Publications by authors named "Juan Ma"

302 Publications

Binding of Benzo[]pyrene Alters the Bioreactivity of Fine Biochar Particles toward Macrophages Leading to Deregulated Macrophagic Defense and Autophagy.

ACS Nano 2021 Jun 14. Epub 2021 Jun 14.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Contaminant-bearing fine biochar particles (FBPs) may exert significantly different toxicity profiles from their contaminant-free counterparts. While the role of FBPs in promoting contaminant uptake has been recognized, it is unclear whether the binding of contaminants can modify the biochemical reactivity and toxicological profiles of FBPs. Here, we show that binding of benzo[]pyrene (B()P, a model polycyclic aromatic hydrocarbon) at environmentally relevant exposure concentrations markedly alters the cytotoxicity of FBPs to macrophages, an important line of innate immune defense against airborne particulate matters (PMs). Specifically, B()P-bearing FBPs elicit more severe disruption of the phospholipid membrane, endocytosis, oxidative stress, autophagy, and compromised innate immune defense, as evidenced by blunted proinflammatory effects, compared with B()P-free FBPs. Notably, the altered cytotoxicity cannot be attributed to the dissolution of B()P from the B()P-bearing FBPs, but appears to be related to B()P adsorption-induced changes of FBPs bioreactivity toward macrophages. Our findings highlight the significance of environmental chemical transformation in altering the bioreactivity and toxicity of PMs and call for further studies on other types of carbonaceous nanoparticles and additional exposure scenarios.
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http://dx.doi.org/10.1021/acsnano.1c00324DOI Listing
June 2021

LncRNA GAS5 modulates the progression of non-small cell lung cancer through repressing miR-221-3p and up-regulating IRF2.

Diagn Pathol 2021 May 22;16(1):46. Epub 2021 May 22.

Department of Respiration, The Sixth People's Hospital of Nantong, Yonghe road No.500, 226011, Nantong, Jiangsu, China.

Background: Long non-coding RNA growth arrest specific 5 (GAS5) is a regulator in non-small cell lung cancer (NSCLC) progression. Nonetheless, the mechanism by which GAS5 exerts its biological function in NSCLC cells remains unclear.

Methods: GAS5, miR-221-3p relative expression levels in NSCLC tissues and cells were examined by qPCR. After gain-of-function and loss-of-function models were established, the viability of H1299 and A549 cells were examined by CCK-8 and EdU assays. Cell migration and invasion were examined by the Transwell experiment. The binding sequence of GAS5 for miR-221-3p was confirmed by the dual-luciferase reporter gene experiment. The regulatory function of GAS5 and miR-221-3p on IRF2 was investigated by Western blot.

Results: GAS5 expression was down-modulated in NSCLC tissues and cell lines. GAS5 overexpression restrained the proliferation, migration and invasion of NSCLC cells, while miR-221-3p, which was targeted and negatively modulated by GAS5, worked oppositely. Restoration of miR-221-3p markedly reversed the effects of GAS5 on NSCLC cells. Additionally, GAS5 increased IRF2 expression in NSCLC cells by repressing miR-221-3p.

Conclusions: GAS5 blocks the progression of NSCLC partly via increasing IRF2 expression level via repressing miR-221-3p.
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http://dx.doi.org/10.1186/s13000-021-01108-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140465PMC
May 2021

Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab in Chinese Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Phase 1 Study.

Antimicrob Agents Chemother 2021 May 10. Epub 2021 May 10.

Phase 1 Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479 or LY-CoV016), in healthy adults. This paper involves a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or a placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose elimination half-life cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.).
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http://dx.doi.org/10.1128/AAC.00350-21DOI Listing
May 2021

Usnic acid suppresses cervical cancer cell proliferation by inhibiting PD-L1 expression and enhancing T-lymphocyte tumor-killing activity.

Phytother Res 2021 May 10. Epub 2021 May 10.

Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China.

The programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is abnormally expressed in cervical cancer cells. Moreover, PD-1/PD-L1 blockade reduces the apoptosis and exhaustion of T cells and inhibits the development of malignant tumors. Usnic acid is a dibenzofuran compound originating from Usnea diffracta Vain and has anti-inflammatory, antifungal, and anticancer activities. However, the molecular mechanism of its antitumor effects has not been fully elucidated. In this work, we first observed that usnic acid decreased the expression of PD-L1 in HeLa cells and enhanced the cytotoxicity of co-cultured T cells toward tumor cells. Usnic acid inhibited PD-L1 protein synthesis by reducing STAT3 and RAS pathways cooperatively. It was subsequently shown that usnic acid induced MiT/TFE nuclear translocation through the suppression of mTOR signaling pathways, and promoted the biogenesis of lysosomes and the translocation of PD-L1 to the lysosomes for proteolysis. Furthermore, usnic acid inhibited cell proliferation, angiogenesis, migration, and invasion, respectively, by downregulating PD-L1, thereby inhibiting tumor growth. Taken together, our results show that usnic acid is an effective inhibitor of PD-L1 and our study provide novel insights into the mechanism of its anticancer targeted therapy.
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http://dx.doi.org/10.1002/ptr.7103DOI Listing
May 2021

First Report of Maize Stalk Rot Caused by Fusarium kyushuense in China.

Plant Dis 2021 Apr 27. Epub 2021 Apr 27.

Chinese Academy of Agricultural Sciences, 12661, Institute of Crop Sciences, Haidian District, Beijing, China;

During 2017 to 2019, a field survey for maize stalk rot was conducted in 21 counties (districts) across the Guangxi province of China. This disease caused yield losses ranging from 20% to 30%. Maize plants with stalk rot were collected during the late milk stage and pieces of diseased pith tissue were cultured as previously described (Shan et al. 2017). Fungal colonies and mycelia with morphological characteristics of Fusarium species were subcultured onto fresh potato dextrose agar (PDA) and carnation leaf agar (CLA) plates. Based on morphological characteristics and molecular detection by amplification of Fusarium genus-specific primers (Duan et al. 2016), 39 Fusarium isolates were identified. Among them, five isolates from Du'an, Pingguo, Debao, and Daxin had abundant, pale orange to yellow aerial mycelium with deep red pigments when grown on PDA (Fig. 1A; 1B). The average growth rate was 8.0 to 12.0 mm per day at 25°C in the dark. The fungi produced two types of spores on CLA. Microconidia were ovoid to clavate, generally 0- to 3-septate, and 4.6 to 9.4 μm in length (n = 30) (Fig. 1D); Macroconidia were slightly curved with an acute apical cell, mostly 3- to 4- septate, and 19.4 to 38.2 μm in length (n = 30) (Fig. 1C). No chlamydospores were observed. These five isolates were initially identified as Fusarium kyushuense based on morphological features. PCR was performed to amplify three phylogenetic genes (TEF1-α, RPB1, and RPB2) (O'Donnell et al. 1998) and species specific primers kyuR1F/kyuR1R (5-TTTTCCTCACCAAGGAGCAGATCATG-3/5-TCCAATGGACTGGGCAGCCAAAACACC-3), kyuR2F/kyuR2R (5-CAGATATACATTTGCCTCGACAC-3/5-TACTTGAGCACGGAGCTTG-3) were used to confirm species identity. The obtained sequences were deposited in GenBank under the accession numbers MT997084, MT997080, MT997081 (TEF1-α); MT550012, MT997085, MT997086 (RPB1); MT550009, MT997089, and MT997090 (RPB2), respectively. Using BLAST, sequences of TEF1-α, RPB1, and RPB2 of the isolates were 99.33% (MH582297.1) to 100% (MG282364.1) similar to those of F. kyushuense strains (Supplementary Table 1). Based on phylogenetic analysis with maximum likelihood methods using tools of the website of CIPRES (http://www.phylo.org), isolates GX27, GX167, and GX204 clustered with F. kyushuense with 100% bootstrap support (Fig. 2). The pathogenicity of the three isolates was tested using young seedlings and adult plants as previously described with modification (Ye et al. 2013; Zhang et al. 2016). The primary roots of three-leaf-old seedlings were inoculated by immersing the roots into a 1 × 106 macroconidia solution, incubating for 6 h at 25°C, and transferring to normal growth conditions (26°C, 16 h light/22°C, 8 h dark). The second or third internode above the soil surface of flowering stage plants grown in a greenhouse was bored with a Bosch electric drill to make a hole (ca. 8 mm in diameter) and inoculated with 0.5 mL of mycelia plug then sealed with petrolatum. The inoculum was created by homogenizing five plates of flourish hyphal mats (approximately 125 mL) with kitchen blender and adjusting to a final volume of 200 mL with sterilized ddH2O. No symptoms were observed in the seedlings or adult plants that were mock-inoculated with PDA plugs. Three days post-inoculation (dpi), roots of the infected seedling turned dark-brown and shrunk and the leaves wilted (Fig. 1E). Typical stalk rot symptoms observed in the inoculated plants were premature wilting of entire plant and hollow and weak stalks, leading to lodging; the longitudinal section of the internodes exhibited obvious dark brown necrosis and reddish discoloration at 14 dpi and 30 dpi, respectively (Fig. 1F). Fusarium kyushuense was re-isolated from the inoculated stalk lesions but not from the control. This is the first record of stalk rot caused by F. kyushuense on maize plants in China. However, F. kyushuense is known to cause maize ear rot in China (Wang et al. 2014) and can produce type A and type B trichothecene mycotoxins in kernels (Aoki and O'Donnell 1998). The occurrence of maize stalk rot and ear rot caused by F. kyushuense should be monitored in China due to the potential risk for crop loss and mycotoxin contamination.
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http://dx.doi.org/10.1094/PDIS-11-20-2342-PDNDOI Listing
April 2021

[Application of Iron and Sulfate-Modified Biochar in Phosphorus Removal from Water].

Huan Jing Ke Xue 2021 May;42(5):2313-2323

School of Environmental and Municipal Engineering, Lanzhou Jiaotong University, Lanzhou 730070, China.

The excessive discharge of phosphate into natural water has caused serious environmental problems. Adsorption is an efficient technology for phosphorus removal from water. In this study, a novel biochar modified by chitosan, ferrous sulfate, and sodium sulfide was synthesized and performed well in phosphorus adsorption. The results of batch experiments showed that the optimum synthesized composite could adsorb 49.32 mg·g of phosphate at 298 K. Meanwhile, the simulation results showed better fitting with the pseudo-second-order model and Langmuir model. The adsorption rate was dominated by three-dimensional diffusion within the inner pores. The adsorption process was defined as physic/chemisorption, while the adsorption mechanism was concluded to be electrostatic adsorption, porous filling, surface chemical precipitation, hydrogen binding, and the ligand effect. This study showed that the composite is effective in phosphorus removal from water, and we anticipate that our research will offer guidelines for adsorbent design and reveal the adsorption mechanism.
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http://dx.doi.org/10.13227/j.hjkx.202008302DOI Listing
May 2021

General Characteristics of Microbubble-Adenovirus Vectors Carrying Genes.

Cell Mol Bioeng 2021 Apr 30;14(2):201-208. Epub 2020 Nov 30.

Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, Urmuqi, 830011 China.

Introduction: Transferring genes safely, targeting cells and achieving efficient transfection are urgent problems in gene therapy that need to be solved. Combining microbubbles (MBs) and viruses to construct double vectors has become a promising approach for gene delivery. Understanding the characteristic performance of MBs that carry genes is key to promoting effective gene transfer. Therefore, in this study, we constructed MB-adenovirus vectors and discussed their general characteristics.

Methods: We constructed MB-adenovirus vectors carrying the chemokine (C-X-C motif) ligand 12 () and bone morphogenetic protein-2 () genes (pAd- and pAd-, respectively) to explore the general characteristics of double vectors carrying genes.

Results: The MB-adenovirus vectors had stable physical properties, and no significant differences in diameter, concentration, or pH were noted compared with naked MBs ( > 0.05). Flow cytometry and RT-PCR were used to detect the gene-loading capacity of MBs. The gene-loading efficiency of MBs increased with increasing virus amounts and was highest (91%) when 10.0 L of virus was added. Beyond 10.0 L of added virus, the gene-loading efficiency of MBs decreased with the continuous addition of virus. The maximum amounts of pAd- and pAd- in 100 L of MBs were approximately 14 and 10 L, respectively.

Conclusions: This study indicates that addition of an inappropriate viral load will result in low MB loading efficiency, and the maximum amount of genes loaded by MBs may differ based on the genes carried by the virus.
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http://dx.doi.org/10.1007/s12195-020-00663-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010034PMC
April 2021

A randomized single-center controlled trial of synchronized intermittent mandatory ventilation with heliox in newborn infants with meconium aspiration syndrome.

Pediatr Pulmonol 2021 Apr 8. Epub 2021 Apr 8.

Department of Neonatology, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

Objective: This study aimed to investigate the beneficial effects of synchronized intermittent mandatory ventilation (SIMV) with heliox in newborn infants with meconium aspiration syndrome (MAS).

Methods: Seventy-one newborn infants with MAS in the neonatal intensive care unit (NICU) of Daping Hospital of Army Medical University were enrolled in the trial. Infants treated with SIMV were randomized and divided into the heliox group (n = 35) and control group (n = 36). The heliox group received heliox for 6 h followed by air-oxygen mixed gas, and the control group received air-oxygen mixed gas. The primary outcome measures were PaO /FiO (P/F) and the extubation time. The secondary outcome measures were the incidence of mechanical ventilation complications, hospital length of stay in the NICU, blood gas analysis, and inflammation markers.

Results: The P/F in the heliox group was significantly better than that in the control group (p < .001). The extubation time and hospital length of stay in the NICU in the heliox group were shorter than those in the control group (p < .001). The inflammation markers at 6 h and myocardial injury markers at 24 h were decreased compared with those at 0 h, and those in the heliox group were more significantly decreased than those in the control group ([interleukin {IL}-6/IL-8/tumor necrosis factor α] p < .001, [C-reaction protein] p = .012; [creatine kinase] p < .001, [CK-MB] p = .041).

Conclusion: Heliox appears to be more effective in reducing the length of ventilation and increasing carbon dioxide eliminations than an air-oxygen mixture in infants with MAS under the support of SIMV.
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http://dx.doi.org/10.1002/ppul.25390DOI Listing
April 2021

Association Mapping and Transcriptome Analysis Reveal the Genetic Architecture of Maize Kernel Size.

Front Plant Sci 2021 18;12:632788. Epub 2021 Mar 18.

Institute of Cereal Crops, Henan Academy of Agricultural Sciences, Zhengzhou, China.

Kernel length, kernel width, and kernel thickness are important traits affecting grain yield and product quality. Here, the genetic architecture of the three kernel size traits was dissected in an association panel of 309 maize inbred lines using four statistical methods. Forty-two significant single nucleotide polymorphisms (SNPs; < 1.72E-05) and 70 genes for the three traits were identified under five environments. One and eight SNPs were co-detected in two environments and by at least two methods, respectively, and they explained 5.87-9.59% of the phenotypic variation. Comparing the transcriptomes of two inbred lines with contrasting seed size, three and eight genes identified in the association panel showed significantly differential expression between the two genotypes at 15 and 39 days after pollination, respectively. Ten and 17 genes identified by a genome-wide association study were significantly differentially expressed between the two development stages in the two genotypes. Combining environment-/method-stable SNPs and differential expression analysis, ribosomal protein L7, jasmonate-regulated gene 21, serine/threonine-protein kinase RUNKEL, AP2-EREBP-transcription factor 16, and Zm00001d035222 (cell wall protein IFF6-like) were important candidate genes for maize kernel size and development.
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http://dx.doi.org/10.3389/fpls.2021.632788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013726PMC
March 2021

[Synthesis of Magnetic Iron Modifying Biochar for Ammonia Nitrogen Removal from Water].

Huan Jing Ke Xue 2021 Apr;42(4):1913-1922

School of Environmental and Municipal Engineering, Lanzhou Jiaotong University, Lanzhou 730070, China.

A significant factor for eutrophication is the excessive discharge of ammonia nitrogen. Unfortunately, traditional methods to remove ammonia nitrogen are ineffective when facing gradually strict rules. Recently, adsorption has gained interest from scholars due to its efficiency and safety in ammonia nitrogen treatment. In this study, a novel biochar, modified with magnetic iron, was synthesized through co-precipitation, which performed well in ammonia nitrogen removal. The maximum adsorption amount at 293 K of the composite that was synthesized at 80℃(MB) was 17.52 mg·g. Meanwhile, the simulation results displayed a good fitting with the pseudo second order model and Langmuir model. Additionally, the adsorption mechanism could be attributed to electrostatic adsorption, porous filling, ion exchange, and hydrogen bonding. Noticeably, MB maintained a good performance after 5 cycles, with desirable adsorption amount of 3.18 mg·g. This study aimed to provide an efficient method to treat ammonia nitrogen as well as a new way to dispose of municipal sludge.
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http://dx.doi.org/10.13227/j.hjkx.202009047DOI Listing
April 2021

Anesthetic management of precise radiotherapy under apnea-like condition.

J Int Med Res 2021 Mar;49(3):300060521990260

Department of Anesthesiology, Wuwei Cancer Hospital of Gansu Province, Wuwei, Gansu, China.

Objective: To study the safety and feasibility of implementation of precise radiotherapy with inducement of an apnea-like condition.

Methods: Two patients with lung tumors underwent precise radiotherapy under an apnea-like condition. The apnea-like condition was induced 11 times between the two patients for tumor localization and treatment. The changes in the blood oxygen saturation, blood pressure, heart rate, and end-tidal carbon dioxide during the apnea-like periods were observed, and the incidence of adverse reactions was recorded.

Results: The average apnea-like time was 6.2 minutes (range, 3-9 minutes), and the average radiotherapy time was 4.6 minutes (range, 1-7 minutes). The lowest blood oxygen saturation level was 97%, with a change of <1%. The heart rate and average arterial blood pressure increased during the apnea-like periods. Contact sores appeared on the patients' posterior pharyngeal wall after the first apnea-like period; no other adverse events occurred.

Conclusion: Precise radiotherapy under an apnea-like condition is safe and feasible for patients with lung tumors.
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http://dx.doi.org/10.1177/0300060521990260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944524PMC
March 2021

Synergistic Impact of Systolic Blood Pressure and Perfusion Status on Mortality in Acute Heart Failure.

Circ Heart Fail 2021 Mar 8;14(3):e007347. Epub 2021 Mar 8.

Emergency Department, Hospital Clínic, Barcelona (V.G., O.M.).

Background: Physical examination remains the cornerstone in the assessment of acute heart failure. There is a lack of adequately powered studies assessing the combined impact of both systolic blood pressure (SBP) and hypoperfusion on short-term mortality.

Methods: Patients with acute heart failure from 41 Spanish emergency departments were recruited consecutively in 3 time periods between 2011 and 2016. Logistic regression models were used to assess the association of 30-day mortality with SBP (<90, 90-109, 110-129, and ≥130 mm Hg) and with manifestations of hypoperfusion (cold skin, cutaneous pallor, delayed capillary refill, livedo reticularis, and mental confusion) at admission.

Results: Among 10 979 patients, 1143 died within the first 30 days (10.2%). There was an inverse association between 30-day mortality and initial SBP (35.4%, 18.9%, 12.4%, and 7.5% for SBP<90, SBP 90-109, SBP 110-129, and SBP≥130 mm Hg, respectively; <0.001) and a positive association with hypoperfusion (8.0%, 14.8%, and 27.6% for those with none, 1, ≥2 signs/symptoms of hypoperfusion, respectively; <0.001). After adjustment for 11 risk factors, the prognostic impact of hypoperfusion on 30-day mortality varied across SBP categories: SBP≥130 mm Hg (odds ratio [OR]=1.03 [95% CI, 0.77-1.36] and OR=1.18 [95% CI, 0.86-1.62] for 1 and ≥2 compared with 0 manifestations of hypoperfusion), SBP 110 to 129 mm Hg (OR=1.23 [95% CI, 0.86-1.77] and OR=2.18 [95% CI, 1.44-3.31], respectively), SBP 90 to 109 mm Hg (OR=1.29 [95% CI, 0.79-2.10] and OR=2.24 [95% CI, 1.36-3.66], respectively), and SBP<90 mm Hg (OR=1.34 [95% CI, 0.45-4.01] and OR=3.22 [95% CI, 1.30-7.97], respectively); -for-interaction =0.043.

Conclusions: Hypoperfusion confers an incremental risk of 30-day all-cause mortality not only in patients with low SBP but also in normotensive patients. On admission, physical examination plays a major role in determining prognosis in patients with acute heart failure.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007347DOI Listing
March 2021

Synthesis and evaluation of the epithelial-to- mesenchymal inhibitory activity of indazole-derived imidazoles as dual ALK5/p38α MAP inhibitors.

Eur J Med Chem 2021 Apr 23;216:113311. Epub 2021 Feb 23.

Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, PR China. Electronic address:

Drugs of targeting both activin receptor-like kinase 5 (ALK5) and p38α have therapeutic advantages, making them attractive treatment options for tumors. Two series of 4-(1H-indazol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazoles 13a-g and 4-(1-methyl-1H-indazol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazoles 20a-g were synthesized and evaluated for ALK5 and p38α mitogen-activated protein kinase inhibitory activity. The most potent compound, 13c (J-1090), inhibited ALK5- and p38α-mediated phosphorylation with half-maximal inhibitor concentrations of 0.004 μM and 0.004 μM, respectively, in the enzymatic assay. In this study, the effectiveness of 13c in transforming growth factor (TGF-β)-exposed U87MG cells was investigated using western blotting, immunofluorescence assays, cell migration assay, invasion assay, and RT-PCR analysis. 13c inhibited the protein expression of Slug and the protein and RNA expression of the mesenchymal-related proteins N-cadherin and vimentin. Furthermore, 13c markedly suppressed TGF-β-induced epithelial-to-mesenchymal transition (EMT), migration, and invasion in U87MG cells. These results suggest that 13c is a novel inhibitor of ALK5 with potential utility in the treatment of human glioma.
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http://dx.doi.org/10.1016/j.ejmech.2021.113311DOI Listing
April 2021

Licochalcone A inhibits proliferation and promotes apoptosis of colon cancer cell by targeting programmed cell death-ligand 1 via the NF-κB and Ras/Raf/MEK pathways.

J Ethnopharmacol 2021 Jun 4;273:113989. Epub 2021 Mar 4.

Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China. Electronic address:

Ethnopharmacological Relevance: Glycyrrhiza glabra L., a traditional medicinal, has a history of thousands of years. It is widely used in clinic and has been listed in Chinese Pharmacopoeia. Licochalcone A is a phenolic chalcone compound and a characteristic chalcone of Glycyrrhiza glabra L. It has many pharmacological activities, such as anti-cancer, anti-inflammatory, anti-viral and anti-angiogenic activities.

Aim Of The Study: In this study, we explored the anti-tumor activity and potential mechanism of licochalcone A in vitro and in vivo.

Materials And Methods: In vitro, the mechanism of licochalcone A at inhibiting PD-L1 expression was investigated by molecular docking, western blotting, RT-PCR, flow cytometry, immunofluorescence and immunoprecipitation assays. The co-culture model of T cells and tumor cells was used to detect the activity of cytotoxic T lymphocytes. Colony formation, EdU labelling and apoptosis assays were used to detect changes in cellular proliferation and apoptosis. In vivo, anti-tumor activity of licochalcone A was assessed in a xenograft model of HCT116 cells.

Results: In the present study, we found that licochalcone A suppressed the expression of programmed cell death ligand-1 (PD-L1), which plays a key role in regulating the immune response. In addition, licochalcone A inhibited the expressions of p65 and Ras. Immunoprecipitation experiment showed that licochalcone A suppressed the expression of PD-L1 by blocking the interaction between p65 and Ras. In the co-culture model of T cells and tumor cells, licochalcone A pretreatment enhanced the activity of cytotoxic T lymphocytes and restored the ability to kill tumor cells. In addition, we showed that licochalcone A inhibited cell proliferation and promoted cell apoptosis by targeting PD-L1. In vivo xenograft assay confirmed that licochalcone A inhibited the growth of tumor xenografts.

Conclusion: In general, these results reveal the previously unknown properties of licochalcone A and provide new insights into the anticancer mechanism of this compound.
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http://dx.doi.org/10.1016/j.jep.2021.113989DOI Listing
June 2021

Comparison of the Long-Acting GnRH Agonist Follicular Protocol with the GnRH Antagonist Protocol in Women Undergoing In Vitro Fertilization: A Systematic Review and Meta-analysis.

Adv Ther 2021 05 2;38(5):2027-2037. Epub 2021 Mar 2.

Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China.

Introduction: To evaluate the effectiveness and safety of long-acting GnRH agonist follicular and GnRH antagonist protocols among women undergoing in vitro fertilization (IVF) using data published in both English-language and Chinese studies.

Methods: We systematically searched the PubMed, Embase, Cochrane, CNKI, and Wanfang databases up to March 2019 for studies comparing long-acting GnRH agonist follicular and GnRH antagonist protocols in women undergoing IVF. The primary outcome was live birth rate; secondary outcomes were clinical pregnancy rate and implantation rate; safety outcomes were ovarian hyperstimulation syndrome (OHSS) and miscarriage rate in fresh cycle. Statistical analysis was done using R software. The study protocol was registered with PROSPERO (CRD42019139396).

Results: In 11 studies that met the inclusion criteria, 1994 women belonged to the long-acting GnRH agonist follicular protocol group and 1678 to the GnRH antagonist protocol group. Live birth rate (relative risk (RR) 1.61; 95% confidence interval (CI) 1.27, 2.05; P < 0.001), clinical pregnancy rate (RR 1.44; 95% CI 1.32, 1.58; P < 0.001), and implantation rate (RR 1.58; 95% CI 1.44, 1.73; P = 0.001) were higher in the long-acting GnRH agonist follicular protocol compared with the antagonist protocol group. There was no difference in miscarriage rate (RR 0.98; 95% CI 0.58, 1.64; P = 0.98) between the long-acting GnRH agonist follicular and antagonist protocols. However, OHSS rate (RR 1.63; 95% CI 1.15, 2.32; P = 0.0058) was lower in the GnRH antagonist protocol compared to the long-acting GnRH agonist protocol group.

Conclusion: The long-acting GnRH agonist follicular protocol was beneficial in improving live birth rate, clinical pregnancy rate, and implantation rate whereas the incidence of OHSS was significantly lower in women undergoing the GnRH antagonist protocol.
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http://dx.doi.org/10.1007/s12325-020-01612-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107074PMC
May 2021

Combinational Antibacterial Activity of Nisin and 3-Phenyllactic Acid and Their Co-production by Engineered .

Front Bioeng Biotechnol 2021 5;9:612105. Epub 2021 Feb 5.

Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.

Nisin produced by certain strains is commercially used in meat and dairy industries because of its effective antibacterial activity and food safety characteristics. It has been proved that the antibacterial activity could be enhanced when combined with other antimicrobial agents. In this study, we demonstrated that nisin and 3-phenyllactic acid (PLA) in combination displayed excellent combinational antibacterial activity against foodborne pathogens including and . The potential application in food preservation was further verified microbial analysis during the storage of meat and milk, and determination of strawberry rot rate. Scanning electron microscopy observation indicated a distinct mode of PLA with nisin, which may target at the dividing cell, contributing to their combinational antibacterial effect of nisin and PLA. Considering the positive results, a nisin-PLA co-producing strain was constructed based on the food-grade strain F44, a nisin Z producer. By the knockout of two L-lactate dehydrogenase (LDH) and overexpression of D-LDH , the yield of PLA was significantly increased 1.77-fold in comparison with the wild type. Anti-bacterial assays demonstrated that the fermentation product of the recombinant strain performed highly effective antibacterial activity. These results provided a promising prospect for the nisin-PLA co-expressing in food preservation on account of its considerable antibacterial activity and cost-effective performance.
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http://dx.doi.org/10.3389/fbioe.2021.612105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901885PMC
February 2021

The FAST-FURO study: effect of very early administration of intravenous furosemide in the prehospital setting to patients with acute heart failure attending the emergency department.

Eur Heart J Acute Cardiovasc Care 2021 Jan 18. Epub 2021 Jan 18.

The GREAT (Global REsearch in Acute cardiovascular conditions Team) Network, Madrid, Spain.

Aims: The effect of early administration of intravenous (IV) furosemide in the emergency department (ED) on short-term outcomes of acute heart failure (AHF) patients remains controversial, with one recent Japanese study reporting a decrease of in-hospital mortality and one Korean study reporting a lack of clinical benefit. Both studies excluded patients receiving prehospital IV furosemide and only included patients requiring hospitalization. To assess the impact on short-term outcomes of early IV furosemide administration by emergency medical services (EMS) before patient arrival to the ED.

Methods And Results: In a secondary analysis of the Epidemiology of Acute Heart Failure in Emergency Departments (EAHFE) registry of consecutive AHF patients admitted to Spanish EDs, patients treated with IV furosemide at the ED were classified according to whether they received IV furosemide from the EMS (FAST-FURO group) or not (CONTROL group). In-hospital all-cause mortality, 30-day all-cause mortality, and prolonged hospitalization (>10 days) were assessed. We included 12 595 patients (FAST-FURO = 683; CONTROL = 11 912): 968 died during index hospitalization [7.7%; FAST-FURO = 10.3% vs. CONTROL = 7.5%; odds ratio (OR) = 1.403, 95% confidence interval (95% CI) = 1.085-1.813; P = 0.009], 1269 died during the first 30 days (10.2%; FAST-FURO = 13.4% vs. CONTROL = 9.9%; OR = 1.403, 95% CI = 1.146-1.764; P = 0.004), and 2844 had prolonged hospitalization (22.8%; FAST-FURO = 25.8% vs. CONTROL = 22.6%; OR = 1.189, 95% CI = 0.995-1.419; P = 0.056). FAST-FURO group patients had more diabetes mellitus, ischaemic cardiomyopathy, peripheral artery disease, left ventricular systolic dysfunction, and severe decompensations, and had a better New York Heart Association class and had less atrial fibrillation. After adjusting for these significant differences, early IV furosemide resulted in no impact on short-term outcomes: OR = 1.080 (95% CI = 0.817-1.427) for in-hospital mortality, OR = 1.086 (95% CI = 0.845-1.396) for 30-day mortality, and OR = 1.095 (95% CI = 0.915-1.312) for prolonged hospitalization. Several sensitivity analyses, including analysis of 599 pairs of patients matched by propensity score, showed consistent findings.

Conclusion: Early IV furosemide during the prehospital phase was administered to the sickest patients, was not associated with changes in short-term mortality or length of hospitalization after adjustment for several confounders.
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http://dx.doi.org/10.1093/ehjacc/zuaa042DOI Listing
January 2021

Understanding false positives and the detection of SARS-CoV-2 using the Cepheid Xpert Xpress SARS-CoV-2 and BD MAX SARS-CoV-2 assays.

Diagn Microbiol Infect Dis 2021 May 2;100(1):115334. Epub 2021 Feb 2.

Depatment of Medicine, Infectious Disease, Central Texas Veterans Healthcare System, Temple, TX, USA.

Several real-time RT-PCR assays have received Emergency Use Authorization from the United States Food and Drug Administration. The BD MAX™ SARS-CoV-2 assay, run by the BD MAX™ system, is a qualitative test that detects the SARS-CoV-2 specific nucleocapsid phosphoprotein gene regions, N1 and N2. The human RNase P gene is used as the endogenous nucleic acid extraction control. The Cepheid Xpert® Xpress SARS-CoV-2 assay, run by the GeneXpert system, detects the pan-sarbecovirus E gene and the N2 region of the N gene. We evaluated the performance characteristics of the BD and Cepheid assays using matched patient samples. We also analyzed comparative Ct values for both assays using 183 positive samples tested at this facility. In addition, we mitigated reporting false positive results without relying on interpretive software. We found that both systems showed comparable sensitivity. We found an approximately 3.5% false positive rate from the BD MAX™ system results.
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http://dx.doi.org/10.1016/j.diagmicrobio.2021.115334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987987PMC
May 2021

Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice.

Redox Biol 2021 04 16;40:101865. Epub 2021 Jan 16.

Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, China; Laboratory of Neuropharmacology of Pharmacy School, and National Clinical Research Center for Aging and Medicine of Huashan Hospital, Fudan University, Shanghai, 201203, China. Electronic address:

Association of both iron/hepcidin and apolipoprotein E (ApoE) with development of Alzheimer disease (AD) and atherosclerosis led us to hypothesize that ApoE might be required for body iron homeostasis. Here, we demonstrated that ApoE knock-out (KO) induced a progressive accumulation of iron with age in the liver and spleen of mice. Subsequent investigations showed that the increased iron in the liver and spleen was due to phosphorylated extracellular regulated protein kinases (pERK) mediated up-regulation of transferrin receptor 1 (TfR1), and nuclear factor erythroid 2-related factor-2 (Nrf2)-dependent down-regulation of ferroportin 1. Furthermore, replenishment of ApoE could partially reverse the iron-related phenotype in ApoE KO mice. The findings imply that ApoE may be essential for body iron homeostasis and also suggest that clinical late-onset diseases with unexplained iron abnormality may partly be related to deficiency or reduced expression of ApoE.
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http://dx.doi.org/10.1016/j.redox.2021.101865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823209PMC
April 2021

In Search of Zonation Markers to Identify Liver Functional Disorders.

Oxid Med Cell Longev 2020 24;2020:9374896. Epub 2020 Dec 24.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

A substantial amount of research is being conducted on zonation markers to identify hepatic injuries and disorders based on the structural and functional zonation of the liver. In contrast to metabolic zonation, hepatocyte ploidy reflects the capability of liver regenerative turnover. Nonetheless, many knowledge gaps remain in the understanding of the links between liver disorders and altered zonation and ploidy, partially owing to the lack of sufficient zonation markers. Under this setting, we recapitulated the currently known and prospective markers used to identify normal and altered liver zonation in different disorders. Furthermore, we discussed new findings from studies that have used advanced methodologies to identify potential markers with greater accuracy. We also elaborated on the perspectives and future applications of zonation research in the early detection of various liver diseases.
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http://dx.doi.org/10.1155/2020/9374896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775176PMC
December 2020

Differences in the microcirculation disturbance in the right and left ventricles of neonatal rats with hypoxic pulmonary hypertension.

Microvasc Res 2021 05 30;135:104129. Epub 2020 Dec 30.

Department of Echocardiography, Xinjiang Key Laboratory of Medical Animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. Electronic address:

Microcirculation disturbance is a crucial pathological basis of heart damage; however, microcirculation alterations induced by hypoxic pulmonary hypertension (HPH) remain unknown, and the left ventricle (LV) in HPH is conventionally ignored. Herein, we investigated the changes in the cardiac structure, function and microcirculation after HPH and further compared the differences between the right ventricle (RV) and LV. Using a neonatal rat model of HPH, we found RV myocardial hypertrophy, dysfunction and poor myocardial perfusion in HPH rats. Additionally, RV microcirculation disturbance manifested as the abnormal expression of endothelin-1/eNOS and increased expression of intercellular cell adhesion molecule-1 (ICAM-1) or E-selectin 3 days after hypoxia, followed by vascular inflammation, coronary arterial remodeling and microvascular sparseness. Impairment in LV vasodilation was detected in rats after 3 days of hypoxia; however, no obvious microvascular rarefaction or inflammatory reaction was observed in the LV. In conclusion, our results suggest that HPH mainly triggers RV microcirculation disturbances, causing low myocardial perfusion damage and cardiac dysfunction. Despite the differences in the RV and LV, their impaired microvascular function, mediated by endothelial cells, occurs almost simultaneously after HPH, earlier than cardiac functional or structural abnormalities.
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http://dx.doi.org/10.1016/j.mvr.2020.104129DOI Listing
May 2021

Britannin stabilizes T cell activity and inhibits proliferation and angiogenesis by targeting PD-L1 via abrogation of the crosstalk between Myc and HIF-1α in cancer.

Phytomedicine 2021 Jan 30;81:153425. Epub 2020 Nov 30.

Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China. Electronic address:

Background: Programmed cell death-ligand 1 (PD-L1) is overexpressed in tumor cells, which causes tumor cells to escape T cell killing, and promotes tumor cell survival, cell proliferation, migration, invasion, and angiogenesis. Britannin is a natural product with anticancer pharmacological effects.

Purpose: In this work, we studied the anticancer potential of britannin and explored whether britannin mediated its effect by inhibiting the expression of PD-L1 in tumor cells.

Methods: In vitro, the mechanisms underlying the inhibition of PD-L1 expression by britannin were investigated by MTT assay, homology modeling and molecular docking, RT-PCR, western blotting, co-immunoprecipitation, and immunofluorescence. The changes in tumor killing activity, cell proliferation, cell cycle, migration, invasion, and angiogenesis were analyzed by T cell killing assays, EdU labeling, colony formation, flow cytometry, wound healing, matrigel transwell invasion, and tube formation, respectively. In vivo, the antitumor activity of britannin was evaluated in the HCT116 cell xenograft model.

Results: Britannin reduced the expression of PD-L1 in tumor cells by inhibiting the synthesis of the PD-L1 protein but did not affect the degradation of the PD-L1 protein. Britannin also inhibited HIF-1α expression through the mTOR/P70S6K/4EBP1 pathway and Myc activation through the Ras/RAF/MEK/ERK pathway. Mechanistically, britannin inhibited the expression of PD-L1 by blocking the interaction between HIF-1α and Myc. In addition, britannin could enhance the activity of cytotoxic T lymphocytes and inhibit tumor cell proliferation and angiogenesis by inhibiting PD-L1. Finally, in vivo observations were confirmed by demonstrating the antitumor activity of britannin in a murine xenograft model.

Conclusion: Britannin inhibits the expression of PD-L1 by blocking the interaction between HIF-1α and Myc. Moreover, britannin stabilizes T cell activity and inhibits proliferation and angiogenesis by inhibiting PD-L1 in cancer. The current work highlights the anti-tumor effect of britannin, providing insights into the development of cancer therapeutics via PD-L1 inhibition.
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http://dx.doi.org/10.1016/j.phymed.2020.153425DOI Listing
January 2021

Enhanced hepatic cytotoxicity of chemically transformed polystyrene microplastics by simulated gastric fluid.

J Hazard Mater 2021 05 12;410:124536. Epub 2020 Nov 12.

College of Environmental Science and Engineering, Hebei University of Science and Technology, Pollution Prevention Biotechnology Laboratory of Hebei Province, Shijiazhuang 050018, China; Hebei Key Laboratory of Molecular Chemistry for Drug, Shijiazhuang 050018, China. Electronic address:

Microplastics pollution has emerged as one of the top-ranked global environmental issues, receiving worldwide attention in recent years. However, knowledge about the detrimental effects of microplastics on human health is still limited. In real-world settings, the physicochemical characteristics of microplastics were modified by environmental and biological transformation, largely changing their ultimate toxicity. Nonetheless, the toxicity change related to transformation of microplastics has not been considered in most published studies thus far. In the current study, we investigated the cytotoxicity of transformed polystyrene microplastics in hepatocytes. Our results revealed that 500 nm polystyrene microplastics, which were chemically transformed by simulated gastricfluid, exacerbated their adverse effects on SMMC-7721 cells at 20 μg/mL for 24 h treatment, including morphological alteration, membrane damage and increased cell apoptosis via oxidative stress. This exacerbated cytotoxicity could be at least partially explained by the degradation, changed surface charge and altered surface chemistry of these polystyrene microplastics after transformation. In conclusion, our study demonstrates that the hepatic cytotoxicity of polystyrene microplastics is enhanced after transformation.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124536DOI Listing
May 2021

Erianin regulates programmed cell death ligand 1 expression and enhances cytotoxic T lymphocyte activity.

J Ethnopharmacol 2021 Jun 19;273:113598. Epub 2020 Nov 19.

Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China. Electronic address:

Ethnopharmacological Relevance: Dendrobium chrysotoxum Lindl is a cultivation of Dendrobium which belongs to the family of Orchidaceae. D. chrysotoxum Lindl is a traditional Chinese medicine with a wide range of clinical applications including tonic, astringent, analgesic and anti-inflammatory properties as early as the 28th century B.C. Erianin is a representative index component for the quality control of the D. chrysotoxum Lindl, which is included in the Pharmacopoeia of the People's Republic of China (2020 version).

Aim Of The Study: To clarify the anti-tumour mechanisms of erianin in vitro and in vivo.

Materials And Methods: We detected the anti-tumour activity of erianin using in vitro HeLa cell models and in vivo cervical cancer xenograft models. We performed MTT, western blot, RT-PCR, homology modeling, flow cytometry, and immunoprecipitation assays to study the proteins, genes, and pathways related to erianin's anti-tumour activity. LysoTracker Red staining was performed to detect lysosome function. Transwell, wound healing, tube formation, colony formation and EdU labelling assays were performed to determine cell proliferation, migration and invasion abilities, respectively. Cytotoxic T lymphocytes ability was confirmed using HeLa/T-cell co-culture model.

Results: Experimental data demonstrated that erianin inhibited PD-L1 expression and induced the lysosomal degradation of PD-L1. Erianin suppressed HIF-1α synthesis through mTOR/p70S6K/4EBP1 pathway, and inhibited RAS/Raf/MEK/MAPK-ERK pathway. Immunoprecipitation experiments demonstrated that erianin reduced the interaction between RAS and HIF-1α. Experiments using a co-cultivation system of T cells and HeLa cells confirmed that erianin restored cytotoxic T lymphocytes ability to kill tumour cells. Erianin inhibited PD-L1-mediated angiogenesis, proliferation, invasion and migration. The anti-proliferative effects of erianin were supported using in vivo xenotransplantation experiments.

Conclusions: Collectively, these results revealed previously unknown properties of erianin and provided a new basis for improving the efficacy of immunotherapy against cervical cancer and other malignant tumours through PD-L1.
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http://dx.doi.org/10.1016/j.jep.2020.113598DOI Listing
June 2021

Prediction of liver iron overload in the Basque country (Spain) in patients referred for hyperferritinemia.

Dig Liver Dis 2021 Jan 13;53(1):137-138. Epub 2020 Nov 13.

Clinical Epidemiology Unit, CASPe, CIBER-ESP, Donostia University Hospital, Donostia, Spain.

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http://dx.doi.org/10.1016/j.dld.2020.10.010DOI Listing
January 2021

Perioperative nurses' experiences in relation to surgical patient safety: A qualitative study.

Nurs Inq 2021 04 5;28(2):e12390. Epub 2020 Nov 5.

Nursing Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Sant Cugat, Spain.

Surgical patient safety remains a concern worldwide as, despite World Health Organization recommendations and implementation of its Surgical Safety Checklist, adverse events continue to occur. The aim of this qualitative study was to explore the views and experiences of perioperative nurses regarding the factors that impact surgical patient safety. Data were collected through five focus groups involving a total of 50 perioperative nurses recruited from four public hospitals in Spain. Content analysis of the focus groups yielded four main themes: personal qualities of the perioperative nurse, the surgical environment, safety culture, and perioperative nursing care plans. One of the main findings concerned barriers to the exercise of leadership by nurses, especially regarding completion of the Surgical Safety Checklist. Some of the key factors that impacted the ability of perioperative nurses to fulfil their duties and ensure patient safety were the stress associated with working in the operating room, time pressures, and ineffective communication in the multidisciplinary team. Targeting these aspects through training initiatives could contribute to the professional development of perioperative nurses and reduce the incidence of adverse events by enhancing the surgical safety culture.
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http://dx.doi.org/10.1111/nin.12390DOI Listing
April 2021

Analysis of standards of quality for outcomes in acute heart failure patients directly discharged home from emergency departments and their relationship with the emergency department direct discharge rate.

J Cardiol 2021 Mar 12;77(3):245-253. Epub 2020 Oct 12.

Emergency Department, Hospital Clínico San Carlos, Madrid, Instituto de Investigación Sanitaria San Carlos (IdISSC), Universidad Complutense de Madrid, Spain.

Objective: Experts recommended that direct discharge without hospitalization (DDWH) for emergency departments (EDs) able to observe acute heart failure (AHF) patients should be >40%, and these discharged patients should fulfil the following outcome standards: 30-day all-cause mortality <2% (outcome A); 7-day ED revisit due to AHF < 10% (outcome B); and 30-day ED revisit/hospitalization due to AHF < 20% (outcome C). We investigated these outcomes in a nationwide cohort and their relationship with the ED DDWH percentage.

Methods: We analyzed the EAHFE registry (includes about 15% of Spanish EDs), calculated DDWH percentage of each ED, and A/B/C outcomes of DDWH patients, overall and in each individual ED. Relationship between ED DDWH and outcomes was assessed by linear and quadratic regression models, non-weighted and weighted by DDWH patients provided by each ED.

Results: Among 17,420 patients, 4488 had DDWH (25.8%, median ED stay = 0 days, IQR = 0-1). Only 12.9% EDs achieved DDWH > 40%. Considering DDWH patients altogether, outcomes A/C were above the recommended standards (4.3%/29.4%), while outcome B was nearly met (B = 10.1%). When analyzing individual EDs, 58.1% of them achieved the outcome B standard, while outcomes A/C standards were barely achieved (19.3%/9.7%). We observed clinically relevant linear/quadratic relationships between higher DDWH and worse outcomes B (weighted R = 0.184/0.322) and C (weighted R = 0.430/0.624), but not with outcome A (weighted R = 0.002/0.022).

Conclusions: The EDs of this nationwide cohort do not fulfil the standards for AHF patients with DDWH. High DDWH rates negatively impact ED revisit or hospitalization but not mortality. This may represent an opportunity for improvement in better selecting patients for early ED discharge and in ensuring early follow-up after ED discharge.
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http://dx.doi.org/10.1016/j.jjcc.2020.09.002DOI Listing
March 2021

Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB pathways.

Br J Pharmacol 2020 11 19;177(22):5224-5245. Epub 2020 Oct 19.

Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin, China.

Background And Purpose: Arctigenin, a major bioactive component of Fructus arctii, has been reported to have antidepressant-like effects. However, the mechanisms underlying these effects are still unclear. Neuroinflammation can be caused by excessive production of proinflammatory cytokines in microglia via high-mobility group box 1 (HMGB1)/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways, leading to depression. In this study, we have investigated the antidepressant mechanism of arctigenin by conducting in vitro and in vivo studies.

Experimental Approach: The effects of chronic unpredictable mild stress (CUMS) on wild-type (WT) and TLR4 mice were examined. Antidepressant-like effects of arctigenin were tested using the CUMS-induced model of depression in WT mice. The effects of arctigenin were assessed on the HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways in the prefrontal cortex (PFC) of mouse brain and HMGB1- or TNF-α-stimulated primary cultured microglia. The interaction between HMGB1 and TLR4 or TNF-α and TNFR1 with or without arctigenin was examined by localized surface plasmon resonance (LSPR) and co-immunoprecipitation assays.

Key Results: The immobility times in the tail suspension test (TST) and forced swimming test (FST) were reduced in TLR4 mice, compared with WT mice. Arctigenin exhibited antidepressant-like effects. Arctigenin also inhibited microglia activation and inflammatory responses in the PFC of mouse brain. Arctigenin inhibited HMGB1 and TLR4 or TNF-α and TNFR1 interactions, and suppressed both HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways.

Conclusions And Implications: Arctigenin has antidepressant-like effects by attenuating excessive microglial activation and neuroinflammation through the HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways. This suggests that arctigenin has potential as a new drug candidate suitable for clinical trials to treat depression.
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http://dx.doi.org/10.1111/bph.15261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589024PMC
November 2020

Antiviral nanoagents: More attention and effort needed?

Nano Today 2020 Dec 18;35:100976. Epub 2020 Sep 18.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

The recent COVID-19 outbreak has increasingly engaged researchers in the search for effective antiviral drugs as well as therapeutic treatment options. The shortcomings of existing antiviral agents such as narrow spectrum and low bioavailability, can be overcome through the use of engineered nanomaterials, which, therefore, are considered as a significant next-generation therapeutic option. Thus, the development of novel antiviral nanoagents will certainly help address several future challenges and knowledge gaps.
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http://dx.doi.org/10.1016/j.nantod.2020.100976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498411PMC
December 2020