Publications by authors named "Ming Yuan"

348 Publications

Comprehensive Investigation on Ginsenosides in Different Parts of a Garden-Cultivated Ginseng Root and Rhizome.

Molecules 2021 Mar 18;26(6). Epub 2021 Mar 18.

Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing 100850, China.

Background: Ginseng is widely used as herb or food. Different parts of ginseng have diverse usages. However, the comprehensive analysis on the ginsenosides in different parts of ginseng root is scarce.

Methods: An ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) combined with UNIFI informatics platform and ultra-high-performance liquid chromatography-charged aerosol detection (UHPLC-CAD) were employed to evaluate the different parts of cultivated ginseng root.

Results: 105 ginsenosides including 16 new compounds were identified or tentatively characterized. 22 potential chemical markers were identified, 20, 17, and 19 for main root (MR) and fibrous root (FR), main root (MR) and branch root (BR), and main root (MR) and rhizome (RH), respectively. The relative contents of Re, Rb, 20(R)-Rh, Rd, and Rf were highest in FR. The relative content of Rg was highest in RH. The total relative content of pharmacopoeia indicators Rg, Re, and Rb was highest in FR.

Conclusion: The differences among these parts were the compositions and relative contents of ginsenosides. Under our research conditions, the peak area ratio of Rg and Re could distinguish the MR and FR samples. Fibrous roots showed rich ingredients and high ginsenosides contents which should be further utilized.
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http://dx.doi.org/10.3390/molecules26061696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003075PMC
March 2021

Chemical Composition, Antioxidant, Antimicrobial, and Phytotoxic Potential of Leaves Essential Oils.

Molecules 2021 Mar 7;26(5). Epub 2021 Mar 7.

College of Life Science, Sichuan Agricultural University, Ya'an 625014, China.

was a unique hybridization in China. However, the chemical and pharmacological properties were rarely reported. Therefore, in this work, we used a steam distillation method to obtain essential oils from leaves of , and further evaluated the antioxidant, antimicrobial, and phytotoxic potential of the essential oil. Gas chromatography mass spectrometry (GC-MS) was applied to investigate the chemical composition of essential oil (EEO) and the results showed that the main components of EEO were monoterpenes followed by sesquiterpenes. Among them, α-pinene accounted about 17.02%. EEO could also well scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals showing a good free radical clearance ability. In addition, EEO efficiently inhibited the growth of six kinds of bacteria as well as seven kinds of plant pathogens, especially and . Moreover, the seedling germination of , , , and was significantly suppressed by EEO, thus, indicating essential oils from possessed an excellent phytotoxic activity. This study may give a better understanding on EEO and provide a pharmacological activities analysis contributing to the further research of EEO as a functional drug in agronomic and cosmetic industries.
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http://dx.doi.org/10.3390/molecules26051450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962113PMC
March 2021

Phosphorous doped g-CN supported cobalt phthalocyanine: An efficient photocatalyst for reduction of CO under visible-light irradiation.

J Colloid Interface Sci 2021 Feb 7;594:658-668. Epub 2021 Feb 7.

Institute of Chemical and Industrial Bioengineering, Jilin Engineering Normal University, Changchun 130052, China.

The photoreduction of the green-house gas CO into carbon monoxide (CO) is a growing process due to the use of CO for the production of methanol in the Fischer-Tropsch process and the synthesis of many of the bulk chemicals. Here, we have synthesized phosphorous doped graphitic carbon nitride (P-g-CN) sensitized by the cobalt phthalocyanine complex for the molecular reduction of CO into CO under visible-light irradiation-the doping of phosphorous improved the stability as well as the harvesting of the visible region. The CoPc@P-g-CN hybrid photocatalyst exhibited the highest efficiency for the photoreduction of CO with a high yield of 295 μmol-g for CO under the experimental conditions. Also, hydrogen with low concentration was identified as a by-product under the experimental conditions. The photocatalyst had stability for six consecutive runs with negligible loss of the activity and no leaching of the cobalt content at the end of the sixth run of the photoreduction experiment. The stability of the photocatalysts is an advantage, which made it a suitable candidate for the current reaction system.
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http://dx.doi.org/10.1016/j.jcis.2021.02.005DOI Listing
February 2021

Clinical features, laboratory findings and persistence of virus in 10 children with coronavirus disease 2019 (COVID-19).

Biomed J 2020 Oct 24. Epub 2020 Oct 24.

Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. Electronic address:

Background: A pandemic caused by SARS-CoV-2 infection (COVID-19) has rapidly spread across the globe. Although many articles have established the clinical characteristics of adult COVID-19 patients so far, limited data are available for children. The aim of this study was to reveal the clinical features, laboratory findings and nucleic acid test results of ten pediatric cases.

Methods: In this retrospective single-center cohort study, pediatric cases with COVID-19 infection were consecutively enrolled in one hospital in Huangshi, China from January 1 to March 11, 2020.

Results: A total of 10 children with COVID-19 were recruited. Of them, four were the asymptomatic type, one was the mild type, and five were the moderate type (including two subclinical ones). All patients were from family clusters. Only fever, nasal discharge and nasal congestion were observed. Lymphopenia and leukopenia were uncommon in our sample but elevated levels of lactate dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (α-HBDH) were observed frequently. Of these laboratory test variables, no statistical difference was identified between asymptomatic and symptomatic patients. Abnormalities in radiological data were detected in five patients, and representative findings of chest CT images were patchy shadows and ground-glass opacities. There were two cases whose oropharyngeal nucleic acid tests reversed to positive after one negative result, and two patients whose oropharyngeal swabs tested negative but rectal swabs showed positive.

Conclusions: Clinical symptoms were mild in children with COVID-19. Increased levels of LDH and α-HBDH were potential clinical biomarkers for pediatric cases. More attention should be paid to the SARS-CoV-2 viral assessment of rectal swabs before patients are discharged.
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http://dx.doi.org/10.1016/j.bj.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585360PMC
October 2020

Comparative analysis of chemical components in different parts of Epimedium Herb.

J Pharm Biomed Anal 2021 May 17;198:113984. Epub 2021 Feb 17.

Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address:

Epimedium herb is a well-known traditional Chinese medicine (TCM) that is used for treating kidney-yang deficiency, impotence and rheumatism, and flavonoids are the main active ingredients. The leaves and rhizomes of Epimedium herb are two separate kinds of medicinal materials with different functional indications and clinical applications. This study aimed to comprehensively analyze the chemical components of different parts of the herb from three Epimedium species (Epimedium sagittatum, E. pubescens and E. myrianthum) by using ultra high-performance liquid chromatography coupled with photo-diode array and quadrupole time-of-flight mass spectrometry (UHPLC-PDA-Q-TOF/MS) and multivariate statistical analysis to clarify the differences. Firstly, the workflow of UHPLC-Q-TOF/MS combined with UNIFI informatics was developed for characterizing the chemical compounds in different parts of Epimedium herb. Based on the exact mass information, the fragmentation characteristics and the retention times of compounds, all chromatographic peaks (74 chemical components) were identified. Secondly, 21 potential chemical markers for differentiating different parts of Epimedium herb were selected through PCA and PLS-DA analysis. The characteristic components in the leaves included flavonoids with Anhydroicaritin (type A, C-4' linked methoxy) as the backbone, and the characteristic components in the stems and rhizomes were Magnoline and flavonoids with Demethylanhydroicaritin (type B, C-4' linked hydroxyl) as the backbone. Thirdly, the UHPLC-PDA combined with heatmap visualization was employed to clarify the distribution of chemical components with high content in different parts of Epimedium herb. The results showed clear differences in the contents of chemical components in leaves, stems and rhizomes. The levels of flavonoids with Anhydroicaritin backbone were high in the leaves, and levels of flavonoids with Demethylanhydroicaritin backbone were high in the rhizomes. The levels of Magnoline in stems and rhizomes were higher than that in leaves. The contents of most of the compounds in stems remained low. The leaves and the other two parts (stems and rhizomes) can be distinguished by qualitative and semi-quantitative analysis of Magnoline and Epimedoside A (type B backbone). These results indicated that the different plant parts of Epimedium herb can be quickly and accurately distinguished by this method, establishing a foundation for the application of Epimedium herb.
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http://dx.doi.org/10.1016/j.jpba.2021.113984DOI Listing
May 2021

Correction to: PRSS8 suppresses colorectal carcinogenesis and metastasis.

Oncogene 2021 Mar;40(10):1922-1924

Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining, 272067, China.

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http://dx.doi.org/10.1038/s41388-021-01646-3DOI Listing
March 2021

E3 ligase Nedd4l promotes antiviral innate immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3.

Nat Commun 2021 02 19;12(1):1194. Epub 2021 Feb 19.

Clinical Cancer Institute, Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China.

Ubiquitination is one of the most prevalent protein posttranslational modifications. Here, we show that E3 ligase Nedd4l positively regulates antiviral immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3. Deficiency of Nedd4l significantly impairs type I interferon and proinflammatory cytokine production induced by virus infection both in vitro and in vivo. Nedd4l deficiency inhibits virus-induced ubiquitination of TRAF3, the binding between TRAF3 and TBK1, and subsequent phosphorylation of TBK1 and IRF3. Nedd4l directly interacts with TRAF3 and catalyzes K29-linked ubiquitination of Cys56 and Cys124, two cysteines that constitute zinc fingers, resulting in enhanced association between TRAF3 and E3 ligases, cIAP1/2 and HECTD3, and also increased K48/K63-linked ubiquitination of TRAF3. Mutation of Cys56 and Cys124 diminishes Nedd4l-catalyzed K29-linked ubiquitination, but enhances association between TRAF3 and the E3 ligases, supporting Nedd4l promotes type I interferon production in response to virus by catalyzing ubiquitination of the cysteines in TRAF3.
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http://dx.doi.org/10.1038/s41467-021-21456-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895832PMC
February 2021

Structural characterization and statistical properties of jammed soft ellipsoid packing.

Soft Matter 2021 Mar;17(10):2963-2972

Shanghai Key Laboratory of Magnetic Resonance, Institute of Materials, School of Physics and Electronic Science, East China Normal University, Shanghai 200241, P. R. China.

The jamming transition and jammed packing structures of hydrogel soft ellipsoids are studied using magnetic resonance imaging techniques. As the packing fraction increases, the fluctuation of local free volume decreases and the fluctuation of particle deformation increases. Effective thermodynamic quantities are obtained by characterizing these fluctuations using k-gamma distributions based on an underlying statistical model for granular materials. Surprisingly, the two granular temperatures measuring the relative fluctuations of both free volume and particle deformation remain basically unchanged as the packing fraction increases. The total configurational entropy is also approximately constant for packing with different packing fractions. The significantly different behaviors of these effective thermodynamic quantities compared with hard sphere systems are further attributed to a statistically affine structural transformation of the packing structures along with particle deformations when the packing fraction changes.
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http://dx.doi.org/10.1039/d0sm01699cDOI Listing
March 2021

A systemically deliverable Vaccinia virus with increased capacity for intertumoral and intratumoral spread effectively treats pancreatic cancer.

J Immunother Cancer 2021 Jan;9(1)

Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK

Background: Pancreatic cancer remains one of the most lethal cancers and is refractory to immunotherapeutic interventions. Oncolytic viruses are a promising new treatment option, but current platforms demonstrate limited efficacy, especially for inaccessible and metastatic cancers that require systemically deliverable therapies. We recently described an oncolytic vaccinia virus (VV), VVLΔTKΔN1L, which has potent antitumor activity, and a regime to enhance intravenous delivery of VV by pharmacological inhibition of pharmacological inhibition of PI3 Kinase δ (PI3Kδ) to prevent virus uptake by macrophages. While these platforms improve the clinical prospects of VV, antitumor efficacy must be improved.

Methods: VVLΔTKΔN1L was modified to improve viral spread within and between tumors via viral B5R protein modification, which enhanced production of the extracellular enveloped virus form of VV. Antitumor immunity evoked by viral treatment was improved by arming the virus with interleukin-21, creating VVL-21. Efficacy, functional activity and synergy with α-programmed cell death protein 1 (α-PD1) were assessed after systemic delivery to murine and Syrian hamster models of pancreatic cancer.

Results: VVL-21 could reach tumors after systemic delivery and demonstrated antitumor efficacy in subcutaneous, orthotopic and disseminated models of pancreatic cancer. The incorporation of modified B5R improved intratumoural accumulation of VV. VVL-21 treatment increased the numbers of effector CD8+ T cells within the tumor, increased circulating natural killer cells and was able to polarize macrophages to an M1 phenotype in vivo and in vitro. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1.

Conclusions: Intravenously administered VVL-21 successfully remodeled the suppressive tumor-microenvironment to promote antitumor immune responses and improve long-term survival in animal models of pancreatic cancer. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1. Combination of PI3Kδ inhibition, VVL-21 and α-PD1 creates an effective platform for treatment of pancreatic cancer.
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http://dx.doi.org/10.1136/jitc-2020-001624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839893PMC
January 2021

Community engagement in public health: a bibliometric mapping of global research.

Arch Public Health 2021 Jan 12;79(1). Epub 2021 Jan 12.

College of Computer and Information Engineering, Hohai University, Nanjing, China.

Background: Community engagement (CE) has been regarded as a critical element of successful health programs to achieve "the health for all" goals. Numerous studies have shown that it plays a significant role in reducing inequalities, improving social justice, enhancing benefits, and sharing responsibility towards public health. Despite this, the extant literature of community engagement in public health (CEPH) has topic-focused boundaries and is scattered across disciplinary. Large-scale studies are needed to systematically identify current status, hotspots, knowledge structure, dynamic trends, and future developments in this field.

Methods: The bibliometric techniques were applied in the analysis of publications on CEPH in Web of Science Core Collection from Thomson Reuters. One thousand one hundred two papers out of 70.8 million publications over the period of 1980 to 2020 and their 15,116 references were retrieved as the sample set. First, basic characteristics of publications, including distributions of geography, journals and categories, productive authors and frequently cited articles, etc. were obtained. Then, four bibliometric methods, i.e. social network analysis, co-citation analysis, co-occurrence clustering, and burst detection, were further conducted to sketch the contours of the structure and evolution of CEPH.

Results: Between Jan 1, 1980, and Apr 25, 2020, CEPH has attracted a sharp increase in interest all over the world. Total 117 countries or regions have participated in the field of CEPH and the contributions are geographically and institutionally distinct. The United States is the key region performing such research, which accounts for more than half of the total number of publications. Developing countries, such as South Africa, India, Brazil and China also contributed a lot. The advancements of CEPH are marked by historically momentous public health events and evolved from macroscopic strategies to mesoscopic and microscopic actions. Based on keyword clustering and co-citation clustering, we propose a 4O (i.e. orientation, object, operation, and outcome) framework of CEPH to facilitate a better understanding of the current global achievements and an elaborate structuring of developments in the future.

Conclusion: This study draws an outline of the global review on the contemporary and cross-disciplinary research of CEPH which might present an opportunity to take stock and understand the march of knowledge as well as the logical venation underlying research activities which are fundamental to inform policy making.
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http://dx.doi.org/10.1186/s13690-021-00525-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801880PMC
January 2021

Berberine-Loaded Thiolated Pluronic F127 Polymeric Micelles for Improving Skin Permeation and Retention.

Int J Nanomedicine 2020 8;15:9987-10005. Epub 2020 Dec 8.

College of Food and Drug, Luoyang Normal University, Luoyang 471934, People's Republic of China.

Background: Challenges associated with local antibacterial and anti-inflammatory drugs include low penetration and retention of drugs at the expected action site. Additionally, improving these challenges allows for the prevention of side effects that are caused by drug absorption into the systemic circulation and helps to safely treat local skin diseases.

Methods: In the current study, we successfully prepared a thiolated pluronic F127 polymer micelles (BTFM), which binds to keratin through a disulphide bond, to produce skin retention. In addition, the small particle size of polymer micelles promotes the penetration of carriers into the skin. The current study was divided into two experiments: an in vitro experiment; an in vivo experiment that involved the penetration of the micelle-loaded drugs into the skin of rats, the skin irritation test and the anti-inflammatory activity of the drug-loaded micelles on dimethyl benzene-induced ear edema in mice.

Results: Results from our in vitro transdermal experiment revealed that the amount of drug absorbed through the skin was decreased after the drug was loaded in the BTFM. Further, results from the vivo study, which used fluorescence microscopy to identify the location of the BTFM after penetration, revealed that there was strong fluorescence in the epidermis layer, but there was no strong fluorescence in the deep skin layer. In addition, the BTFM had a very good safety profile with no potentially hazardous skin irritation and transdermal administration of BTFM could significantly suppress ear edema induced by dimethyl benzene. Therefore, these findings indicated that BTFM reduced the amount of drug that entered the systemic circulation. Our results also demonstrated that the BTFM had a certain affinity for keratin.

Conclusion: Our experimental results suggest that the BTFM may be an effective drug carrier for local skin therapy with good safety profile.
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http://dx.doi.org/10.2147/IJN.S270336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733396PMC
December 2020

Conditional reprograming culture conditions facilitate growth of lower grade glioma models.

Neuro Oncol 2020 Dec 1. Epub 2020 Dec 1.

Department of Pathology, Johns Hopkins University School of Medicine.

Background: The conditional reprogramming cell culture method was developed to facilitate growth of senescence-prone normal and neoplastic epithelial cells, and involves co-culture with irradiated fibroblasts and the addition of a small molecule Rho kinase (ROCK) inhibitor. The aim of this study was to determine whether this approach would facilitate the culture of compact low grade gliomas.

Methods: We attempted to culture 4 pilocytic astrocytomas, 2 gangliogliomas, 2 myxopapillary ependymomas, 2 anaplastic gliomas, 2 difficult-to-classify low grade neuroepithelial tumors, a desmoplastic infantile ganglioglioma, and an anaplastic pleomorphic xanthoastrocytoma using a modified conditional reprogramming cell culture approach.

Results: Conditional reprogramming resulted in robust increases in growth for a majority of these tumors, with fibroblast conditioned media and ROCK inhibition both required. Switching cultures to standard serum containing media, or serum free neurosphere conditions, with or without ROCK inhibition, resulted in decreased proliferation and induction of senescence markers. ROCK inhibition and conditioned media both promoted Akt and Erk1/2 activation. Several cultures, including one derived from a NF1-associated pilocytic astrocytoma (JHH-NF1-PA1) and one from a BRAF p.V600E mutant anaplastic pleomorphic xanthoastrocytoma (JHH-PXA1), exhibited growth sufficient for preclinical testing in vitro. In addition, JHH-NF1-PA1 cells survived and migrated in larval zebrafish orthotopic xenografts, while JHH-PXA1 formed orthotopic xenografts in mice histopathologically similar to the tumor from which it was derived.

Conclusions: These studies highlight the potential for the conditional reprogramming cell culture method to promote the growth of glial and glioneuronal tumors in vitro, in some cases enabling the establishment of long-term culture and in vivo models.
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http://dx.doi.org/10.1093/neuonc/noaa263DOI Listing
December 2020

Facile Synthesis of Ultrahigh Molecular Weight Poly(Methyl Methacrylate) by Organic Halides in the Presence of Palladium Nanoparticles.

Polymers (Basel) 2020 Nov 20;12(11). Epub 2020 Nov 20.

Institute of Industrial Catalysis, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China.

A facile and versatile approach for the synthesis of ultrahigh molecular weight poly(methyl methacrylate) (PMMA) at mild conditions was developed. Certain organic halides combined with a catalytical amount of palladium nanoparticles (Pd NPs) were found to be very effective in initiating polymerizations of methyl methacrylate (MMA), methyl acrylate, vinyl acetate and other vinyl monomers. An ultrahigh molecular weight PMMA with a number-average molecular weight of 4.65 × 10 Da and a weight-average molecular weight of 8.08 × 10 Da was synthesized at 70 °C using 2-bromoisobutyric acid ethyl ester (EBiB) as an initiator in the presence of catalytical amount (10.1 ppm) of Pd NPs. A kinetic investigation found that the orders of polymerization with respect to EBiB, Pd NP and MMA were 0.23, 0.50, and 0.58, respectively. Proton nuclear magnetic resonance (H NMR) combined with matrix-assisted laser desorption ionization time of flight mass spectroscopy (MALDI-TOF) and gel permeation chromatography (GPC) were used to prove that the macromolecular chain had an end-group of EBiB residue. The electron spin resonance (ESR), transmission electron microscope (TEM), and X-ray photoelectron spectroscopy (XPS) results reveal that the reaction of EBiB with Pd NPs caused a bromo atom (Br) transfer from EBiB to Pd NPs and resulted in the generation of EBiB residue radical to initiate the polymerization of MMA and the formation of PdBr on the surface of Pd nanoparticles.
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http://dx.doi.org/10.3390/polym12112747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699786PMC
November 2020

Hyperglycemia Induces Endoplasmic Reticulum Stress in Atrial Cardiomyocytes, and Mitofusin-2 Downregulation Prevents Mitochondrial Dysfunction and Subsequent Cell Death.

Oxid Med Cell Longev 2020 22;2020:6569728. Epub 2020 Oct 22.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China.

Mitochondrial oxidative stress and dysfunction play an important role of atrial remodeling and atrial fibrillation (AF) in diabetes mellitus. Endoplasmic reticulum (ER) stress has been linked to both physiological and pathological states including diabetes. The aim of this project is to explore the roles of ER stress in hyperglycemia-induced mitochondrial dysfunction and cell death of atrial cardiomyocytes. High glucose upregulated ER stress, mitochondrial oxidative stress, and mitochondria-associated ER membrane (MAM)- enriched proteins (such as glucose-regulated protein 75 (GRP75) and mitofusin-2 (Mfn2)) of primary cardiomyocytes . Sodium phenylbutyrate (4-PBA) prevented the above changes. Silencing of Mfn2 in HL-1 cells decreased the Ca transfer from ER to mitochondria under ER stress conditions, which were induced by the ER stress agonist, tunicamycin (TM). Electron microscopy data suggested that Mfn2 siRNA significantly disrupted ER-mitochondria tethering in ER stress-injured HL-1 cells. Mfn2 silencing attenuated mitochondrial oxidative stress and Ca overload, increased mitochondrial membrane potential and mitochondrial oxygen consumption, and protected cells from TM-induced apoptosis. In summary, Mfn2 plays an important role in high glucose-induced ER stress in atrial cardiomyocytes, and Mfn2 silencing prevents mitochondrial Ca overload-mediated mitochondrial dysfunction, thereby decreasing ER stress-mediated cardiomyocyte cell death.
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http://dx.doi.org/10.1155/2020/6569728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603626PMC
October 2020

Functional genetic variant of HSD17B12 in the fatty acid biosynthesis pathway predicts the outcome of colorectal cancer.

J Cell Mol Med 2020 12 28;24(24):14160-14170. Epub 2020 Oct 28.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Fatty acids are involved in the development and progression of colorectal cancer (CRC). However, genetic effects of fatty acid biosynthesis pathway on CRC outcome are unclear. Cox regression model was used to evaluate genetic effects on CRC overall survival (OS) and progression-free survival (PFS), accompanied by calculating hazard ratios (HRs) and confidence intervals (CIs). Differential expression analysis, expression quantitative trait loci analysis, dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to explore the genetically biological mechanism. The rs10838164 C>T in HSD17B12 was significantly associated with an increased risk of death and progression of CRC (OS, HR = 2.12, 95% CI = 1.40-3.22, P = 4.03 × 10 ; PFS, HR = 1.64, 95% CI = 1.11-2.44, P = 1.35 × 10 ), of which T allele could increase HSD17B12 expression (P = 1.78 × 10 ). Subsequently, the functional experiments indicated that rs10838164 T allele could not only enhance the binding affinity of transcription factor YY1 to HSD17B12 region harbouring rs10838164 but also promote the transcriptional activity of HSD17B12, which was significantly up-regulated in colorectal tumour tissues. Our findings suggest that genetic variants in fatty acid biosynthesis pathway play an important role in CRC outcome.
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http://dx.doi.org/10.1111/jcmm.16026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754038PMC
December 2020

Genetic variants in the Folic acid Metabolic Pathway Genes predict outcomes of metastatic Colorectal Cancer patients receiving first-line Chemotherapy.

J Cancer 2020 21;11(22):6507-6515. Epub 2020 Sep 21.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

The association between genetic variants in the folic acid metabolic pathway genes and survival, as well as the responses to chemotherapy of metastatic colorectal cancer (mCRC) patients has not been reported. The association between genetic variants in the folic acid metabolic pathway genes and progression-free survival (PFS) and overall survival (OS) of mCRC patients were analyzed using Cox regression model. The false discovery rate (FDR) correction method was conducted. The logistic regression model was used to explore the effects of the interested genetic variants on disease control rate (DCR). The Cancer Genome Atlas (TCGA) database was applied to compare gene expression differences. We found that rs3786362 G allele of thymidylate synthase () gene was significantly associated with PFS (P = 1.10 × 10), OS ( = 2.50 × 10) and DCR ( = 5.00 × 10). The expression of was overexpressed in CRC tissues compared with adjacent normal tissues. Furthermore, expression level decreased with respect to younger age and advanced tumor stage. Genetic variants in the folic acid metabolic pathway genes might serve as potential prognostic biomarkers for mCRC patients.
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http://dx.doi.org/10.7150/jca.44580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545690PMC
September 2020

Vascular and Microvascular Dysfunction Induced by Microgravity and Its Analogs in Humans: Mechanisms and Countermeasures.

Front Physiol 2020 20;11:952. Epub 2020 Aug 20.

Clinical Research Center, CHU d'Angers, Angers, France.

Weightlessness and physical inactivity have deleterious cardiovascular effects. The space environment and its ground-based models offer conditions to study the cardiovascular effects of physical inactivity in the absence of other vascular risk factors, particularly at the macro- and microcirculatory levels. However, the mechanisms involved in vascular dysfunction and remodeling are not sufficiently studied in the context of weightlessness and its analogs including models of physical inactivity. Here, we summarize vascular and microvascular changes induced by space flight and observed in models of microgravity and physical inactivity and review the effects of prophylactic strategies (i.e., countermeasures) on vascular and microvascular function. We discuss physical (e.g., exercise, vibration, lower body negative pressure, and artificial gravity) and nutritional/pharmacological (e.g., caloric restriction, resveratrol, and other vegetal extracts) countermeasures. Currently, exercise countermeasure appears to be the most effective to protect vascular function. Although pharmacological countermeasures are not currently considered to fight vascular changes due to microgravity, nutritional countermeasures are very promising. Dietary supplements/natural health products, especially plant extracts, should be extensively studied. The best prophylactic strategy is likely a combination of countermeasures that are effective not only at the cardiovascular level but also for the organism as a whole, but this strategy remains to be determined.
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http://dx.doi.org/10.3389/fphys.2020.00952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468431PMC
August 2020

Effects of Ultrasonic-Assisted Extraction on the Yield and the Antioxidative Potential of Triterpenes.

Molecules 2020 Sep 11;25(18). Epub 2020 Sep 11.

College of Life Science, Sichuan Agricultural University, Ya'an 625014, China.

This study was the first designed to evaluate the extraction and antioxidant ability of triterpenes from rhizomes. The yield of triterpenes from was mainly affected by the concentration of ethanol, followed by the extraction time, solvent to sample ratio, and the power of ultrasound. Thus, the response surface method was applied to investigate the interaction between the two factors and to optimize the extraction process. The optimal extraction conditions were 210 W, 75% ethanol, 40 min and 25 mL/g with a maximum yield of 229.37 ± 7.16 mg UAE/g. Moreover, the antioxidant ability of triterpenes from (TBE) was evaluated by determining the scavenging capacity on free radicals and the protection on CHO cells and against oxidative stress. The results showed the triterpenes could clear 2,2-Diphenyl-1-picryl-hydrazyl (DPPH) radicals well and had a strong reducing power. In addition, the survival of CHO cells was higher than that of the control group as a result of reducing the reactive oxygen species (ROS) level and promoting the activities of antioxidant enzymes. In addition, TBE could also enhance the survival of under HO conditions. Therefore, triterpenes from could be developed into a beneficial potential for antioxidants.
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http://dx.doi.org/10.3390/molecules25184159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570829PMC
September 2020

Detection of aflatoxin B with a new label-free fluorescent aptasensor based on exonuclease I and SYBR Gold.

Anal Methods 2020 06;12(22):2928-2933

College of Food Science and Engineering, Jilin Agricultural University, Changchun, 130118, China.

This paper describes a new label-free fluorescent aptasensor for the detection of aflatoxin B1 (AFB1) based upon exonuclease I (Exo I) and SYBR Gold, in which SYBR Gold, aptamer, AFB1, and Exo I were used. Specific combinations of aptamer and AFB1 occurred in the presence of AFB1 and consequently altered the spatial structure of the aptamer, thereby preventing its digestion by Exo I. When SYBR Gold was added, intense fluorescence was observed. Additionally, a good linear relationship was observed under optimized conditions between the fluorescence intensities and the AFB1 concentrations (R2 = 0.993). The established aptamer sensor was highly sensitive and exhibited a low limit of detection of 1.82 ng mL-1, with superior specificity for AFB1. It was also used in the quantification of AFB1 levels in soybean sauce samples and demonstrated satisfactory recoveries in the scope of 94.8-108.9%. The proposed sensor is highly sensitive, low cost, and capable of rapid detection and can thus be used to determine mycotoxin levels in a wide range of feeds and food products in a high-throughput and quantitative means.
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http://dx.doi.org/10.1039/d0ay00967aDOI Listing
June 2020

Organoplatinum(II)-Based Self-Complementary Molecular Tweezers with Guest-Induced Fluorochromic Behaviors.

Inorg Chem 2020 Oct 13;59(19):14134-14140. Epub 2020 Sep 13.

CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.

Cyclometalated organoplatinum(II) complexes have aroused tremendous interests due to their square-planar geometry and intriguing photophysics. To access multiplatinum systems with more than three cyclometalated organoplatinum(II) units, the traditional covalent synthetic approach suffers from tedious multistep reactions with low overall yield. In comparison, supramolecular assembly can be regarded as an effective strategy toward multiplatinum(II) architectures. Despite the progresses achieved, it is still challenging to fabricate well-ordered supramolecular assemblies with precise numbers of organoplatinum(II) units. Herein, self-complementary dimerized molecular tweezers with four cyclometalated platinum(II) units have been successfully constructed by taking advantage of dual roles of the incorporated 2,2':6',2''-terpyridine unit (serving as the rigid spacer and encapsulated guest). Furthermore, addition of electron-rich carbazoles leads to conversion of the self-complementary structure to molecular tweezer/guest complexes. Such a structural transformation gives rise to the concomitant luminescent color change. The unique guest-induced fluorochromic phenomena, which are seldom reported in the previous host-guest systems, would be promising as tunable luminescent and ratiometric sensing materials.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01899DOI Listing
October 2020

Development of Environmentally Friendly Atom Transfer Radical Polymerization.

Polymers (Basel) 2020 Aug 31;12(9). Epub 2020 Aug 31.

Institute of Industrial Catalysis, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China.

Atom transfer radical polymerization (ATRP) is one of the most successful techniques for the preparation of well-defined polymers with controllable molecular weights, narrow molecular weight distributions, specific macromolecular architectures, and precisely designed functionalities. ATRP usually involves transition-metal complex as catalyst. As the most commonly used copper complex catalyst is usually biologically toxic and environmentally unsafe, considerable interest has been focused on iron complex, enzyme, and metal-free catalysts owing to their low toxicity, inexpensive cost, commercial availability and environmental friendliness. This review aims to provide a comprehensive understanding of iron catalyst used in normal, reverse, AGET, ICAR, GAMA, and SARA ATRP, enzyme as well as metal-free catalyst mediated ATRP in the point of view of catalytic activity, initiation efficiency, and polymerization controllability. The principle of ATRP and the development of iron ligand are briefly discussed. The recent development of enzyme-mediated ATRP, the latest research progress on metal-free ATRP, and the application of metal-free ATRP in interdisciplinary areas are highlighted in sections. The prospects and challenges of these three ATRP techniques are also described in the review.
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http://dx.doi.org/10.3390/polym12091987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563397PMC
August 2020

Xanthine oxidase inhibitor allopurinol improves atrial electrical remodeling in diabetic rats by inhibiting CaMKII/NCX signaling.

Life Sci 2020 Oct 18;259:118290. Epub 2020 Aug 18.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China. Electronic address:

Aims: Atrial fibrillation (AF) is a common arrhythmia which is associated with higher risk of stroke, heart failure and all-cause mortality. Abnormal Ca handling in diabetes mellitus (DM) can cause delayed depolarization involved with increased NCX activity. Complicated mechanisms are involved in atrial remodeling, of which CaMKII may be a key node signal. Therefore, we intend to explore whether CaMKII activation induces atrial electrical remodeling by regulating NCX expression in this study.

Main Methods: Adult male SD rats were used to establish a diabetic rat model, divided into three groups: the control group, DM group and allopurinol group. Hemodynamic and ECG indicators were recorded, after which electrophysiological studies were conducted. The protein expression of CaMKII, p-CaMKII, XO, MnSOD and NCX was measured by Western blot and immunohistochemistry. H&E and Masson staining were applied for observing myocardial fibrosis. HL-1 cells were cultured for the measurement of ROS generation.

Key Findings: The arrangement of atrial myocytes was disordered and the collagen volume fraction of the atrium tissue was elevated in the DM group compared with the control group, and improved by allopurinol. Higher incidence of inducible AF, reduced conduction velocity and higher conduction inhomogeneity were observed in diabetic rats. These electrophysiological abnormalities were accompanied by higher oxidative stress and protein expression of p-CaMKII and NCX. Allopurinol prevented the development of these abnormal changes.

Significance: Allopurinol can improve atrial electrical remodeling by inhibiting CaMKII activity and protein expression of NCX. These data indicate xanthine oxidase inhibition can reduce oxidative stress and ameliorate atrial electrical remodeling.
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http://dx.doi.org/10.1016/j.lfs.2020.118290DOI Listing
October 2020

The efficacy of medical treatment for adenomyosis after adenomyomectomy.

J Obstet Gynaecol Res 2020 Oct 28;46(10):2092-2099. Epub 2020 Jul 28.

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China.

Aims: To compare the efficacy of gonadotropin-releasing hormone agonist (GnRH-a) and GnRH-a + levonorgestrel-releasing intrauterine system (LNG-IUS) after adenomyomectomy for improved adenomyosis-associated symptoms.

Methods: Overall, 193 patients with adenomyosis included in this study were categorized into three groups: adenomyomectomy (n = 57, group 1), adenomyomectomy + GnRH-a (n = 83, group 2) and adenomyomectomy + GnRH-a + LNG-IUS (n = 53, group 3). Visual Analog Scale (VAS) scores and uterine volumes were determined to evaluate the severity of adenomyosis. Dysmenorrhea improvement and uterine volume were the main outcomes.

Results: The VAS scores of all patients reduced from 7.3 (6.0, 8.5) to 0 (0, 0.6) at the 6 months after surgery, which were significantly higher in group 1 compared to other groups (P < 0.05). In groups 1, 2 and 3, there were 14, 7 and 4 patients, respectively, who suffered dysmenorrhea recurrence. The mean recurrent-free-survival (RFS) was 51.6 ± 2.4, 58.0 ± 1.2 and 58.3 ± 1.0 months, respectively, which was significantly shorter in group 1 (P < 0.05). The dysmenorrhea recurrences were 26.3%, 6.1%, 5.9% in groups 1, 2 and 3, respectively, at the 36 months, which was significantly higher in group 1 (P < 0.01). Significantly decreased uterine volumes were observed in all patients from 222.2 (147.6, 350.4) to 77.0 (65.9, 94.1) mL (P < 0.05) at the 6 month after surgery.

Conclusion: Treatment GnRH-a and LNG-IUS after surgery could significantly reduce the recurrence and prolong the RFS. It seemed that the use of LNG-IUS was beneficial for a lower recurrence in long-term follow-up.
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http://dx.doi.org/10.1111/jog.14376DOI Listing
October 2020

Selenium Enhances Cadmium Accumulation Capability in Two Mustard Family Species- and .

Plants (Basel) 2020 Jul 17;9(7). Epub 2020 Jul 17.

College of Life Science, Sichuan Agricultural University, Chengdu 611130, China.

Oilseed rape () is a Cadmium (Cd) hyperaccumulator. However, high-level Cd at the early seedling stage seriously arrests the growth of rape, which limits its applications. had higher Cd accumulation capacity, but its biomass was lower, also limiting its applications. Previous studies have confirmed that Selenium (Se) can alleviate Cd toxicity. However, the regulatory mechanism of Se in different valence states of Cd accumulation was unclear. In this study, we investigated the ameliorating effects of three Se valence states, NaSeO [Se(VI)], NaSeO [Se(IV)] and Se-Met [Se(II)], to Cd toxicity by physiological and biochemical approaches in hydroponically-cultured and seedlings. Although Se treatments slightly inhibited seedling Cd concentration, it tripled or quadrupled the Cd accumulation level per plant, because dry weight increased about four times more with Se and Cd application than with Cd treatment alone. Among the different valence states of Se, Se(II) had the most marked effect on reducing Cd toxicity as evidenced by decreased growth inhibition and Cd content. The application of Se(II) was effective in reducing Cd-induced reactive oxygen species accumulation, and promoted the antioxidant enzyme activity and photosynthesis of both species. In addition, Se(II) treatment increased the concentrations of Cd in the cell wall and soluble fractions, but the Cd concentration in the organelle part was reduced.
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http://dx.doi.org/10.3390/plants9070904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412126PMC
July 2020

Rapid and sensitive detection of Mycobacterium tuberculosis based on strand displacement amplification and magnetic beads.

Luminescence 2021 Feb 6;36(1):66-72. Epub 2020 Aug 6.

School of Chemistry, Biology and Material Science, ECUT, Nanchang, China.

Tuberculosis is one of the main infectious diseases threatening public health, and the development of simple, rapid, and cost-saving methods for tuberculosis diagnosis is of profound importance for tuberculosis prevention and treatment. The bacterium Mycobacterium tuberculosis (MTB) is the pathogen that causes tuberculosis, and assaying for MTB is the only criterion for tuberculosis diagnosis. A new enzyme-free method based on strand displacement amplification and magnetic beads was developed for simple, rapid, and cost-saving MTB detection. Under optimum conditions, a good linear relationship could be observed between fluorescence and MTB specific DNA concentration ranging from 0.05 to 150 nM with a correlation coefficient of 0.993 (n = 8) and a detection limit of 47 pM (3σ/K). The present method also distinguished a one base mismatch from MTB specific DNA, showing great promise for MTB genome single base polymorphism analysis. MTB specific DNA content in polymerase chain reaction samples was successfully detected using the new method, and recoveries were 97.8-100.8%, indicating that the present method had high accuracy and shows good potential for the early diagnosis of tuberculosis.
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http://dx.doi.org/10.1002/bio.3918DOI Listing
February 2021

Effects of steel slag amendments on accumulation of cadmium and arsenic by rice (Oryza sativa) in a historically contaminated paddy field.

Environ Sci Pollut Res Int 2020 Nov 10;27(32):40001-40008. Epub 2020 Jul 10.

School of Environment and Tourism, West Anhui University, Lu'an, 237012, China.

Paddy soil contamination by cadmium (Cd) and arsenic (As) is a great concern. Field experiments were conducted to study the effects of steel slag (SS, 2.0 and 4.0 t ha) on the solubility of Cd and As in soil and their accumulation by rice plants grown in a historically co-contaminated paddy field with Cd and As. The results showed that SS amendment (4.0 t ha) significantly decreased soluble concentrations of Cd in pore-water but increased that of As, related to markedly elevated soil pH and soluble silicon, phosphorus of pore-water in rice rhizosphere at both heading and mature stages. The amendments also evidently decreased Cd but enhanced As in iron plaque on root surfaces, while the formation of iron plaque was not significantly increased. Further, SS amendment (4.0 t ha) markedly reduced Cd concentrations in rice tissues (roots, straw, and brown rice) by 48-78% at both stages, though increased As by 13-38%. Cadmium translocation from roots to aerial parts decreased significantly after the amendments, but not for As. Besides, SS application increased the biomass of roots, straw and grains, and root antioxidant enzyme activities. Collectively, steel slag decreased Cd accumulation in rice tissues and in iron plaque but increased those of As, likely due to steel slag decreasing soluble Cd and enhancing soluble As in pore-water, related to soil pH and soluble nutrients (Si, P), and restraining Cd translocation within rice. Our results indicate that steel slag represents a favorable potential for Cd-contaminated paddy soils, though it seems undesirable for Cd and As co-contamination.
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http://dx.doi.org/10.1007/s11356-020-10028-3DOI Listing
November 2020

Phenolic Composition, Antioxidant and Anticancer Potentials of Extracts from Ait. Flowers.

Molecules 2020 Jul 6;25(13). Epub 2020 Jul 6.

College of Life Science, Sichuan Agricultural University, Ya'an 625014, China.

Ait. () is a traditional Chinese folk medicine and an ornamental plant. Most previous studies have focused on cultivation and utilization while there are few research papers on the pharmacological activity of . This study aimed to get a better understanding of by extracting polyphenols with fractionated extraction technology. The results showed that ethyl acetate phase (EAP) contained the most polyphenols, while water phase (WP) had the least. HPLC analysis indicated that rutin and luteolin-4'--glucoside existed in the EAP and butanol phase (BP), but quercetin was only detected in the EAP. Six phenolic compositions were not detected in WB. The antioxidant and anti-tumor abilities of the EAP and BP were excellent. The results revealed that possessed a great antioxidant capacity and was rich in polyphenols, thus indicating was suitable for being a natural antioxidant and an abundant source of polyphenols.
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http://dx.doi.org/10.3390/molecules25133068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411795PMC
July 2020

Inhibition of complement pathway activation with Pozelimab, a fully human antibody to complement component C5.

PLoS One 2020 8;15(5):e0231892. Epub 2020 May 8.

Regeneron Pharmaceuticals, Inc., New York, NY, United States of America.

Complement is a key component of the innate immune system. Inappropriate complement activation underlies the pathophysiology of a variety of diseases. Complement component 5 (C5) is a validated therapeutic target for complement-mediated diseases, but the development of new therapeutics has been limited by a paucity of preclinical models to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) properties of candidate therapies. The present report describes a novel humanized C5 mouse and its utility in evaluating a panel of fully human anti-C5 antibodies. Surprisingly, humanized C5 mice revealed marked differences in clearance rates amongst a panel of anti-C5 antibodies. One antibody, pozelimab (REGN3918), bound C5 and C5 variants with high affinity and potently blocked complement-mediated hemolysis in vitro. In studies conducted in both humanized C5 mice and cynomolgus monkeys, pozelimab demonstrated prolonged PK and durable suppression of hemolytic activity ex vivo. In humanized C5 mice, a switch in dosing from in-house eculizumab to pozelimab was associated with normalization of serum C5 concentrations, sustained suppression of hemolytic activity ex vivo, and no overt toxicity. Our findings demonstrate the value of humanized C5 mice in identifying new therapeutic candidates and treatment options for complement-mediated diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231892PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209288PMC
July 2020

The aerobic respiratory chain of Pseudomonas aeruginosa cultured in artificial urine media: Role of NQR and terminal oxidases.

PLoS One 2020 23;15(4):e0231965. Epub 2020 Apr 23.

Department of Biological Sciences, Illinois Institute of Technology, Chicago, IL, United States of America.

Pseudomonas aeruginosa is a Gram-negative γ-proteobacterium that forms part of the normal human microbiota and it is also an opportunistic pathogen, responsible for 30% of all nosocomial urinary tract infections. P. aeruginosa carries a highly branched respiratory chain that allows the colonization of many environments, such as the urinary tract, catheters and other medical devices. P. aeruginosa respiratory chain contains three different NADH dehydrogenases (complex I, NQR and NDH-2), whose physiologic roles have not been elucidated, and up to five terminal oxidases: three cytochrome c oxidases (COx), a cytochrome bo3 oxidase (CYO) and a cyanide-insensitive cytochrome bd-like oxidase (CIO). In this work, we studied the composition of the respiratory chain of P. aeruginosa cells cultured in Luria Broth (LB) and modified artificial urine media (mAUM), to understand the metabolic adaptations of this microorganism to the growth in urine. Our results show that the COx oxidases play major roles in mAUM, while P. aeruginosa relies on CYO when growing in LB medium. Moreover, our data demonstrate that the proton-pumping NQR complex is the main NADH dehydrogenase in both LB and mAUM. This enzyme is resistant to HQNO, an inhibitory molecule produced by P. aeruginosa, and may provide an advantage against the natural antibacterial agents produced by this organism. This work offers a clear picture of the composition of this pathogen's aerobic respiratory chain and the main roles that NQR and terminal oxidases play in urine, which is essential to understand its physiology and could be used to develop new antibiotics against this notorious multidrug-resistant microorganism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231965PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179901PMC
July 2020

Luteolin attenuates sepsis‑induced myocardial injury by enhancing autophagy in mice.

Int J Mol Med 2020 May 11;45(5):1477-1487. Epub 2020 Mar 11.

Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

Sepsis‑induced cardiomyopathy (SIC) is a complication of severe sepsis and septic shock characterized by an invertible myocardial depression. This study sought to explore the potential effects and mechanism of luteolin, a flavonoid polyphenolic compound, in lipopolysaccharide (LPS)‑induced myocardial injury. Experimental mice were randomly allocated into 3 groups (25 mice in each group): The control group (NC), the LPS group (LPS) and the LPS + luteolin group (LPS + Lut). Before the SIC model was induced, luteolin was dissolved in DMSO and injected intraperitoneally for 10 days into LPS + Lut group mice. NC group and LPS group mice received an equal volume of DMSO for 10 days. On day 11, the animal model of sepsis‑induced cardiac dysfunction was induced by intraperitoneal injection of LPS. A total of 12 h after LPS injection, measurements and comparisons were made among the groups. Luteolin administration improved cardiac function, attenuated the inflammatory response, alleviated mitochondrial injury, decreased oxidative stress, inhibited cardiac apoptosis and enhanced autophagy. In addition, luteolin significantly decreased the phosphorylation of AMP‑activated protein kinase (AMPK) in septic heart tissue. The protective effect of luteolin was abolished by 3‑methyladenine (an autophagy inhibitor) and dorsomorphin (compound C, an AMPK inhibitor), as evidenced by decreased autophagic activity, destabilized mitochondrial membrane potential and increased apoptosis in LPS‑treated cardiomyocytes, but was mimicked by 5‑aminoimidazole‑4‑carboxamide ribonucleotide (an AMPK activator), suggesting that luteolin attenuates LPS‑induced myocardial injury by increasing autophagy through AMPK activation. Luteolin may be a promising therapeutic agent for treating SIC.
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http://dx.doi.org/10.3892/ijmm.2020.4536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138288PMC
May 2020