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1.
BMC Geriatr ; 21(1): 225, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794800

RESUMO

BACKGROUND: Sepsis is a critical challenge for the older adults as the immune function is less responsive by aging. Although cell numbers seem preserved in the older adults, macrophages present age-related function decline, which including reduced chemokines, phagocytosis, and autophagy. ABT-263, an inhibitor of the anti-apoptotic protein Bcl-2, is reported had a senolytic effect which can selectively clear the senescent cells in vivo and rejuvenate the aged tissues. METHODS: We treated the aged (12-16 months) and young (4-6 months) C57BL/6 mouse with ABT-263, then gave the animals cecal slurry injection to induce sepsis to observe the effect of senolytic compound ABT-263 on the survival rate of sepsis. Additionally, we isolated peritoneal macrophages from the aged mouse to investigate the cell function and molecular mechanism. 3-methyladenine (3-MA), a phosphatidylinositol 3-kinases (PI3K) inhibitor, and rapamycin, an autophagy-enhancer, were used to block or mimic the autophagy, respectively. RT-PCR and Western Blot were used to detect autophagy related gene and protein changes in sepsis. EGFP-expressing E. coli was used as a marker to evaluate the phagocytic ability of macrophages. RESULTS: The results showed ABT-263 treatment improved the survival rate of sepsis in the aged mouse which related to autophagy, while blocking the autophagy can eliminate this effect. It is revealed that ABT-263 enhanced the phagocytic ability of the peritoneal macrophages by increasing the Trem-2 receptor. Additionally, ABT-263 blocked the binding of Bcl-2 to Beclin-1, thus induced Beclin-1-dependent autophagy. CONCLUSION: ABT-263 enhanced the macrophage function in aged mouse by increasing the Trem-2 receptors and inducing a beclin-1-dependent autophagy, consequently, protected the aged mouse from sepsis.

2.
ChemSusChem ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686778

RESUMO

The synthesis of carbamates by electrocatalytic reduction of CO2 is an effective method to realize the utilization of CO2 resources. The development of high-performance electrocatalysts to complete this process more efficiently is of great significance to sustainable development. Owing to their unique structural characteristics, single-atom catalysts are expected to promote the reaction process more efficiently. In this study, an atomically dispersed Cu species on N-doped carbon nanosheet composite material (Cu-N-C) was prepared by metal-organic framework derivatization. Compared with traditional Cu bulk electrodes, the Cu-N-C material has better catalytic performance for the synthesis of methyl N-phenylcarbamate; and the optimized yield reached 71 % at room temperature and normal pressure. The Cu-N-C material has good stability that the catalytic performance does not decrease after repeated use for 10 times. In addition, the Cu-N-C material has good applicability to this catalytic system, and a variety of amines can be smoothly converted into corresponding carbamates.

3.
Proc Natl Acad Sci U S A ; 118(14)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33785595

RESUMO

Autophagy is a catabolic pathway that provides self-nourishment and maintenance of cellular homeostasis. Autophagy is a fundamental cell protection pathway through metabolic recycling of various intracellular cargos and supplying the breakdown products. Here, we report an autophagy function in governing cell protection during cellular response to energy crisis through cell metabolic rewiring. We observe a role of selective type of autophagy in direct activation of cyclic AMP protein kinase A (PKA) and rejuvenation of mitochondrial function. Mechanistically, autophagy selectively degrades the inhibitory subunit RI of PKA holoenzyme through A-kinase-anchoring protein (AKAP) 11. AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA-cAMP response element-binding signaling, mitochondria respiration, and ATP production in accordance with mitochondrial elongation. AKAP11 deficiency inhibits PKA activation and impairs cell survival upon glucose starvation. Our results thus expand the view of autophagy cytoprotection mechanism by demonstrating selective autophagy in RI degradation and PKA activation that fuels the mitochondrial metabolism and confers cell resistance to glucose deprivation implicated in tumor growth.

4.
Huan Jing Ke Xue ; 42(4): 1801-1810, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742815

RESUMO

To explore the pollution characteristics, potential sources, and ecological and health risk of organophosphate eaters (OPEs) in the surface water of Taihu Lake, water samples from 18 surrounding rivers were collected, as well as 11 water samples from Taihu Lake. The concentrations of 13 OPEs in the water were determined using UPLC-MS/MS, and the spatial distribution of the OPEs in surface water of Taihu Lake basin was further analyzed. The results indicate that, in addition to tripropyl phosphate (TPrP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tricresyl phosphate (TCrP), ten OPEs were detected in all the water samples, the total concentration (ΣOPEs) ranged from 152.5 ng·L-1 to 2524 ng·L-1, and the concentration median value was 519.2 ng·L-1. Tri(chloropropyl) phosphate (TCPP) and tri(2-chloroethyl) phosphate (TCEP) were the dominant OPEs, with the concentration ranges of 73.7-1753.9 ng·L-1 (medium value:204.6 ng·L-1) and 43.9-313.5 ng·L-1 (medium value:131.3 ng·L-1), respectively. The ΣOPEs decreased from the northwest region to the southeast, which corresponds to the economic and industrial development. The results of the source identification reveal that the wastewater discharge from electronics and textile enterprises, construction materials, and vehicular and marine traffic emissions may be the principal sources of the OPEs in Taihu Lake. The ecological risk assessment results indicate that only TCPP, tri(dichloropropyl) phosphate (TDCP), and triphenyl phosphate (TPhP) in some sites had a low risk. The health risk assessment reveals that there were no risks based on water intake, but the long-term risk of OPEs to the aquatic ecosystem and surrounding residents still need attention.


Assuntos
Retardadores de Chama , Poluentes Químicos da Água , China , Cromatografia Líquida , Ecossistema , Monitoramento Ambiental , Ésteres , Retardadores de Chama/análise , Lagos , Organofosfatos , Medição de Risco , Rios , Espectrometria de Massas em Tandem , Água , Poluentes Químicos da Água/análise
5.
Front Immunol ; 12: 617163, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33659003

RESUMO

Preclinical and clinical research has demonstrated that inflammation is a critical factor regulating intracerebral hemorrhage (ICH)-induced brain injury. Growing evidence suggests that myeloid cells and lymphocytes have an effect on the pathophysiological processes associated with ICH, such as inflammation, immune responses, perihematomal edema formation, blood-brain barrier (BBB) integrity, and cell death. However, the underlying mechanisms remain largely unknown. We aimed to explore the role immune cells played at different stages of the ICH. To achieve this, novel bioinformatics algorithms were employed to analyze the gene expression profiles and three different analytical tools were utilized to predict the abundances of cell types. In this study, we found that natural killer (NK) cells infiltrated into the brain parenchyma after ICH. Infiltrating NK cells may mediate brain injury through degranulation and recruitment of other cells. Besides, in the acute phase of ICH, monocytes in peripheral blood carried out phagocytosis and secretion of cytokines. On the other hand, in the subacute stage, non-classical monocytes were activated and showed a stronger ability to carry out heme metabolism, wound healing, and antigen processing and presentation. In conclusion, our findings emphasize the significance of intracerebral infiltrating immunocytes in ICH and demonstrate that ICH is a systemic disease affected by peripheral blood. The hub genes identified might be promising therapeutic targets. We also provide a reference on how to use bioinformatics approaches to explore non-neoplastic immune-related diseases.

6.
Sci Rep ; 11(1): 7149, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785787

RESUMO

Yellow leaf disease caused by sugarcane yellow leaf virus (SCYLV) is one of the most prevalent diseases worldwide. In this study, six near-complete genome sequences of SCYLV were determined to be 5775-5881 bp in length. Phylogenetic analysis revealed that the two SCYLV isolates from Réunion Island, France, and four from China were clustered into REU and CUB genotypes, respectively, based on 50 genomic sequences (this study = 6, GenBank = 44). Meanwhile, all 50 isolates were clustered into three phylogroups (G1-G3). Twelve significant recombinant events occurred in intra- and inter-phylogroups between geographical origins and host crops. Most recombinant hotspots were distributed in coat protein read-through protein (RTD), followed by ORF0 (P0) and ORF1 (P1). High genetic divergences of 12.4% for genomic sequences and 6.0-24.9% for individual genes were determined at nucleotide levels. The highest nucleotide diversity (π) was found in P0, followed by P1 and RdRP. In addition, purifying selection was a main factor restricting variability in SCYLV populations. Infrequent gene flow between Africa and the two subpopulations (Asia and America) were found, whereas frequent gene flow between Asia and America subpopulations was observed. Taken together, our findings facilitate understanding of genetic diversity and evolutionary dynamics of SCYLV.

7.
Cancer Med ; 10(7): 2423-2441, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33666372

RESUMO

BACKGROUND: Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR-125b-2-3p, has been identified for predicting chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR-125b-2-3p in advanced CRC under chemotherapy have yet to be elucidated. METHODS: MiR-125b-2-3p expression was detected by real-time PCR (RT-PCR) in CRC tissues. The effects of miR-125b-2-3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR-125b-2-3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on. RESULTS: MiR-125b-2-3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR-125b-2-3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR-125b-2-3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR-125b-2-3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR-125b-2-3p inhibited the proliferation and epithelial-mesenchymal transition (EMT) of CRC induced by lncRNA XIST. CONCLUSIONS: Lower miR-125b-2-3p expression resulted in lower sensitivity of CRC to chemotherapy and was correlated with poorer survival of CRC patients. LncRNA XIST promoted CRC metastasis acting as a ceRNA for miR-125b-2-3p to mediate WEE1 expression. LncRNA XIST-miR-125b-2-3p-WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC.

8.
Biomed Res Int ; 2021: 6643266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748272

RESUMO

Objectives: Whether patent foramen ovale (PFO) closure is effective on migraine is controversial. This article was aimed at assessing the efficacy of PFO closure on migraine based on randomized controlled trials (RCTs) and observational studies. Methods: We searched PubMed, Embase, and Cochrane databases up to October 2020 evaluating PFO closure versus control in patients with migraine, then conducted a meta-analysis of all RCTs and observational studies, respectively. The main outcomes were (1) respond rate: complete cessation of migraine; (2) reduction in the frequency of migraine attacks per month; and (3) reduction in migraine days per month. Results: Seven studies (3 RCTs and 4 observational studies), containing 887 migraine patients, were identified. (1) The respond rate of PFO closure on migraine was significantly higher than control group both in RCT subgroup and observational studies subgroup (OR 3.86, 95% CI 1.35-11.04, P = 0.01 in RCTs; OR 8.28, 95% CI 2.31-29.67, P = 0.001 in observational studies). (2) Reduction in frequency of migraine attacks was higher in PFO closure group compared with control group in the RCT subgroup analysis (mean difference (MD) = 0.57, 95% CI 0.23-0.90, P = 0.0009). (3) Reduction in migraine days was also higher in PFO closure group compared with control group in the RCT subgroup analysis (MD = 1.33, 95% CI 0.35-2.31, P = 0.008). Conclusions: PFO closure might be suitable for migraine patients, especially for migraine with aura, by cessation of migraine headaches or reducing migraine attacks and migraine days.

9.
Insect Biochem Mol Biol ; 132: 103555, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33639242

RESUMO

The oviduct serves as a delivery tube for mature eggs ovulated from ovaries to egg-laying sites. Oviduct secreted components play important roles in ovulation and fertilization in mammals, however, no oviduct secreted protein has been characterized in an insect to date. Here, we identified a gene highly expressed in the lateral oviduct of the adult females in the brown planthopper (BPH), Nilaparvata lugens, the most destructive rice insect pest. Western blotting and immunofluorescence analyses revealed that the gene encodes a protein that is specifically expressed in the lateral oviduct as a component of the gel-like material secreted by the oviduct epithelial cells into the lumen of the swollen part of the lateral oviducts. The protein was tentatively named N. lugens oviduct secreted protein (Nlodsp). RNA interference (RNAi) against NlOdsp transcripts caused a failure of the lateral oviducts to deliver oocytes to the common oviduct that was, by consequence, plugged by 1-2 oocytes. Moreover, although oocytes in the Nlodsp-deficient ovariole were not released to the oviduct, they continued to develop, finally resulting in the presence of several matured oocytes in an ovariole. These defects evidently declined female fecundity. Together, our results demonstrate that NlOdsp plays an essential role in egg transport through the oviduct during ovulation. This work deepens our understanding of insect reproductive system and provides a potential target gene for RNAi-based insect pest control.

10.
J Neuroinflammation ; 18(1): 43, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588866

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH) can induce excessive accumulation of reactive oxygen species (ROS) that may subsequently cause severe white matter injury. The process of oligodendrocyte progenitor cell (OPC) differentiation is orchestrated by microglia and astrocytes, and ROS also drives the activation of microglia and astrocytes. In light of the potent ROS scavenging capacity of ceria nanoparticles (CeNP), we aimed to investigate whether treatment with CeNP ameliorates white matter injury by modulating ROS-induced microglial polarization and astrocyte alteration. METHODS: ICH was induced in vivo by collagenase VII injection. Mice were administered with PLX3397 for depleting microglia. Primary microglia and astrocytes were used for in vitro experiments. Transmission electron microscopy analysis and immunostaining were performed to verify the positive effects of CeNP in remyelination and OPC differentiation. Flow cytometry, real-time polymerase chain reaction, immunofluorescence and western blotting were used to detect microglia polarization, astrocyte alteration, and the underlying molecular mechanisms. RESULTS: CeNP treatment strongly inhibited ROS-induced NF-κB p65 translocation in both microglia and astrocytes, and significantly decreased the expression of M1 microglia and A1 astrocyte. Furthermore, we found that CeNP treatment promoted remyelination and OPC differentiation after ICH, and such effects were alleviated after microglial depletion. Interestingly, we also found that the number of mature oligodendrocytes was moderately increased in ICH + CeNP + PLX3397-treated mice compared to the ICH + vehicle + PLX3397 group. Therefore, astrocytes might participate in the pathophysiological process. The subsequent phagocytosis assay indicated that A1 astrocyte highly expressed C3, which could bind with microglia C3aR and hinder microglial engulfment of myelin debris. This result further replenished the feedback mechanism from astrocytes to microglia. CONCLUSION: The present study reveals a new mechanism in white matter injury after ICH: ICH induces M1 microglia and A1 astrocyte through ROS-induced NF-κB p65 translocation that hinders OPC maturation. Subsequently, A1 astrocytes inhibit microglial phagocytosis of myelin debris via an astrocytic C3-microglial C3aR axis. Polyethylene glycol-CeNP treatment inhibits this pathological process and ultimately promotes remyelination. Such findings enlighten us that astrocytes and microglia should be regarded as a functional unit in future works.

11.
Circ J ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33504712

RESUMO

BACKGROUND: Smoking is an important risk factor of plaque erosion. This study aimed to investigate the predictors of plaque erosion in current and non-current smokers presenting with ST-segment elevation myocardial infarction (STEMI).Methods and Results:A total of 1,320 STEMI patients with culprit plaque rupture or plaque erosion detected by pre-intervention optical coherence tomography were divided into a current smoking group (n=715) and non-current smoking group (n=605). Plaque erosion accounted for 30.8% (220/715) of culprit lesions in the current smokers and 21.2% (128/605) in the non-current smokers. Multivariable analysis showed age <50 years, single-vessel disease and the absence of dyslipidemia were independently associated with plaque erosion rather than plaque rupture, regardless of smoking status. In current smokers, diabetes mellitus (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.10-0.83; P=0.021) was negatively associated with plaque erosion as compared with plaque rupture. In non-current smokers, minimal lumen area (MLA, OR: 1.37; 95% CI: 1.16-1.62; P<0.001) and nearby bifurcation (OR: 3.20; 95% CI: 1.98-5.16; P<0.001) were positively related to plaque erosion, but not plaque rupture. CONCLUSIONS: In patients with STEMI, the presence of diabetes mellitus significantly increased the risk of rupture-based STEMI but may not have reduced the risk of plaque erosion-based STEMI in current smokers. Nearby bifurcation and larger MLA were associated with plaque erosion in non-current smokers.

12.
Biomech Model Mechanobiol ; 20(2): 683-699, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33389275

RESUMO

Previous studies have shown that the rupture properties of an ascending thoracic aortic aneurysm (ATAA) are strongly correlated with the pre-rupture response features. In this work, we present a two-step machine learning method to predict where the rupture is likely to occur in ATAA and what safety reserve the structure may have. The study was carried out using ATAA specimens from 15 patients who underwent surgical intervention. Through inflation test, full-field deformation data and post-rupture images were collected, from which the wall tension and surface strain distributions were computed. The tension-strain data in the pressure range of 9-18 kPa were fitted to a third-order polynomial to characterize the response properties. It is hypothesized that the region where rupture is prone to initiate is associated with a high level of tension buildup. A machine learning method is devised to predict the peak risk region. The predicted regions were found to match the actual rupture sites in 13 samples out of the total 15. In the second step, another machine learning model is utilized to predict the tissue's rupture strength in the peak risk region. Results suggest that the ATAA rupture risk can be reasonably predicted using tension-strain response in the physiological range. This may open a pathway for evaluating the ATAA rupture propensity using information of in vivo response.

13.
Adipocyte ; 10(1): 28-37, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33393852

RESUMO

Obesity is an important public-health problem worldwide. This study aimed to determine effects of porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on adipocytes injuries and explore associated mechanisms. Adipocytes were isolated from SD rats. pLVX-XBP1 (XBP1 over-expression) and pLVX-XBP1-RNAi (silencing XBP1) were structured and transfected into adipocytes. All adipocytes were divided into pLVX-NC, pLVX-XBP1, pLVX-NC+Pg-LPS and pLVX-XBP1+ Pg-LPS group. Oil-Red O staining was employed to identify isolated adipocytes. Quantitative real-time PCR (qRT-PCR) was used to examine gene transcription of IL-6, TNF-α, leptin, adiponectin. Western blotting was used to detect Bax and caspase-3 expression. Adipocytes were successfully isolated and identified with Oil-Red O staining. Both XBP1 mimic and XBP1 RNAi were effectively transfected into adipocytes with higher expressing efficacy. XBP1 over-expression significantly aggravated Pg-LPS induced inflammatory response compared to adipocytes without Pg-LPS treatment (p<0.05). Pg-LPS significantly enhanced leptin and inhibited adiponectin expression by up-regulating XBP1 expression (p<0.05). XBP1 silence significantly alleviated Pg-LPS induced inflammatory response and reduced leptin, enhanced adiponectin expression in Pg-LPS treated adipocytes compared to adipocytes without Pg-LPS treatment (p<0.05). Pg-LPS induced apoptosis of adipocytes by enhancing XBP1 expression and modulating Bcl-2/Bax pathway associated molecules. In conclusion, Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) induces adipocytes injuries through modulating XBP1 expression and initialling mitochondria-mediated apoptosis.

14.
Int J Mol Sci ; 22(2)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33477960

RESUMO

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [11C]PBR28 and [18F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [11C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [18F]flumazenil is a radioligand for GABAA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [11C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [18F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [11C]PBR28 and [18F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.

15.
Sci Rep ; 11(1): 2001, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479417

RESUMO

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complicated maternally inherited disorder lacking of sensitive and specific biomarkers. The objective of this study was to investigate the serum neurofilament light chain (NfL) as a novel biomarker of neurological dysfunction in MELAS. Patients with different status of MELAS were enrolled in this study. The Mini-Mental State Examination (MMSE) was given to the participants to evaluate cognition status. Multiple functional MRI was performed on the participants. Blood samples were collected and the serum NfL concentrations were determined by the single-molecule array technology (Simoa). This study enrolled 23 patients with MELAS, 15 people in the acute attack phase of MELAS and 10 people in the remission phase, including 2 patients in both acute attack and remission phase. Sixteen healthy controls (HCs) were also enrolled. Serum NfL level increased significantly in patients with MELAS. Serum NfL level in the acute attack group (146.73 [120.91-411.31] pg/ml, median [IQR]) was higher than in the remission group (40.31 [19.54-151.05] pg/ml, median [IQR]) and HCs group (7.70 [6.13-9.78] pg/ml, median [IQR]) (p < 0.05). The level of NfL in the remission phase group was higher than in HCs group (p < 0.05). A negative correlation was found between the serum NfL level and MMSE (p = 0.006, r = -0.650). The NfL concentration correlated positively with stroke-like lesion volume in the brain (r = 0.740, p < 0.001). Serum NfL may serve as a novel biomarker for the neurological dysfunction in MELAS patients.

16.
J Atheroscler Thromb ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33455996

RESUMO

AIMS: Recent studies suggested plaque erosion with noncritical stenosis could be treated distinctly from that with critical stenosis, but their morphological features remained largely unknown. The present study aimed to investigate morphological features of eroded plaques with different lumen stenosis using optical coherence tomography (OCT). METHODS: A total of 348 ST-segment elevated myocardial infarction patients with culprit OCT-defined plaque erosion (OCT-erosion) were analyzed. Based on the severity of lumen area stenosis, all patients with OCT-erosions were divided into the following three groups: Group A (area stenosis <50%, n=50); Group B (50% ≤area stenosis <75%, n=146); Group C (area stenosis ≥ 75%, n=152). RESULTS: Compared with patients in Groups A and B, patients in Group C were older (p=0.008) and had higher prevalence of hypertension (p=0.029). Angiographic analysis showed that 72.0% of the eroded plaques in Group A were located in the left anterior descending artery, followed by 67.8% in Group B, and 53.9% in Group C (p=0.039). OCT analysis showed that Group A had the highest prevalence of fibrous plaques (p<0.001) and nearby bifurcation (p=0.036), but the lowest prevalence of lipid-rich plaques (p<0.001), macrophage accumulation (p<0.001), microvessels (p=0.009), cholesterol crystals (p<0.001), and calcification (p=0.023). Multivariable regression analysis showed fibrous plaque (odds ratio [OR]: 3.014, 95% confidence interval [CI]: 1.932-4.702, p<0.001) and nearby bifurcation (OR: 1.750, 95% CI: 1.109-2.761, p=0.016) were independently associated with OCT-erosion with an area stenosis of <75%. CONCLUSIONS: More than half of OCT-erosions presented with <75% area stenosis, having distinct morphological features from those of OCT-erosions with critical stenosis. Fibrous plaque and nearby bifurcation were independently associated with noncritically stenotic OCT-erosion, suggesting that eroded plaques might need individualized treatment.

17.
J Virol ; 95(6)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33408178

RESUMO

Coxsackievirus A5 (CV-A5) has recently emerged as a main hand, foot, and mouth disease (HFMD) pathogen. Following a large-scale vaccination campaign against enterovirus 71 (EV-71) in China, the number of HFMD-associated cases with EV-71 was reduced, especially severe and fatal cases. However, the total number of HFMD cases remains high, as HFMD is also caused by other enterovirus serotypes. A multivalent HFMD vaccine containing 4 or 6 antigens of enterovirus serotypes is urgently needed. A formaldehyde-inactivated CV-A5 vaccine derived from Vero cells was used to inoculate newborn Kunming mice on days 3 and 10. The mice were challenged on day 14 with a mouse-adapted CV-A5 strain at a dose that was lethal for 14-day-old suckling mice. Within 14 days postchallenge, groups of mice immunized with three formulations, empty particles (EPs), full particles (FPs), and a mixture of the EP and FP vaccine candidates, all survived, while 100% of the mock-immunized mice died. Neutralizing antibodies (NtAbs) were detected in the sera of immunized mice, and the NtAb levels were correlated with the survival rate of the challenged mice. The virus loads in organs were reduced, and pathological changes and viral protein expression were weak or not observed in the immunized mice compared with those in alum-inoculated control mice. Another interesting finding was the identification of CV-A5 dense particles (DPs), facilitating morphogenesis study. These results demonstrated that the Vero cell-adapted CV-A5 strain is a promising vaccine candidate and could be used as a multivalent HFMD vaccine component in the future.IMPORTANCE The vaccine candidate strain CV-A5 was produced with a high infectivity titer and a high viral particle yield. Three particle forms, empty particles (EPs), full particles (FPs), and dense particles (DPs), were obtained and characterized after purification. The immunogenicities of EP, FP, and the EP and FP mixture were evaluated in mice. Mouse-adapted CV-A5 was generated as a challenge strain to infect 14-day-old mice. An active immunization challenge mouse model was established to evaluate the efficacy of the inactivated vaccine candidate. This animal model mimics vaccination, similar to immune responses of the vaccinated. The animal model also tests protective efficacy in response to the vaccine against the disease. This work is important for the preparation of multivalent vaccines against HFMD caused by different emerging strains.

18.
J Mech Behav Biomed Mater ; 115: 104284, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33348213

RESUMO

Knowledges of both local stress and strength are needed for a reliable evaluation of the rupture risk for ascending thoracic aortic aneurysm (ATAA). In this study, machine learning is applied to predict the local strength of ATAA tissues based on tension-strain data collected through in vitro inflation tests on tissue samples. Inputs to machine learning models are tension, strain, slope, and curvature values at two points on the low strain region of the tension-strain curve. The models are trained using data from locations where the tissue ruptured, and subsequently applied to data from intact sites to predict the local rupture strength. The predicted strengths are compared with the known strength at rupture sites as well as the highest tension the tissues experienced at the intact sites. A local rupture index, which is the ratio of the end tension to the predicted rupture strength, is computed. The 'hot spots' of the rupture index are found to match the rupture sites better than those of the peak tension. The study suggests that the strength of ATAA tissue could be reliably predicted from early phase response features defined in this work.

19.
Org Lett ; 23(1): 178-182, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33321042

RESUMO

A cobalt-catalyzed direct C-H carbonylative reaction of N-(2-(1H-indol-1-yl)phenyl)picolinamides for the synthesis of (NH)-indolo[1,2-a]quinoxalin-6(5H)-one skeletons has been developed. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source and picolinamide as the traceless directing group, various free (NH)-indolo[1,2-a]quinoxalin-6(5H)-ones were obtained in good yields (up to 88%). Additionally, a series of product derivatizations were demonstrated, and the core fragment of PARP-1 inhibitor C can be readily constructed by this protocol.

20.
Toxicol Lett ; 338: 78-84, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33309996

RESUMO

Amphotericin B (AmB), an effective polyene drug with broad spectrum antifungal activity, is used for serious fungal infections. Liposomal amphotericin B (LAmB) is a lipid dosage form, which has a significantly improved toxicity profile compared with conventional amphotericin B deoxycholate (DAmB). This study focused on verifying the gender differences in the acute toxicity of LAmB and further exploring its causes. Acute toxicity study of LAmB and DAmB were performed in rats, and toxicity responses and mortality of different sexes were observed and recorded. Concentrations of AmB in rat plasma and tissues were determined by a fully validated UPLC-MS/MS assay. The results demonstrated that LAmB showed significant gender differences in acute toxicity, with more severe toxic symptoms and higher mortality for female rats at different doses, but the same differences were not observed for DAmB under the same condition. To explore the cause of differences, toxicokinetic and tissue distribution studies were performed and the results showed that female animals had higher drug exposure, longer half-life and lower plasma clearance compared to male rats, and the drug was mostly distributed in the liver and kidneys, in which female rats displayed a significant higher concentration than that of male rats.


Assuntos
Anfotericina B/toxicidade , Antifúngicos/toxicidade , Testes de Toxicidade Aguda , Anfotericina B/administração & dosagem , Anfotericina B/farmacocinética , Animais , Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Cromatografia Líquida de Alta Pressão , Feminino , Rim/metabolismo , Fígado/metabolismo , Masculino , Ratos Sprague-Dawley , Fatores Sexuais , Espectrometria de Massas em Tandem , Distribuição Tecidual , Toxicocinética
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