therapeutic target of atherosclerosis.

2.
Clin Transl Med ; 11(4): e379, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33931972

RESUMO

BACKGROUND AND AIMS: 4-phenylbutyric acid (4-PBA) is a low molecular weight fatty acid that is used in clinical practice to treat inherited urea cycle disorders. In previous reports, it acted as a chemical chaperone inhibiting endoplasmic reticulum (ER) stress and unfolded protein response signaling. A few studies have suggested its function against hepatic fibrosis in mice models. However, its role in hepatocarcinogenesis remained unknown. METHODS: 4-PBA was administered alone or in combination with diethylnitrosamine to investigate its long-term effect on liver tumorigenesis. The role of 4-PBA in oncogene-induced hepatocellular carcinoma (HCC) mice model using sleeping beauty system co-expressed with hMet and ß-catenin point mutation (S45Y) was also observed. RNA-seq and PCR array were used to screen the pathways and genes involved. In vitro and in vivo studies were conducted to explore the effect of 4-PBA on liver and validate the underlying mechanism. RESULTS: 4-PBA alone didn't cause liver tumor in long term. However, it promoted liver tumorigenesis in HCC mice models via initiation of liver cancer stem cells (LCSCs) through Wnt5b-Fzd5 mediating ß-catenin signaling. Peroxisome proliferator-activated receptors (PPAR)-α induced by 4-PBA was responsible for the activation of ß-catenin signaling. Thus, intervention of PPAR-α reversed 4-PBA-induced initiation of LCSCs and HCC development in vivo. Further study revealed that 4-PBA could not only upregulate the expression of PPAR-α transcriptionally but also enhance its stabilization via protecting it from proteolysis. Moreover, high PPAR-α expression predicted poor prognosis in HCC patients. CONCLUSIONS: 4-PBA could upregulate PPAR-α to initiate LCSCs by activating ß-catenin signaling pathway, promoting HCC at early stage. Therefore, more discretion should be taken to monitor the potential tumor-promoting effect of 4-PBA under HCC-inducing environment.

3.
Oxid Med Cell Longev ; 2021: 5512322, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959215

RESUMO

Ketogenic diet (KD) is popular in diabetic patients but its cardiac safety and efficiency on the heart are unknown. The aim of the present study is to determine the effects and the underlined mechanisms of KD on cardiac function in diabetic cardiomyopathy (DCM). We used db/db mice to model DCM, and different diets (regular or KD) were used. Cardiac function and interstitial fibrosis were determined. T-regulatory cell (Treg) number and functions were evaluated. The effects of ketone body (KB) on fatty acid (FA) and glucose metabolism, mitochondria-associated endoplasmic reticulum membranes (MAMs), and mitochondrial respiration were assessed. The mechanisms via which KB regulated MAMs and Tregs were addressed. KD improved metabolic indices in db/db mice. However, KD impaired cardiac diastolic function and exacerbated ventricular fibrosis. Proportions of circulatory CD4+CD25+Foxp3+ cells in whole blood cells and serum levels of IL-4 and IL-10 were reduced in mice fed with KD. KB suppressed the differentiation to Tregs from naive CD4+ T cells. Cultured medium from KB-treated Tregs synergically activated cardiac fibroblasts. Meanwhile, KB inhibited Treg proliferation and productions of IL-4 and IL-10. Treg MAMs, mitochondrial respiration and respiratory complexes, and FA synthesis and oxidation were all suppressed by KB while glycolytic levels were increased. L-carnitine reversed Treg proliferation and function inhibited by KB. Proportions of ST2L+ cells in Tregs were reduced by KB, as well as the production of ST2L ligand, IL-33. Reinforcement expressions of ST2L in Tregs counteracted the reductions in MAMs, mitochondrial respiration, and Treg proliferations and productions of Treg cytokines IL-4 and IL-10. Therefore, despite the improvement of metabolic indices, KD impaired Treg expansion and function and promoted cardiac fibroblast activation and interstitial fibrosis. This could be mainly mediated by the suppression of MAMs and fatty acid metabolism inhibition via blunting IL-33/ST2L signaling.

4.
J Agric Food Chem ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33945271

RESUMO

In the current work, a series of 1-trifluoromethyl cinnamyl alcohol derivatives were designed and synthesized and their antifungal activities were evaluated. The bioassay result showed that most compounds exhibited excellent antifungal activity in vitro at 10 µg mL-1. Next, photostable and easily synthesized compound 2 with broad-spectrum antifungal activity in vitro was selected as a potential candidate to evaluate its antibacterial and antifungal activities. The EC50 values of compound 2 against eight fungal plant pathogens in vitro ranged from 3.806 to 17.981 µg mL-1; at the same time, compound 2 could effectively control Podosphaera xanthii, Odium heveae Steinm, Puccinia striiformis West, and Puccinia sorghi in pot experiments. In addition, compound 2 exhibited excellent antibacterial activities in vitro and in vivo against Xanthomonas oryzae pv. oryzae. Furthermore, the absorption and translocation of compound 2 in wheat plants were determined by the high-performance liquid chromatography method. The result showed that compound 2 could be translocated acropetally as well as basipetally in wheat plants. Finally, it was found that compound 2 had no cross-resistance with carbendazim, azoxystrobin, and boscalid.

5.
Inorg Chem ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33945276

RESUMO

Materials that demonstrate a multichannel controllable color change in response to external stimuli are fascinating for their potential applications in sensoring and displaying devices. Herein we report a FeII spin-crossover (SCO) compound that exhibits both solvatochromism and thermochromism under an ambient environment. This Hofmann-type compound possesses two different pores where the solvent guests can be removed in a two-step process. Because the loss of solvent guests modifies the spin state of magnetic centers, an unusual yellow-red-yellow two-step color change of crystals was detected. Moreover, because of the strong cooperativity of the spin centers, a dramatic red-to-yellow color change of crystals in response to a minute thermal perturbation around 303 K is triggered by an abrupt spin transition of the metal centers. The multichannel controllable dramatic color change demonstrated in the present compound highlights the sensoring and displaying roles of SCO materials.

7.
Front Immunol ; 12: 650424, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33927720

RESUMO

Chronic renal graft dysfunction (CAD) is caused by multiple factors, including glomerular sclerosis, inflammation, interstitial fibrosis and tubular atrophy (IF/TA). However, the most prominent elements of CAD are IF/TA. Our studies have confirmed that endothelial-mesenchymal transition (EndMT) is an important source to allograft IF/TA. The characteristic of EndMT is the loss of endothelial marker and the acquisition of mesenchymal or fibroblastic phenotypes. Autophagy is an intracellular degradation pathway that is regulated by autophagy-related proteins and plays a vital role in many fibrotic conditions. However, whether or not autophagy contributes to fibrosis of renal allograft and how such mechanism occurs still remains unclear. Autophagy related 16 like gene (ATG16L) is a critical autophagy-related gene (ARG) necessary for autophagosome formation. Here, we first analyzed kidney transplant patient tissues from Gene Expression Omnibus (GEO) datasets and 60 transplant patients from our center. Recipients with stable kidney function were defined as non-CAD group and all patients in CAD group were histopathologically diagnosed with CAD. Results showed that ATG16L, as one significant differential ARG, was less expressed in CAD group compared to the non-CAD group. Furthermore, we found there were less autophagosomes and autolysosomes in transplanted kidneys of CAD patients, and downregulation of autophagy is a poor prognostic factor. In vitro, we found out that the knockdown of ATG16L enhanced the process of EndMT in human renal glomerular endothelial cells (HRGECs). In vivo, the changes of EndMT and autophagic flux were then detected in rat renal transplant models of CAD. We demonstrated the occurrence of EndMT, and indicated that abundance of ATG16L was accompanied by the dynamic autophagic flux change along different stages of kidney transplantation. Mechanistically, knockdown of ATG16L, specifically in endothelial cells, reduced of NF-κB degradation and excreted inflammatory cytokines (IL-1ß, IL-6 and TNF-α), which could facilitate EndMT. In conclusion, ATG16L-dependent autophagic flux causing by transplant showed progressive loss increase over time. Inflammatory cytokines from this process promoted EndMT, thereby leading to progression of CAD. ATG16L served as a negative regulator of EndMT and development of renal graft fibrosis, and autophagy can be explored as a potential therapeutic target for chronic renal graft dysfunction.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33655479

RESUMO

Models that evaluate the potential geographic distribution of species can be used with a variety of important applications in conservation biology. Osmanthus fragrans has high ornamental, culinary, and medicinal value, and is widely used in landscaping. However, its preferred habitat and the environmental factors that determine its distribution remain largely unknown; the environmental factors that shape its suitability also require analysis. Based on 89 occurrence records and 30 environmental variables, this study constructed Maxent models for current as well as future appropriate habitats for O. fragrans. The results indicate that UV-B seasonality (19.1%), precipitation seasonality (18.8%), annual temperature range (13.1%), and mean diurnal temperature range (12.5%) were the most important factors used for interpreting the environmental demands for this species. Highly appropriate habitats for O. fragrans were mainly distributed in southwestern Jiangsu, southern Anhui, Shanghai, Zhejiang, Fujian, northern Guangdong, Guangxi, southern Hunan, southern Hubei, Sichuan, and Taiwan. Under climate change scenarios, the spatial extent of the area of suitable distribution will decrease, and the distribution center of O. fragrans will shift to the southwest. The results of this study will help land managers to avoid blindly introducing this species into inappropriate habitat while improving O. fragrans yield and quality.

10.
Lung Cancer ; 155: 87-93, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33756357

RESUMO

OBJECTIVES: Inconsistent findings have been reported on the link between dietary carbohydrates and lung cancer. This study aims to comprehensively evaluate the role of dietary carbohydrates on lung cancer risk. MATERIALS AND METHODS: The prospective study is based on the PLCO trial, which recruited 113,096 eligible participants across the United States. Participants had to have completed baseline and diet history questionnaires. The incidence of lung cancer was acquired through self-report and medical record follow-up. A multivariable logistic model adjusted for confounders was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of dietary carbohydrates, fiber, whole grains, glycemic index (GI) and glycemic load (GL) for lung cancer. Similar methods were applied in analyzing the carbohydrates and fiber from different food sources. Multinomial logistic models were used for sensitivity analysis with lung cancer subtypes as outcomes. RESULTS: Dietary carbohydrates and GL were inversely associated with lung cancer incidence in the PLCO population. Among various carbohydrates, 30-g daily consumption of dietary fiber was related to a lower risk of lung cancer (fourth vs first quartile OR: 0.62, 95 % CI: 0.54-0.72) compared with 8.8-g. Furthermore, consuming whole grains 2.3 servings per day as opposed to 0.3 servings per day was associated with a lower risk of lung cancer (OR: 0.73, 95 % CI: 0.64-0.83). A higher risk of lung cancer was seen for the consumption of high-GI food (OR: 1.19, 95 % CI: 1.05-1.35) and refined carbohydrates from soft drinks (OR: 1.23, 95 % CI: 1.04-1.46). CONCLUSION: Carbohydrates and fiber from fruits, vegetables and whole grains are associated with lower lung cancer risk. Refined carbohydrates from processed food, such as soft drinks, appear to increase risk.

11.
J Environ Manage ; 288: 112370, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33761332

RESUMO

Central North China Plain (NCP) is one of the most important source region of air pollutants over the Beijing-Tianjin-Hebei (BTH) region. The national government has issued abatement measures to improve the air quality in this area from 2017. To examine the effects of control measures, observational analysis on PM2.5 characteristics was performed in a city of central NCP during 2017-2019 to investigate the variation in mass concentration, chemical composition, and emission source of PM2.5. Annual PM2.5 concentration significantly reduced by 16% from 2017 to 2019, implying substantial improvements in air quality. PM2.5 enriched in autumn-winter seasons was dominated by SNA (sum of sulfate, nitrate and ammonium; ~38%), followed by organic carbon matters (OM; ~24%) and fine soil (FS; ~12%). This chemical composition was different from that in a megacity in NCP (Beijing) where OM accounted for a comparable fraction to SNA. Approximately half of SNA was attributed to nitrate, indicating that SNA changed from sulfate-driven to nitrate-driven, and the considerable effects of coal combustion cutoff, in which sulfate was concentrated. Decreased mass fraction of SNA and increased OM fraction in PM2.5 were observed in 2018-2019 partly contributed to the decrease in PM2.5. A progressive increase in the contribution of heterogeneous formed SNA whilst a decrease in OM was observed as the pollution elevated from clean to heavily polluted. Six sources (soil dust, biomass burning, secondary emission, road traffic, coal combustion and industry) were identified by the Positive Matrix Factorization (PMF) model in both years and dominated by secondary aerosols, respectively contributing 39% and 41% to PM2.5. The decreasing concentrations (with reductions of 17%-61%) of the secondary source, coal combustion, soil dust and biomass burning largely accounted for the reduction in PM2.5, as a consequence of the recent abatement measures. By contrast, contributions of vehicle-related emissions, similar to the increasing contribution of vehicles at sites in NCP after 2013, should receive increased attention.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , Pequim , China , Cidades , Monitoramento Ambiental , Material Particulado/análise , Estações do Ano , Emissões de Veículos/análise
12.
Artigo em Inglês | MEDLINE | ID: mdl-33687848

RESUMO

Due to the movement expressiveness and privacy assurance of human skeleton data, 3D skeleton-based action inference is becoming popular in healthcare applications. These scenarios call for more advanced performance in application-specific algorithms and efficient hardware support. Warnings on health emergencies sensitive to response speed require low latency output and action early detection capabilities. Medical monitoring that works in an always-on edge platform needs the system processor to have extreme energy efficiency. Therefore, in this paper, we propose the MC-LSTM, a functional and versatile 3D skeleton-based action detection system, for the above demands. Our system achieves state-of-the-art accuracy on trimmed and untrimmed cases of general-purpose and medical-specific datasets with early-detection features. Further, the MC-LSTM accelerator supports parallel inference on up to 64 input channels. The implementation on Xilinx ZCU104 reaches a throughput of 18658 Frames-Per-Second (FPS) and an inference latency of 3.5ms with the batch size of 64. Accordingly, the power consumption is 3.6W for the whole FPGA+ARM system, which is 37.8x and 10.4x more energy-efficient than the high-end Titan X GPU and i7-9700 CPU, respectively. Meanwhile, our accelerator also keeps a 4~5x energy efficiency advantage against the low-power high-performance Firefly-RK3399 board carrying an ARM Cortex-A72+A53 CPU. We further synthesize an 8-bit quantized version on the same hardware, providing a 48.8% increase in energy efficiency under the same throughput.

13.
Oxid Med Cell Longev ; 2021: 5545261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763166

RESUMO

Mitochondrial dysfunction has been suggested to be the key factor in the development and progression of cardiac hypertrophy. The onset of mitochondrial dysfunction and the mechanisms underlying the development of cardiac hypertrophy (CH) are incompletely understood. The present study is based on the use of multiple bioinformatics analyses for the organization and analysis of scRNA-seq and microarray datasets from a transverse aortic constriction (TAC) model to examine the potential role of mitochondrial dysfunction in the pathophysiology of CH. The results showed that NADH:ubiquinone oxidoreductase core subunit S1- (Ndufs1-) dependent mitochondrial dysfunction plays a key role in pressure overload-induced CH. Furthermore, in vivo animal studies using a TAC mouse model of CH showed that Ndufs1 expression was significantly downregulated in hypertrophic heart tissue compared to that in normal controls. In an in vitro model of angiotensin II- (Ang II-) induced cardiomyocyte hypertrophy, Ang II treatment significantly downregulated the expression of Ndufs1 in cardiomyocytes. In vitro mechanistic studies showed that Ndufs1 knockdown induced CH; decreased the mitochondrial DNA content, mitochondrial membrane potential (MMP), and mitochondrial mass; and increased the production of mitochondrial reactive oxygen species (ROS) in cardiomyocytes. On the other hand, Ang II treatment upregulated the expression levels of atrial natriuretic peptide, brain natriuretic peptide, and myosin heavy chain beta; decreased the mitochondrial DNA content, MMP, and mitochondrial mass; and increased mitochondrial ROS production in cardiomyocytes. The Ang II-mediated effects were significantly attenuated by overexpression of Ndufs1 in rat cardiomyocytes. In conclusion, our results demonstrate downregulation of Ndufs1 in hypertrophic heart tissue, and the results of mechanistic studies suggest that Ndufs1 deficiency may cause mitochondrial dysfunction in cardiomyocytes, which may be associated with the development and progression of CH.

14.
Front Immunol ; 12: 618737, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732243

RESUMO

Background: Costimulatory blockade provides new therapeutic opportunities for ensuring the long-term survival of kidney grafts. The adoption of the novel immunosuppressant Belatacept has been limited, partly due to concerns regarding higher rates and grades of acute rejection in clinical trials. In this study, we hypothesized that a combined therapy, Belatacept combined with BTLA overexpression, may effectively attenuate acute rejection after kidney transplantation. Materials and Methods: The rat kidney transplantation model was used to investigate graft rejection in single and combined therapy. Graft function was analyzed by detecting serum creatinine. Pathological staining was used to observe histological changes in grafts. The expression of T cells was observed by immunohistochemistry and flow cytometry. In vitro, we constructed an antigen-stimulated immune response by mixed lymphocyte culture, treated with or without Belatacept and BTLA-overexpression adenovirus, to observe the proliferation of receptor cells and the expression of cytokines. In addition, western blot and qRT-PCR analyses were performed to evaluate the expression of CTLA-4 and BTLA at various time points during the immune response. Results: In rat models, combined therapy reduced the serum creatinine levels and prolonged graft survival compared to single therapy and control groups. Mixed acute rejection was shown in the allogeneic group and inhibited by combination treatment. Belatacept reduced the production of DSA and the deposition of C4d in grafts. Belatacept combined with BTLA overexpression downregulated the secretion of IL-2 and IFN-γ, as well as increasing IL-4 and IL-10 expression. We also found that Belatacept combined with BTLA overexpression inhibited the proliferation of spleen lymphocytes. The duration of the elevated expression levels of CTLA-4 and BTLA differentially affected the immune response. Conclusion: Belatacept combined with BTLA overexpression attenuated acute rejection after kidney transplantation and prolonged kidney graft survival, which suggests a new approach for the optimization of early immunosuppression after kidney transplantation.

15.
Oxid Med Cell Longev ; 2021: 5590855, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777314

RESUMO

Atherosclerosis (AS) is one of the most serious and common cardiovascular diseases affecting human health. AS is featured by the accumulation of plaques in vessel walls. The pathophysiology of AS is relevant in the low-density lipoprotein (LDL) uptake by macrophages, as well as the conversion of macrophages to foam cells. However, the mechanisms about how macrophages regulate AS have not been fully elucidated. In this study, we aimed to illuminate the roles of ZBTB20 and to excavate the underlying regulative mechanisms of ZBTB20 in AS. The microarray analysis revealed that ZBTB20 was a hub gene in the oxidative stress and inflammatory responses induced by oxidized LDL (ox-LDL) in AS. Correspondingly, our validation studies showed that ZBTB20 increased in either the human atherosclerotic lesion or the ox-LDL-stimulated macrophages. Moreover, the knockdown of ZBTB20 decreased M1 polarization, suppressed the proinflammatory factors, inhibited mitochondrial fission, and reduced the oxidative stress level of macrophages induced by ox-LDL. The mechanistic studies revealed that the ZBTB20 knockdown suppressed NF-κB/MAPK activation and attenuated the mitochondrial fission possibly via regulating the nucleus translocation of NRF2, a pivotal transcription factor on redox homeostasis. Our in vivo studies showed that the sh-ZBTB20 adenovirus injection could reduce the progression of AS in apolipoprotein E-deficient (ApoE-/-) mice. All in all, these results suggested that ZBTB20 positively regulated the oxidative stress level, mitochondrial fission, and inflammatory responses of macrophages induced by ox-LDL, and the knockdown of ZBTB20 could attenuate the development of AS in ApoE-/- mice.

17.
Biochem Biophys Res Commun ; 545: 20-26, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33535102

RESUMO

Atherosclerotic cardiovascular disease is the major cause of death worldwide. Low shear stress plays key roles on the initiation and progression of atherosclerosis (As). However, its underlying mechanism remains unclear. In this study, the effect of low shear stress on endothelial mesenchymal transformation (EndMT) and its underlying mechanism were explored. Results showed that in cultured human umbilical vein endothelial cells, low shear stress down-regulated the expression of TET2 and promoted EndMT. Loss of TET2 promoted EndMT with the Wnt/ß-catenin signaling pathway. The enhancement in EndMT induced by low shear stress was attenuated by TET2 overexpression. In apoE-/- mice subjected to carotid artery local ligation, the EndMT and atherosclerotic lesions induced by low shear stress was attenuated by TET2 overexpression. Taken together, low shear stress promoted EndMT through the down-regulation of TET2, indicating that intervention with EndMT or the up-regulation of TET2 might be an alternative strategy for preventing As.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Animais , Aterosclerose/etiologia , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Knockout para ApoE , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/genética , Estresse Mecânico , Regulação para Cima , Via de Sinalização Wnt
18.
Int J Mol Med ; 47(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33576442

RESUMO

The present study aimed to explore the role and mechanisms of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the oxidized low­density lipoprotein (oxLDL)­induced pyroptosis of vascular endothelial cells. For this purpose, human umbilical vein endothelial cells (HUVECs) were incubated with oxLDL (100 µg/ml) for 24 h to induce pyroptosis, which was detected using PI/hoechst33342 double staining. The expression of pyroptosis­associated molecules was measured by western blot analysis and RT­qPCR. Reactive oxygen species (ROS) and membrane potential were examined through ROS probe and JC­1 staining, respectively. PCSK9 and mitochondrial ubiquinol­cytochrome c reductase core protein 1 (UQCRC1) protein were knocked down by small interfering RNA (siRNA). PCSK9 was overexpressed by lentivirus. The results revealed that oxLDL induced HUVEC injury, pyroptosis and inflammatory factor release, and upregulated the expression of PCSK9 protein in the HUVECs in a concentration­dependent manner. The silencing of PCSK9 expression with siRNA suppressed the oxLDL­induced damage to HUVECs, the release of inflammatory substances and the occurrence of pyroptosis. In addition, oxLDL inhibited UQCRC1 expression, promoted mitochondrial membrane potential collapse and damaged mitochondrial function; however, these processes were reversed by the silencing of PCSK9. PCSK9 overexpression induced the pyroptosis of HUVECs, the generation of ROS and the disorder of mitochondrial function by inhibiting UQCRC1. Therefore, PCSK9 mediates the oxLDL­induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway.

19.
BMC Genomics ; 22(1): 94, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522906

RESUMO

BACKGROUND: Paeonia lactiflora 'Hangshao' is widely cultivated in China as a traditional Chinese medicine 'Radix Paeoniae Alba'. Due to the abundant unsaturated fatty acids in its seed, it can also be regarded as a new oilseed plant. However, the process of the biosynthesis of unsaturated fatty acids in it has remained unknown. Therefore, transcriptome analysis is helpful to better understand the underlying molecular mechanisms. RESULTS: Five main fatty acids were detected, including stearic acid, palmitic acid, oleic acid, linoleic acid and α-linolenic acid, and their absolute contents first increased and then decreased during seed development. A total of 150,156 unigenes were obtained by transcriptome sequencing. There were 15,005 unigenes annotated in the seven functional databases, including NR, NT, GO, KOG, KEGG, Swiss-Prot and InterPro. Based on the KEGG database, 1766 unigenes were annotated in the lipid metabolism. There were 4635, 12,304, and 18,291 DEGs in Group I (60 vs 30 DAF), Group II (90 vs 60 DAF) and Group III (90 vs 30 DAF), respectively. A total of 1480 DEGs were detected in the intersection of the three groups. In 14 KEGG pathways of lipid metabolism, 503 DEGs were found, belonging to 111 enzymes. We screened out 123 DEGs involved in fatty acid biosynthesis (39 DEGs), fatty acid elongation (33 DEGs), biosynthesis of unsaturated fatty acid (24 DEGs), TAG assembly (17 DEGs) and lipid storage (10 DEGs). Furthermore, qRT-PCR was used to analyze the expression patterns of 16 genes, including BBCP, BC, MCAT, KASIII, KASII, FATA, FATB, KCR, SAD, FAD2, FAD3, FAD7, GPAT, DGAT, OLE and CLO, most of which showed the highest expression at 45 DAF, except for DGAT, OLE and CLO, which showed the highest expression at 75 DAF. CONCLUSIONS: We predicted that MCAT, KASIII, FATA, SAD, FAD2, FAD3, DGAT and OLE were the key genes in the unsaturated fatty acid biosynthesis and oil accumulation in herbaceous peony seed. This study provides the first comprehensive genomic resources characterizing herbaceous peony seed gene expression at the transcriptional level. These data lay the foundation for elucidating the molecular mechanisms of fatty acid biosynthesis and oil accumulation for herbaceous peony.

20.
Biomater Sci ; 9(5): 1609-1626, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33459311

RESUMO

Intricately structured mesoporous organosilica nanoparticles (IMONs) are being increasingly studied from their synthesis strategies to their use in biomedical applications, because of their distinctive hierarchical structures, excellent physicochemical features and satisfactory biological properties. This minireview is the first to summarize recently developed IMONs, including yolk-shell-structured nanoparticles, multi-shelled hollow spheres, deformable nanocapsules, Janus nanostructures and virus-like bionic-structured nanocarriers, and describe the corresponding formation mechanisms and recent evolution of the strategies used to synthesize these kinds of IMONs. Structure-dependent biomedical applications, such as multidrug delivery, bioimaging, synergistic therapy and biocatalysis, are also discussed. Finally, we provide an outlook for IMONs ranging from their structural control to synthesis strategies and ending with their use in biomedical applications.

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