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1.
Oxid Med Cell Longev ; 2021: 3206982, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594474

RESUMO

Fibrosis is defined as the pathological progress of excessive extracellular matrix (ECM), such as collagen, fibronectin, and elastin deposition, as the regenerative capacity of cells cannot satisfy the dynamic repair of chronic damage. The well-known features of tissue fibrosis are characterized as the presence of excessive activated and proliferated fibroblasts and the differentiation of fibroblasts into myofibroblasts, and epithelial cells undergo the epithelial-mesenchymal transition (EMT) to expand the number of fibroblasts and myofibroblasts thereby driving fibrogenesis. In terms of mechanism, during the process of fibrosis, the activations of the TGF-ß signaling pathway, oxidative stress, cellular senescence, and inflammatory response play crucial roles in the activation and proliferation of fibroblasts to generate ECM. The deaths due to severe fibrosis account for almost half of the total deaths from various diseases, and few treatment strategies are available for the prevention of fibrosis as yet. Recently, numerous studies demonstrated that three well-defined bioactive gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), generally exhibited anti-inflammatory, antioxidative, antiapoptotic, and antiproliferative properties. Besides these effects, a number of studies have reported that low-dose exogenous and endogenous gasotransmitters can delay and interfere with the occurrence and development of fibrotic diseases, including myocardial fibrosis, idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, diabetic diaphragm fibrosis, and peritoneal fibrosis. Furthermore, in animal and clinical experiments, the inhalation of low-dose exogenous gas and intraperitoneal injection of gaseous donors, such as SNAP, CINOD, CORM, SAC, and NaHS, showed a significant therapeutic effect on the inhibition of fibrosis through modulating the TGF-ß signaling pathway, attenuating oxidative stress and inflammatory response, and delaying the cellular senescence, while promoting the process of autophagy. In this review, we first demonstrate and summarize the therapeutic effects of gasotransmitters on diverse fibrotic diseases and highlight their molecular mechanisms in the process and development of fibrosis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34652859

RESUMO

Topological semimetals with high electrical conductivity and suitable carrier density near Fermi level are enticing candidate materials for electrochemical energy storage meriting from their topologically protected surface states. Here we propose the topological semimetal Co 3 Sn 2 S 2 cathode for aqueous Zn ion batteries (AZIBs) showing an obvious discharge plateau approaching 1.5 V. By further introducing a small amount Sn vacancy, an extra pair of redox peaks (1/1.28 V) appears corresponding to the transition of Sn 4+ /Sn 2+ . Sn vacancy leads to more Zn ion built-in channels and active sites, which promotes charge storage kinetics (Zn 2+ diffusion rate and electron transfer rate) and improves Zn-ion storage capability. The increase of active sites contributes to the enhancement of capacitance behavior. The Co 3 Sn 1.8 S 2 cathode achieves a specific energy of 394 Wh kg -1 (capacity of 343.8 mAh g -1 ) at 0.2 A g -1 and specific power greater than 4900 W kg -1 at 5 A g -1 . The battery also retains a capacity of 193.8 mAh g -1 after 2970 cycles at 1 A g -1 . Benefited from better conductivity at lower temperatures of Co 3 Sn 1.8 S 2 and Zn x Co 3 Sn 1.8 S 2 , the prepared quasi-solid Co 3 Sn 1.8 S 2 //Zn battery delivers superior rate capability even at -30 °C (126 mAh g -1 at 0.6 A/g) and excellent cycling stability over 3000 cycles retaining 85% of the initial capacity at -10 °C and 2 A/g. This work provides new insights for designing novel electrode materials by leveraging topologically protected surface states, incorporating vacancies, and in synergy benefit a lot.

3.
BMC Cancer ; 21(1): 1098, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641822

RESUMO

BACKGROUND: This study aimed to develop a reliable immune signature based on B-cell proportion to predict the prognosis and benefit of immunotherapy in LUAD. METHODS: The proportion of immune cells in the TCGA-LUAD dataset was estimated using MCP-counter. The Least Absolute Shrinkage and Selector Operation was used to identify a prognostic signature and validated in an independent cohort. We used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) data and formalin-fixed paraffin-embedded (FFPE) specimens immunohistochemistry to illustrate the correlation between prognostic signature and leukocyte migration. RESULTS: We found that the relative abundance of B lineage positively correlated with overall survival. Then, we identified a 13-gene risk-score prognostic signature based on B lineage abundance in the testing cohort and validated it in a cohort from the GEO dataset. This model remained strongly predictive of prognoses across clinical subgroups. Further analysis revealed that patients with a low-risk score were characterized by B-cell activation and leukocyte migration, which was also confirmed in FFPE specimens by qRT-PCR and immunohistochemistry. Finally, this immune signature was an independent prognostic factor in the composite nomogram of clinical characteristics. CONCLUSIONS: In conclusion, the 13-gene immune signature based on B-cell proportion may serve as a powerful prognostic tool in LUAD.

5.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 536-544, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494523

RESUMO

Objective To obtain the metabolome profiles in liver and serum of mice during normal aging. Methods The liver and serum samples of ten 2-month-old mice and ten 18-month-old C57BL/6J mice under physiological conditions were collected.Metabolites were identified and quantified by liquid chromatography-tandem mass spectrometry.The overall assessment,differential screening,and functional analysis were performed with the filtered high-quality data. Results In the negative-ion mode and positive-ion mode,242 and 399 metabolites were identified in the liver and 265 and 230 in serum,respectively.The difference of metabolome between young and old mice was moderate.The upregulated metabolites identified in aging liver were related to the metabolism of riboflavin,glucose,and arachidonic acid,while the downregulated ones were associated with the metabolism of pyrimidine,purine,glycerophospholipid,glutathione,and nicotinamide.Altered metabolites in serum during aging were involved in a variety of nucleic acid metabolism-related pathways,such as pyrimidine metabolism,purine metabolism,one carbon pool by folate,and amino sugar and nucleotide sugar metabolism. Conclusions The metabolome profiles of mouse liver and serum both revealed dysregulated nucleic acid metabolism pathways during normal aging.This study provides metabolome data for further research on aging-associated mechanism and may support the discovery of intervention methods for aging.


Assuntos
Metaboloma , Metabolômica , Envelhecimento , Animais , Fígado , Camundongos , Camundongos Endogâmicos C57BL
6.
Proteome Sci ; 19(1): 10, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479544

RESUMO

BACKGROUND: Allergies caused by pollen from Populus deltoides are common, but the allergic components are still unclear. METHODS: The total proteins in pollen of P. deltoides were analyzed by proteomics, and the potential allergens were identified via the WHO/IUIS database and the allergenOnline database retrieval. One target protein was screened by bioinformatics and expressed in Escherichia coli. The biological activity of the expressed product was verified by animal experiments. RESULTS: The total of 3929 proteins in pollen of P. deltoides were identified, and 46 potential allergens belonging to 10 protein families were recognized by database retrieval. B9N9W6 protein of Hsp70 family was screened by bioinformatics analysis and expressed successfully. ELISA showed that B9N9W6 can stimulate the immune system to produce specific IgE and promote the generation of IL-4. Flow cytometry showed that B9N9W6 can significantly stimulate the proliferation of CD4+ T cells and promote the polarization of Th2 cells. The pathological sections of mice lung tissues indicated that alveolar destruction was more severe in the B9N9W6 group than that of extract group, and there were more inflammatory cells infiltration, mucus exudation and bleeding. CONCLUSION: B9N9W6 is an important antigenic substance in the pollen of P. deltoides. Due to the conserved structure of Hsp70 family, more attention should be paid to the possibility of sensitization when Hsp70 from any pathogenic species is administered.

7.
BMC Womens Health ; 21(1): 327, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496817

RESUMO

BACKGROUND: Nowadays, more and more women are engaging in entrepreneurial activities. Meanwhile, female entrepreneurs' health problems have been increasingly reported worldwide. What factors would influence female entrepreneurs' health are the subject of this paper. METHODS: This paper focuses on the effects of entrepreneurial experience and age of firm on female entrepreneurs' health through the analysis of 2 years of tracking data in the Bohai Economic Rim, which is one of the most developed areas for entrepreneurial activities in China. RESULTS: Results from the samples of female entrepreneurs demonstrate that increasing entrepreneurial experience and growing firm age could help female entrepreneurs to activate multiple positive identities. These identities can help female entrepreneurs cope with gender stereotype threat and maintain good health. CONCLUSION: This paper contributes to entrepreneur health research in two aspects. First, this study focused on entrepreneurial history indexed by entrepreneurial experience and firm age, enriching the field of female entrepreneurship. Second, this study further explored the mechanism that women cope with stereotype threat in the context of entrepreneurship. At the same time, this paper addresses ways that policy-makers and social media are responsible to help female entrepreneurs stay healthy.


Assuntos
Adaptação Psicológica , Empreendedorismo , Pré-Escolar , China , Feminino , Nível de Saúde , Humanos
8.
Clin Transl Med ; 11(9): e519, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34586741

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers. The two major lethal causes of ESCC are diagnosis at an advanced stage and lymph node metastasis (LNM). Circular RNAs (circRNAs) play critical regulatory roles in cancer progression, though, largely through unclear mechanisms. However, the character of circRNAs in the malignant progression of ESCC remains unclear. METHODS: The circRNA microarray was used to explore the circRNAs that were differentially expressed between ESCC and paired adjacent normal tissues. The function of circIMMP2L was validated by gain or loss of function assays. Pull-down, RNA immunoprecipitation assays were used to demonstrate the biological mechanism of circIMMP2L. Tissue microarray (TMA), specimen, and paired plasma were investigated to evaluate the clinical significance of circIMMP2L. RESULTS: CircIMMP2L, commonly upregulated in tumor and plasma from advanced-stage ESCC patients and LNM patients, predicts poorer patient survival. CircIMMP2L was also found to be a significant indicator for LNM, even in the T1 stage of ESCC. CircIMMP2L depletion suppressed the malignant progression of ESCC both in vitro and in vivo. Mechanistically, cytoplasmic circIMMP2L interacted with CtBP1 and facilitated the nuclear retention of CtBP1 in a CtBP2-independent manner. Moreover, circIMMP2L promoted the interaction of CtBP1 with HDAC1 in the nucleus, which is essential for epigenetic remodeling and transcriptional suppression of E-cadherin and p21. CONCLUSIONS: These findings demonstrated that circIMMP2L promotes the malignant progression of ESCC mediated by CtBP1 nuclear retention and is a robust biomarker for the diagnosis, prognosis, and LNM in ESCC. Further, the findings extend our knowledge about the mechanism of circRNA regulation of gene transcription through epigenetics.

9.
Environ Pollut ; 291: 118167, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34534827

RESUMO

In recent years, an extensive exposure to antibiotics from various sources has been demonstrated in China by the biomonitoring method, but the temporal trend remains little known. The study aim was to explore the temporal trend of exposure to antibiotics and associated health risk in children. A dynamic child cohort was established in Shanghai, East China between 2017 and 2020. A total of 684 school children aged 7-11 years were included, and 280 in 2017, 279 in 2018, 288 in 2019, and 287 in 2020 participated in annual surveys. Twenty-three typical antibiotics and three metabolites from five categories (four tetracyclines, five qinolones, six macrolides, eight sulfonamides, and three phenicols), bisphenol A (BPA), and monobutyl phthalate (MBP) were determined in urine. Logistic regression analysis with generalized estimating equations was conducted to investigate the associations between various variables and the detection frequency of antibiotics in urine. Seventeen antibiotics and three metabolites were found in 51.9% of all urine samples. Compared to 2017, the detection frequency in urine reduced 31.8% in 2020 for all antibiotics (58.2% vs 39.7%) and reduced 36.8%-55.8% for tetracyclines (11.4% vs 7.0%), qinolones (34.3% vs 21.3%), macrolides (8.6% vs 3.8%), sulfonamides (16.4% vs 8.7%), and phenicols (19.3% vs 12.2%). After accounting for personal characteristics, food consumption, and urinary BPA and MBP, a decreasing temporal trend of detection frequencies was observed from 2017 to 2020 for most antibiotics. Urinary concentration, estimated daily intake, and acceptable daily intake-based health risk of antibiotics showed a temporal trend similar to detection frequency. There was an extensive exposure to antibiotics in children. However, a decreasing temporal trend occurred for the exposure during the period from 2017 to 2020. The trend was likely to be caused by decreased antibiotic use and/or decreased residues in food and/or drinking water.

11.
Int J Mol Sci ; 22(18)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34575918

RESUMO

Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.

12.
J Mater Chem B ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34585188

RESUMO

With the emergence and rapid development of super-resolution fluorescence microscopy, monitoring of mitochondrial morphological changes has aroused great interest for exploring the role of mitochondria in the process of cell metabolism. However, in the absence of water-soluble, photostable and low-toxicity fluorescent dyes, ultra-high-resolution mitochondrial imaging is still challenging. Herein, we designed two fluorescent BODIPY dyes, namely Mito-BDP 630 and Mito-BDP 760, for mitochondrial imaging. The results proved that Mito-BDP 760 underwent aggregation-caused quenching (ACQ) in the aqueous matrix owing to its hydrophobicity and was inaccessible to the cells, which restricted its applications in mitochondrial imaging. In stark contrast, water-soluble Mito-BDP 630 readily penetrated cellular and mitochondrial membranes for mitochondrial imaging with high dye densities under wash-free conditions as driven by membrane potential. As a comparison, Mito Tracker Red presented high photobleaching (the fluorescence intensity dropped by nearly 50%) and high phototoxicity after irradiation by a laser for 30 min. However, Mito-BDP 630 possessed excellent biocompatibility, photostability and chemical stability. Furthermore, clear and bright mitochondria distribution in living HeLa cells after incubation with Mito-BDP 630 could be observed by CLSM. Convincingly, the morphology and cristae of mitochondria could be visualized using an ultra-high-resolution microscope. In short, Mito-BDP 630 provided a powerful and convenient tool for monitoring mitochondrial morphologies in living cells. Given the facile synthesis, photobleaching resistance and low phototoxicity of Mito-BDP 630, it is an alternative to the commercial Mito Tracker Red.

13.
Water Res ; 204: 117628, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34507021

RESUMO

Both biological sulfate reduction process and sulfur reduction process are attractive technologies for metal-laden wastewater treatment. However, the acidity stress of metal-laden wastewater could affect the sulfidogenic performance and the microbial community, weaken the stability, efficiency and cost-effectiveness of the biological sulfidogenic processes (BSP). In this study, long-term lab-scale trials were conducted with a sulfate-reducing bioreactor and a sulfur-reducing bioreactor to evaluate the effects of acidity on sulfidogenic activities and the microbial community of the BSP. In the 300-day trial, the sulfate-reducing bacteria (SRB)-driven BSP was stable in terms of sulfidogenic performance and microbial community with the decline of pH, while the sulfur-reducing bacteria (S0RB)-driven BSP achieved high-rate and low-cost sulfide production under neutral conditions but unstable under acidic conditions. With the decline of pH, the sulfide production rate (SPR) of the SRB-driven BSP stably increased from 30 to 83 mg S/L-h; while it decreased from 56 to 37 mg S/L-h in the S0RB-driven BSP with high fluctuation. The results of estimation were consistent with the thermodynamical calculations, in which the sulfur reduction process showed a better performance at pH 5-7, while the sulfate reduction process might gain more energy when pH<5. The stable sulfidogenic performance and microbial community diversity of the SRB-driven BSP could be attributed to the alkalinity produced in sulfate reduction to buffer the acidic stress. In comparison, the microbial community in the S0RB-driven BSP was significantly re-shaped by acidity stress, and the predominant sulfidogenic bacterium changed from Desulfovibrio at neutral condition, to Desulfurella at pH≤5.4. The stability of the microbial community significantly affected the SPR and the operational cost. Nevertheless, the organic consumption for sulfide production of the S0RB-driven BSP was still less than the SRB-driven BSP even in acidic conditions. Collectively, the S0RB-driven BSP was recommended under neutral or mild acid conditions, while the SRB-driven BSP was more suitable under fluctuating pH conditions, especially at low pH. Overall, this study presented the long-term performance of SRB- and S0RB-driven BSP under varying pH conditions, and provided guidance to determine the suitable BSP and operational cost for different metal-laden wastewater.


Assuntos
Enxofre , Águas Residuárias , Concentração de Íons de Hidrogênio , Metais , Sulfatos
14.
Cancer Cell ; 39(10): 1388-1403.e10, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34506739

RESUMO

Localized radiotherapy (RT) induces an immunogenic antitumor response that is in part counterbalanced by activation of immune evasive and tissue remodeling processes, e.g., via upregulation of programmed cell death-ligand 1 (PD-L1) and transforming growth factor ß (TGF-ß). We report that a bifunctional fusion protein that simultaneously inhibits TGF-ß and PD-L1, bintrafusp alfa (BA), effectively synergizes with radiotherapy, leading to superior survival in multiple therapy-resistant murine tumor models with poor immune infiltration. The BA + RT (BART) combination increases tumor-infiltrating leukocytes, reprograms the tumor microenvironment, and attenuates RT-induced fibrosis, leading to reconstitution of tumor immunity and regression of spontaneous lung metastases. Consistently, the beneficial effects of BART are in part reversed by depletion of cytotoxic CD8+ T cells. Intriguingly, targeting of the TGF-ß trap to PD-L1+ endothelium and the M2/lipofibroblast-like cell compartment by BA attenuated late-stage RT-induced lung fibrosis. Together, the results suggest that the BART combination has the potential to eradicate therapy-resistant tumors while sparing normal tissue, further supporting its clinical translation.

15.
ACS Biomater Sci Eng ; 7(10): 4792-4797, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34491726

RESUMO

Oligomeric cellulose with an average degree of polymerization of 7.68 and a polydispersity of 1.04 has been fractionated using solution processes. Three fractions have been obtained through initial dissolution, subsequent crystallization, and solvent precipitation, respectively. The resulting oligocellulose fraction has an average degree of polymerization of 7.70 and a polydispersity of 1.01, respectively. Cellulose IV2 crystals form in the oligocellulose fraction, and reversibly transform to II and back to IV using simple solvents.

16.
Environ Res ; 204(Pt A): 111990, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34481817

RESUMO

Existing studies on the impact of the COVID-19 pandemic on carbon emissions are mainly based on inter-annual change rate of carbon emissions. This study provided a new way to investigate the impact of the pandemic on carbon emissions by calculating the difference between the pandemic-free carbon emissions and the actual carbon emissions in 2020 based on scenario analysis. In this work, derived from Autoregressive Integrated Moving Average (ARIMA) method and Back Propagation Neural Network (BPNN) method, two combined ARIMA-BPNN and BPNN-ARIMA simulation approaches were developed to simulate the carbon emissions of China, India, U.S. and EU under the pandemic-free scenario. The average relative error of the simulation was about 1%, which could provide reliable simulation results. The scenario simulation of carbon emission reduction in the US and EU were almost the same as the inter-annual change rate of carbon emissions reported by the existing statistics. However, the scenario simulation of carbon emission reduction in China and India is 5% larger than the inter-annual change rate of carbon emissions reported by the existing statistics. In some sense, the impact of the pandemic on carbon emission reduction in developing countries might be underestimated. This work would provide new sight to more comprehensive understanding of the impact of the pandemic on carbon emissions.

17.
J Hazard Mater ; 423(Pt A): 126964, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34523493

RESUMO

Estuaries are sinks for mercury, in which the most toxic mercury form, neurotoxic methylmercury (MeHg), is produced by mercury methylators and accumulates in estuarine sediments. In the same area, the microbial sulfur cycle is triggered by sulfate-reducing bacteria (SRB), which is considered as the main mercury methylator. In this review, we analyzed the sulfur and mercury speciation in sediments from 70 estuaries globally. Abundant mercury and sulfur species were found in the global estuarine sediments. Up to 727 µg THg/g dw and 880 ng MeHg/g dw were found in estuarine sediments, showing the serious risk of mercury to aquatic ecological systems. Significant correlations between sulfur and MeHg concentrations were discovered. Especially, the porewater sulfate concentration positively correlated to MeHg production. The sulfur cycle affects MeHg formation via activating mercury methylator activities and limiting mercury bioavailability, leading to promote or inhibit MeHg formation at different sulfur speciation concentrations. These results suggest that sulfur biogeochemical cycle plays an important role in mercury methylation in estuarine sediments, and the effect of the sulfur cycle on mercury methylation deserves to be further explored in future research.

18.
J Agric Food Chem ; 69(35): 10350-10357, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34448567

RESUMO

As a membrane protein, the activity of angiotensin I-converting enzyme (ACE) can be modulated via regulation of its localization in the cell membrane with food-derived peptides. This study aimed to explore the effect of egg white peptides on the cell membrane localization and activity of ACE in human umbilical vein endothelial cells. ACE activity was found to be related to lipid rafts by using methyl-ß-cyclodextrin (MßCD). QVPLW and LCAY can inhibit ACE activity by preventing ACE recruitment into lipid rafts, with in situ IC50 values of 238.46 ± 11.35 µM and 31.55 ± 2.64 µM in the control groups, as well as 45.43 ± 6.15 µM and 34.63 ± 1.59 µM in the MßCD groups, respectively. QVPLW and LCAY may alter the cell membrane properties, including the fluidity, potential, and permeability, and eventually promote the transposition of ACE.


Assuntos
Clara de Ovo , Peptidil Dipeptidase A , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Microdomínios da Membrana , Peptídeos/farmacologia
19.
J Clin Lab Anal ; 35(9): e23935, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34390017

RESUMO

BACKGROUND: Neutral-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are associated with coronavirus disease 2019 (COVID-19) and many diseases, but there are few data about the reference interval (RI) of NLR, LMR, and PLR. METHODS: The neutrophil count, lymphocyte count, monocyte count, and platelet count of 404,272 Chinese healthy adults (>18 years old) were measured by Sysmex XE-2100 automatic hematology analyzer, and NLR, LMR, and PLR were calculated. According to CLSI C28-A3, the nonparametric 95% percentile interval is defined as the reference interval. RESULTS: The results of Mann-Whitney U test showed that NLR (p < .001) in male was significantly higher than that in female; LMR (p < .001) and PLR (p < .001) in male were significantly lower than that in female. Kruskal-Wallis H test showed that there were significant differences in NLR, LMR, and PLR among different genders and age groups (p < .001). The linear graph showed that the reference upper limit of NLR and PLR increased with age and the reference upper limit of LMR decreases with age in male population. In female population, the reference upper limit of NLR in 50-59 group, LMR in >80 group, and PLR in 70-79 group appeared a trough; the reference upper limit of NLR in >80 group, LMR in 50-59 group, and PLR in 40-49 group appeared peak. CONCLUSION: The establishment of RI for NLR, LMR, and PLR in Chinese healthy adults according to gender and age will promote the standardization of clinical application.


Assuntos
Contagem de Leucócitos/estatística & dados numéricos , Contagem de Linfócitos/estatística & dados numéricos , Monócitos , Neutrófilos , Contagem de Plaquetas/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , SARS-CoV-2 , Fatores Sexuais
20.
Atherosclerosis ; 333: 39-47, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34425526

RESUMO

BACKGROUND AND AIMS: Vascular smooth muscle cells (VSMCs) play a critical role in atherosclerosis. The family with sequence similarity 172, member A (FAM172A) is a novel protein and its role in atherosclerosis has not been explored so far. Therefore, our aim is to investigate whether FAM172A affects atheroprogression through VSMCs and its possible mechanism. METHODS: Fam172a-/- mice were generated using CRISPR/Cas9 technology. Fam172a-/- and Apoe-/- double knockout (Fam172a-/-/Apoe-/-) mice and their littermates (Fam172a+/+/Apoe-/-) were fed with a Western diet for 18 weeks to induce advanced atherosclerotic lesions. The role and mechanism of Fam172a in phenotypic switching, proliferation and migration of VSMCs were investigated through in vivo and in vitro experiments. RESULTS: Compared with Fam172a+/+/Apoe-/- mice, Fam172a-/-/Apoe-/- mice showed increased atherosclerotic lesion size and plaque instability such as increased necrotic core area and decreased fiber deposition. Additionally, knockout of Fam172a promoted expression of CD68 and KLF4 and decreased expression of α-SMA and SM22α in atherosclerotic lesions. Furthermore, overexpression of Fam172a promoted Movas cells proliferation and migration, increased expression of α-SMA and SM22α and decreased expression of KLF4. Meanwhile, knockdown of Fam172a in Movas cells and deletion of Fam172a in VSMCs from Fam172a-/-/Apoe-/- mice showed opposite phenotypes. Similar phenotypes were also observed in human aortic smooth muscle cells. CONCLUSIONS: Our results provide the first direct evidence that Fam172a has a protective role in advanced atherosclerosis by increasing atherosclerotic plaque stability and inhibiting transition of VSMCs from contractile to synthetic phenotype, which may be through KLF4-dependent pathway.

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