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1.
World J Pediatr ; 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059960

RESUMO

BACKGROUND: Primary vesicoureteral reflux (VUR) is a common congenital anomaly of the kidney and urinary tract (CAKUT) in childhood. The present study identified the possible genetic contributions to primary VUR in children. METHODS: Patients with primary VUR were enrolled and analysed based on a national multi-center registration network (Chinese Children Genetic Kidney Disease Database, CCGKDD) that covered 23 different provinces/regions in China from 2014 to 2019. Genetic causes were sought using whole-exome sequencing (WES) or targeted-exome sequencing. RESULTS: A total of 379 unrelated patients (male: female 219:160) with primary VUR were recruited. Sixty-four (16.9%) children had extrarenal manifestations, and 165 (43.5%) patients showed the coexistence of other CAKUT phenotypes. Eighty-eight patient (23.2%) exhibited impaired renal function at their last visit, and 18 of them (20.5%) developed ESRD at the median age of 7.0 (IQR 0.9-11.4) years. A monogenic cause was identified in 28 patients (7.39%). These genes included PAX2 (n = 4), TNXB (n = 3), GATA3 (n = 3), SLIT2 (n = 3), ROBO2 (n = 2), TBX18 (n = 2), and the other 11 genes (one gene for each patient). There was a significant difference in the rate of gene mutations between patients with or without extrarenal complications (14.1% vs. 6%, P = 0.035). The frequency of genetic abnormality was not statistically significant based on the coexistence of another CAKUT (9.6% vs. 5.6%, P = 0.139, Chi-square test) and the grade of reflux (9.4% vs. 6.7%, P = 0.429). Kaplan-Meier survival curve showed that the presence of genetic mutations did affect renal survival (Log-rank test, P = 0.01). PAX2 mutation carriers (HR 5.1, 95% CI 1.3-20.0; P = 0.02) and TNXB mutation carriers (HR 20.3, 95% CI 2.4-168.7; P = 0.01) were associated with increased risk of progression to ESRD. CONCLUSIONS: PAX2, TNXB, GATA3 and SLIT2 were the main underlying monogenic causes and accounted for up to 46.4% of monogenic VUR. Extrarenal complications and renal function were significantly related to the findings of genetic factors in children with primary VUR. Like other types of CAKUT, several genes may be responsible for isolated VUR.

2.
Bioengineered ; 12(1): 2022-2032, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34060415

RESUMO

Circular RNAs (circRNAs) are a type of non-coding RNAs generated from back splicing to enhance or inhibit the progression of multiple human cancers including osteosarcoma (OS). Although circ_0102049 has been found to be highly expressed in OS cell lines, the role and specific mechanism of circ_0102049 in OS remains unclear. Here, we found that silence of circ_0102049 could significantly exacerbate the tumorigenesis of OS in vivo through sponging microRNA-520g-3p. Polo-like kinase 2 (PLK2) was predicted to be a target of miR-520g-3p, and luciferase reporter assay revealed that overexpression of miR-520g-3p dramatically suppressed the expression of PLK2, whereas miR-520g-3p inhibitor promoted the PLK2 expression. Moreover, the silence of circ_0102049 could markedly promote the proliferation, invasion, migration and cell-cycle promotion while inhibiting the apoptosis of OS cell line MG63 cells in vitro through regulating miR-520g-3p/PLK2 axis. Taken together, the present study indicated that circ_0102049 suppressed the progression of osteosarcoma via modulating miR-520g-3p/PLK2/TAp73 axis, providing a potential therapeutic target for OS.

3.
Leuk Lymphoma ; : 1-9, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34080953

RESUMO

Epstein-Barr virus (EBV) infection is prevalent and associated with distinct diseases including infectious mononucleosis (IM), chronic active EBV infection (CAEBV) and NK/T-cell lymphoma (NKTL). However, the specific roles of EBV in these diseases remain unclear. Here, the whole miRNA expression datasets derived from 7 IM, 6 CAEBV, and 3 NKTL biopsies were obtained. Homo sapiens microRNA-372-5p (Hsa-miR-372-5p) was upregulated in both CAEBV and NKTL patients. Overexpression of hsa-miR-372-5p altered the expression of over 100 proteins. In addition, hsa-miR-372-5p may target NIMA related kinase 7 to regulate NLRP3 inflammasome activation in host cell. Taken together, we reported different miRNA expression profiles in distinct EBV associated diseases, which provided novel insights to understand how host miRNAs contribute to the mechanism of EBV associated diseases. Hsa-miR-372-5p, as well as other differential expressed miRNA, might serve as potential targets in the therapy of various EBV associated diseases.

4.
Laryngoscope ; 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34125440

RESUMO

OBJECTIVES: To compare the results of immediate endoscopic dacryocystorhinostomy (En-DCR) and delayed En-DCR in the treatment of new-onset acute dacryocystitis (AD). STUDY DESIGN: This report describes a prospective randomized controlled interventional case series. METHODS: Between April 2009 and May 2019, 176 adults presenting at a tertiary eye care center with new-onset AD manifesting within the last 48 hours were randomized into two groups. Altogether, 160 patients (48 male, 112 female) were included in this study, with a median age of 52.8 years (range: 18-82). Patients in group A underwent urgent En-DCR, although those in group B underwent a delayed En-DCR after 2 to 5 days of systematic antibiotic treatment. Variables compared between these two groups included the time for resolution of acute external inflammation, free lacrimal passage reconstruction (LPR) success rates, and complication rates. RESULTS: Postoperative data were collected from 86 patients in group A and 74 patients in group B. Patients that underwent immediate En-DCR exhibited a quicker resolution of acute inflammation (P < .05). Patients that underwent delayed surgery experienced compilations of acute inflammation, with 10 ultimately developing skin fistulization and 4 exhibiting orbital cellulitis before surgery. The success rate of LPR at 12 months after surgery was higher in group A (81/86 94.2%) relative to group B (62/74 83.8%; P < .05). CONCLUSIONS: Immediate En-DCR is associated with quicker disease resolution and a higher long-term success rate, although reducing the incidence of complications including skin fistulization and the spread of infection. LEVEL OF EVIDENCE: 3 Laryngoscope, 2021 Laryngoscope, 2021.

5.
Fitoterapia ; : 104959, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34111550

RESUMO

Three new polyprenylated acylphloroglucinol meroterpenoids, hyperiforins A-C (1-3), were isolated from Hypericum forrestii (Chittenden) N. Robson, together with twelve known analogues (4-15). Their structures were established by extensive physical and spectroscopic data analysis. Compounds 1, 2, 5, 7, and 13-15 showed potent inhibitory effects on protein tyrosine phosphatase 1B with IC50 values from 6.63 ±â€¯2.40 to 14.21 ±â€¯3.51 µM.

6.
Int J Mol Sci ; 22(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072880

RESUMO

The segregation of trophectoderm (TE) and inner cell mass in early embryos is driven primarily by the transcription factor CDX2. The signals that trigger CDX2 activation are, however, less clear. In mouse embryos, the Hippo-YAP signaling pathway is important for the activation of CDX2 expression; it is less clear whether this relationship is conserved in other mammals. Lysophosphatidic acid (LPA) has been reported to increase YAP levels by inhibiting its degradation. In this study, we cultured bovine embryos in the presence of LPA and examined changes in gene and protein expression. LPA was found to accelerate the onset of blastocyst formation on days 5 and 6, without changing the TE/inner cell mass ratio. We further observed that the expression of TAZ and TEAD4 was up-regulated, and YAP was overexpressed, in LPA-treated day 6 embryos. However, LPA-induced up-regulation of CDX2 expression was only evident in day 8 embryos. Overall, our data suggest that the Hippo signaling pathway is involved in the initiation of bovine blastocyst formation, but does not affect the cell lineage constitution of blastocysts.

7.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1541-1563, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085442

RESUMO

The regulation of the expression of genes involved in metabolic pathways, termed as metabolic regulation, is vital to construct efficient microbial cell factories. With the continuous breakthroughs in synthetic biology, the mining and artificial design of high-quality regulatory elements have substantially improved our ability to modify and regulate cellular metabolic networks and its activities. The research on metabolic regulation has also evolved from the static regulation of single genes to the intelligent and precise dynamic regulation at the systems level. This review briefly summarizes the advances of metabolic regulation technologies in the past 30 years.


Assuntos
Engenharia Metabólica , Biologia Sintética , Redes e Vias Metabólicas/genética
8.
Artigo em Inglês | MEDLINE | ID: mdl-33979017

RESUMO

Li-CO2 batteries are regarded as next-generation high-energy-density electrochemical devices. However, the greatest challenge arises from the formation of the discharge product, Li2 CO3 , which would accumulate and deactivate heterogenous catalysts to cause huge polarization. Herein, Ru(bpy)3 Cl2 was employed as a solution-phase catalyst for Li-CO2 batteries and proved to be the most effective one screened so far. Spectroscopy and electrochemical analyses elucidate that the RuII center could interact with both CO2 and amorphous Li2 C2 O4 intermediate, thus promoting electroreduction process and delaying carbonate transformation. As a result, the charge potential is reduced to 3.86 V and over 60 discharge/charge cycles are achieved with a fixed capacity of 1000 mAh g-1 at a current density of 300 mA g-1 . Our work provides a new avenue to improve the electrochemical performance of Li-CO2 batteries with efficient mobile catalysts.

9.
Langmuir ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33951392

RESUMO

Surfaces with gradient topography are important in various fields but are difficult to fabricate. Herein, we report a facile and robust way to fabricate a surface with gradient topography of porous structure, in one direction, based on the breath figure (BF) method for the first time. The influencing factors including relative humidity (RH), sample immersion time, and solvent composition, affecting the speed, time, and model of the droplet growth, respectively, were investigated to control gradient BF pores with different ranges of pore sizes. Applying appropriate parameters, gradient BF pores with a diameter difference over 400% were prepared on one sample. The mechanism of gradient duration of solvent evaporation at different regions of a sample for fabricating gradient pores was proposed and experimentally verified with recording optical and thermographic changes of the sample in the BF procedure. This new method provides a novel site for gradient topography fabrication.

10.
Nanoscale ; 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34013941

RESUMO

Water electrolysis is a significant alternative technique to produce clean hydrogen fuel in order to replace environmentally destructive fossil fuel combustion. However, the sluggish oxygen evolution kinetics makes this process vulnerable as it requires relatively high overpotentials. Hence, significantly effective electrocatalysts are necessary to access the water-oxidation process at a low overpotential to make this process industrially viable. Therefore, in order to reduce the energy barrier, we developed bimetallic CoSe2-FeSe2 heteronanoparticles along the carbon nanotube network (CoSe2-FeSe2/CNT) via a facile selenization strategy. Due to the unique assembly of highly conductive nanoparticles along the CNT network, the CoSe2-FeSe2/CNT displays an exceptionally good oxygen evolution (OER) activity; it requires 248 mV overpotential to reach a current density of 10 mA cm-2 (η10) with an ultra-low Tafel slope of 36 mV dec-1 and displays an overpotential of 1.59 V (η10) in the full water-splitting catalysis with the commercial Pt/C cathode. The high OER activity of CoSe2-FeSe2/CNT over the monometallic CoSe2/CNT and FeSe2/CNT electrocatalysts approve the synergistic interactions. Therefore, the superior performance is possibly ascribed to the unique porous nanoarchitecture and the strong coupling interactions between CoSe2 and FeSe2 heteronanoparticles on the conductive network. This study introduces an innovative approach to rationally design and fabricate cost-effective and highly proficient electrocatalysts for boosted OER performance.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34014653

RESUMO

Bismuth telluride alloys have dominated the industrial application of thermoelectric cooling, but the relatively poor mechanical performance of commercial zone-melting material seriously limits the device integration and stability. Here, we exhibit synergistically enhanced thermoelectric and mechanical performances of sintered Bi0.48Sb1.52Te3-AgSbSe2 composites. It is found that the increased hole concentration improves the S2σ to 40 µW cm-1 K-2 at room temperature, and the emerged various defects effectively suppress the κl to 0.57 W m-1 K-1 at 350 K. All effects harvest a highest ZT = 1.2 at 350 K along with an average ZT = 1.0 between 300-500 K in the x = 0.2 sample. Notably, AgSbSe2 addition not only optimizes the thermoelectric properties, but also enhances the mechanical performance with a Vickers hardness of 0.75 GPa. Furthermore, the isotropy of thermoelectric properties is also observably promoted by solid-phase reaction combined with high-energy ball milling and hot pressing. Our study reveals a viable strategy to improve the comprehensive performance of sintered bismuth telluride materials.

12.
Oncogene ; 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34017080

RESUMO

BRAF inhibitors (BRAFi) that target BRAF V600E kinase, a driver mutation found in 50% of melanomas, show a significant antitumor response, but the common emergence of acquired resistance remains a challenge. Abnormal expression of RAF isoforms CRAF and ARAF reactivates pERK1/2, which plays crucial roles in the acquisition of resistance of melanoma cells. However, the mechanisms of dysregulation of RAF isoforms in resistant melanoma cells remain unknown. Here, we identified NONO interacted with and stabilized both CRAF and ARAF in melanoma cells, and that NONO was acetylated at 198K by p300 acetyltransferase, which stabilized NONO via antagonizing its ubiquitination/degradation mediated by RNF8. The upregulation of both p300 and NONO promoted the rebound of pERK1/2 and the subsequent resistance of melanoma cells to BRAFi, and the activation of ERK1/2 in turn induced p300 to form a positive feedback loop in resistant melanoma cells. There was a positive correlation between p300 and NONO in resistant melanoma cells and clinical samples, and p300 inhibitor C646 overcame the resistance of resistant melanoma cells to BRAF inhibitors in vitro and in vivo. Our findings reveal that targeting the positive feedback loop of p300-NONO-CRAF/ARAF-pERK1/2 may be excellent strategies to overcome the resistance of BRAF inhibitors for melanoma patients.

13.
Photodiagnosis Photodyn Ther ; : 102340, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33991660

RESUMO

In recent years, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) has rapidly evolved and has been widely applied in the treatment of skin diseases in China. To further standardize, guide, and promote the clinical applications of ALA-PDT in dermatology, the Chinese Society of Dermatology, Chinese Association of Rehabilitation Dermatology, Photomedicine Therapeutic Equipment Group of Committee on Skin Disease, and Cosmetic Dermatology of China Association of Medical Equipment chose relevant experts engaged in ALA-PDT to revise and update the first edition of "Clinical application of 5-aminolevulinic acid-based photodynamic therapy: an expert consensus statement" and establish this edition of guidelines, to provide a reference for Chinese dermatologists in clinical practice. In the guideline, the expert group reached relatively consistent opinions on ALA-PDT with regard to the mechanisms of action, therapeutic protocol, clinical applications, adverse reactions and countermeasures, precautions, care, and efficacy evaluation.

14.
J Sep Sci ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33942520

RESUMO

Chronic heart failure is a common and fatal disease triggered by loss of normal cardiac function. Yiqi Fumai Lyophilized Injection is widely used in the treatment of cardiovascular diseases, especially chronic heart failure. In this study, a model of chronic heart failure in mice was established with permanent coronary artery ligation followed by Yiqi Fumai Lyophilized Injection intervention for 14 days. Then, the endogenous metabolites of mice plasma and urine samples were screened through nontargeted metabolomics techniques. The results indicated that Yiqi Fumai Lyophilized Injection treatment changed the metabolic pattern of chronic heart failure and regulated valine, leucine, and isoleucine biosynthesis, taurine and hypotaurine metabolism, histidine metabolism and arginine biosynthesis, etc. Finally, the cardioprotective mechanism of Yiqi Fumai Lyophilized Injection was further verified in the mouse model of chronic heart failure and angiotensin II-induced cardiac fibroblasts based on metabolomics. The results showed that Yiqi Fumai Lyophilized Injection could inhibit myocardial fibrosis to improve chronic heart failure. This study firstly elucidated the metabolic network and pathways regulated by Yiqi Fumai Lyophilized Injection, which might facilitate the realization of the clinically accurate application of Yiqi Fumai Lyophilized Injection in the treatment of chronic heart failure.

15.
Int J Clin Pract ; : e14373, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34003587

RESUMO

INTRODUCTION: The resistance exercise effect on the exercise ability in chronic obstructive pulmonary disease (COPD) subjects has drawn considerable attention. However, the relationship between resistance exercise and the exercise ability of COPD subjects is conflicting. This meta-analysis was performed to evaluate this relationship. METHODS: A systematic-literature search up to July 2020 was performed in OVID, Embase, Cochrane Library, PubMed, Google scholar for randomised control trials reported relationships between resistance exercise and the exercise ability of COPD subjects, and 13 studies were detected with 1286 subjects at the baseline. Mean differences (MD) with 95% confidence intervals (CIs) were calculated comparing the resistance exercise and the exercise ability of COPD subjects using the continuous method with a random or fixed-effect model. RESULTS: A significantly higher 6-minutes walk test was observed in subjects performing resistance training (MD, 60.41; 95% CI, 39.97-80.85, P < .001) compared with non-resistance training subjects. However, no significant difference was observed between COPD subjects performing resistance exercise compared with non-resistance training COPD subjects in constant work rate cycle endurance test (MD, 1.59; 95% CI, 0.03-3.15, P = .05), unsupported upper extremity exercise test (MD, 48.77; 95% CI, -1.20 to 98.75, P < .06) and quality of life questionnaires (MD, -0.62; 95% CI, -2.49 to 1.245, P < .51). CONCLUSIONS: The resistance exercise significantly increases the 6-minutes walk test in COPD subjects. However, resistance exercise did not significantly affect the constant work rate cycle endurance test, unsupported upper extremity exercise test and quality of life questionnaires. This relationship forces us to recommend the resistance exercise to improve the 6-minutes walk test as a simple and easy evaluation of functional exercise ability in COPD subjects.

16.
Am J Chin Med ; : 1-14, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34049477

RESUMO

One of the most important aspects of clinical acupuncture practice, like diabetic gastroparesis, is the selection of suitable acupoints. Furthermore, it is critical to examine the therapeutic impact differences between distal and local acupoints, as well as the prescription of their combination. In this study, diabetic gastroparesis rats were treated by needling Zhongwan (CV12) and Zusanli (ST36), and then used Single Photon Emission Computed Tomography-CT (SPECT-CT) technology to assess the effects of promoting gastric motility. In addition, morphological observation, immunohistochemical examination, and biomarker assays, such as determination of growth factor 1, motilin, and ghrelin contents in serum samples, were performed to better understand the impact of certain various acupuncture treatments. All of the therapies improved the symptoms of diabetic gastroparesis rats, according to the findings. Stimulating these acupoints, on the other hand, can have a different therapeutic effect. In addition, needling local and distal acupoints together can have an antagonistic or synergistic impact on specific physiological and biochemical indexes such as gastric motility, ghrelin, gastrin, and growth factor 1, among others. Our findings demonstrated the benefits of acupoints and acupuncture in the management of diabetic gastroparesis, as well as a new insight into acupuncture therapeutics.

17.
J Am Heart Assoc ; 10(11): e019276, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34041919

RESUMO

Background Aortic dissection (AD) is one of the most life-threatening cardiovascular diseases that exhibit high genetic heterogeneity. However, it is unclear whether variants within the COL5A1 gene can cause AD. Therefore, we intend to determine whether COL5A1 is a causative gene of AD. Methods and Results We performed targeted sequencing in 702 patients with unrelated sporadic AD and 163 matched healthy controls using a predesigned panel with 152 vessel matrix-related genes. As a result, we identified that 11 variants in COL5A1 caused AD in 11 out of the 702 patients with AD. Furthermore, Col5a1 knockout (Col5a1+/-) rats were generated through the CRISPR/Cas9 system. Although there was no spontaneous AD, electron microscopy revealed a fracture of elastic fibers and disarray of collagenous fibers in 6-week-old Col5a1+/- rats, but not in WT rats (93.3% versus 0.0%, P<0.001). Three-week-old rats were used to induce the AD phenotype with ß-aminopropionitrile monofumarate for 4 weeks followed by angiotensin II for 72 hours. The ß-aminopropionitrile monofumarate and angiotensin II-treated rat model confirmed that Col5a1+/- rats had considerably higher AD incidence than WT rats. Subsequent mechanism analyses demonstrated that the transforming growth factor-ß-signaling pathway was significantly activated in Col5a1+/- rats. Conclusions Our findings, for the first time, revealed a relationship between variants in COL5A1 and AD via targeted sequencing in 1.57% patients with sporadic aortic dissection. The Col5a1 knockout rats exhibited AD after an intervention, indicating that COL5A1 is a causative gene of AD. Activation of the transforming growth factor-ß-signaling pathway may be implicated in the pathogenesis of this kind of AD.

18.
Front Med ; 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34047934

RESUMO

Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10-6) after 10 000 times permutation test (P = 2.49 × 10-3). Moreover, another independent cohort, including 423 cases and 734 non-STAD subjects (N = 1157), replicated our results (P = 0.021). Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues, and its expression was related to the extracellular matrix (ECM) pathway. Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway. We wanted to expand the knowledge of the genetic basis and pathology of STAD, which may further help in providing better genetic counseling to the patients.

19.
Nat Commun ; 12(1): 2665, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976125

RESUMO

With age, hematopoietic stem cells (HSC) undergo changes in function, including reduced regenerative potential and loss of quiescence, which is accompanied by a significant expansion of the stem cell pool that can lead to haematological disorders. Elevated metabolic activity has been implicated in driving the HSC ageing phenotype. Here we show that nicotinamide riboside (NR), a form of vitamin B3, restores youthful metabolic capacity by modifying mitochondrial function in multiple ways including reduced expression of nuclear encoded metabolic pathway genes, damping of mitochondrial stress and a decrease in mitochondrial mass and network-size. Metabolic restoration is dependent on continuous NR supplementation and accompanied by a shift of the aged transcriptome towards the young HSC state, more youthful bone marrow cellular composition and an improved regenerative capacity in a transplant setting. Consequently, NR administration could support healthy ageing by re-establishing a more youthful hematopoietic system.


Assuntos
Envelhecimento , Células-Tronco Hematopoéticas/efeitos dos fármacos , NAD/metabolismo , Niacinamida/análogos & derivados , Compostos de Piridínio/farmacologia , Fatores Etários , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células Cultivadas , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Niacinamida/farmacologia , Fosforilação Oxidativa/efeitos dos fármacos
20.
Biosci Rep ; 41(6)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-33969376

RESUMO

It has been demonstrated that trimethylamine N-oxide (TMAO) serves as a driver of atherosclerosis, suggesting that reduction of TMAO level might be a potent method to prevent the progression of atherosclerosis. Herein, we explored the role of TMAO in the stability of carotid atherosclerotic plaques and disclosed the underlying mechanisms. The unstable carotid artery plaque models were established in C57/BL6 mice. L-carnitine (LCA) and methimazole (MMI) administration were applied to increase and reduce TMAO levels. Hematoxylin and eosin (H&E) staining, Sirius red, Perl's staining, Masson trichrome staining and immunohistochemical staining with CD68 staining were used for histopathology analysis of the carotid artery plaque. M1 and M2 macrophagocyte markers were assessed by RT-PCR to determine the polarization of RAW264.7 cells. MMI administration for 2 weeks significantly decreased the plaque area, increased the thickness of the fibrous cap and reduced the size of the necrotic lipid cores, whereas 5-week of administration of MMI induced intraplate hemorrhage. LCA treatment further deteriorated the carotid atherosclerotic plaque but with no significant difference. In mechanism, we found that TMAO treatment impaired the M2 polarization and efferocytosis of RAW264.7 cells with no obvious effect on the M1 polarization. In conclusion, the present study demonstrated that TMAO reduction enhanced the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis.

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