Publications by authors named "Wenjuan Xu"

142 Publications

Rapid, label-free, and sensitive point-of-care testing of anti-SARS-CoV-2 IgM/IgG using all-fiber Fresnel reflection microfluidic biosensor.

Mikrochim Acta 2021 07 19;188(8):261. Epub 2021 Jul 19.

School of Environment and Natural Resources, Renmin University of China, Beijing, 100872, China.

The ongoing global pandemic of SARS-CoV-2 has promoted to develop novel serological testing technologies since they can be effectively complementary to RT-PCR. Here, a new all-fiber Fresnel reflection microfluidic biosensor (FRMB) was constructed through combining all-fiber optical system, microfluidic chip, and multimode fiber bio-probe. The transmission of the incident light and the collection and transmission of Fresnel reflection light are achieved using a single-multi-mode fiber optic coupler (SMFC) without any other optical separation elements. This compact design greatly simplifies the whole system structure and improves light transmission efficiency, which makes it suitable for the label-free, sensitive, and easy-to-use point-of-care testing (POCT) of targets in nanoliter samples. Based on Fresnel reflection mechanism and immunoassay principle, both the SARS-CoV-2 IgM and IgG antibodies against the SARS-CoV-2 spike protein could be sensitively quantified in 7 min using the secondary antibodies-modified multimode fiber bio-probe. The FRMB performs in one-step, is accurate, label-free, and sensitive in situ/on-site detection of SARS-CoV-2 IgM or IgG in serum with simple dilution only. The limits of detection of SARS-CoV-2 IgM and SARS-CoV-2 IgG were 0.82 ng/mL and 0.45 ng/mL, respectively. Based on our proposed theory, the affinity constants of SARS-CoV-2 IgM or IgG antibody and their respective secondary antibodies were also determined. The FRMB can be readily extended as a universal platform for the label-free, rapid, and sensitive in situ/on-site measurement of other biomarkers and the investigation of biomolecular interaction.
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http://dx.doi.org/10.1007/s00604-021-04911-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286882PMC
July 2021

Hydrogen Sulfide Contributes to Uterine Quiescence Through Inhibition of NLRP3 Inflammasome Activation by Suppressing the TLR4/NF-κB Signalling Pathway.

J Inflamm Res 2021 25;14:2753-2768. Epub 2021 Jun 25.

Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Background: The NLRP3 inflammasome plays a critical role in inflammatory responses in various diseases. Our previous study showed that NLRP3 expression was significantly increased in human pregnancy tissue during term labour. Therefore, we explored whether NLRP3 participated in inflammatory responses of preterm and term labour and whether this process could be relieved by HS, one anti-inflammatory gasotransmitter.

Methods: Human myometrium was obtained from non-labouring and labouring women. Mouse myometrium was obtained from LPS-induced infectious preterm labour. Uterine smooth muscle cells were isolated from non-labouring women's myometrial tissues, transfected with siRNA, and treated cells with IL-1β, HS donor NaHS, NF-κB inhibitor BAY 11-7082 and TLR4 inhibitorTAK-242. The NLRP3 inflammasome, CSE, CBS, TLR4, uterine contraction-associated proteins (CAPs), NF-κB activation and inflammatory cytokine expression were assessed by Western blotting and RT-PCR.

Results: The NLRP3 inflammasome, TLR4 and activated NF-κB expression were upregulated in human term labour, mouse preterm labour and human uterine smooth muscle cells treated with IL-1β. NLRP3 levels were negatively correlated with CSE and CBS expression. Treatment with the HS donor NaHS delayed LPS-induced preterm birth in mice and inhibited NLRP3 inflammasome activation. In siNLRP3-transfected cells, there was a significant decrease in the expression of CAPs and inflammatory cytokines compared with IL-1β stimulation. In addition, treatment with the HS donor NaHS inhibited NLRP3 inflammasome activation, reduced the expression of uterine contraction-associated proteins and inflammatory cytokines and reduced the activation of TLR4 and NF-κB compared with stimulation with IL-1β in human uterine smooth muscle cells. Furthermore, treatment of uterine smooth muscle cells with BAY 11-7082 and TAK-242 found that NLRP3 activation was regulated by the TLR4 and NF-κB pathways.

Conclusion: HS suppresses CAP expression and the inflammatory response and contributes to uterine quiescence by inhibiting the TLR4/NF-κB signalling pathway and downstream NLRP3 inflammasome activation. Thus, HS contributes to uterine quiescence through inhibition of NLRP3 inflammasome activation by suppressing the TLR4/NF-κB signalling pathway.
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http://dx.doi.org/10.2147/JIR.S308558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242154PMC
June 2021

High Proton Conductivity in Nafion/Ni-MOF Composite Membranes Promoted by Ligand Exchange under Ambient Conditions.

Inorg Chem 2021 Jul 2;60(14):10492-10501. Epub 2021 Jul 2.

The College of Chemistry and Green Catalysis Center, Zhengzhou University, Zhengzhou, Henan 450001, P. R. China.

Metal-organic frameworks (MOFs) have appeared to be promising competitive candidates as crystalline porous materials for proton conduction. Explorations of the method of preparation of proton conductive MOFs and the proton transfer mechanism have enabled them to attract widespread attention, and tremendous efforts have been made to improve the proton conductivity of MOFs. On the basis of our previous work, we explicitly propose that ligand exchange can upgrade the proton conduction performance of MOFs. Using MOF-azo as the precursor, the proton conductivities of exchange products MOF-bpy and MOF-bpe increase by 3.5- and 2.8-fold, respectively. After the MOFs had been doped into the Nafion matrix to prepare composite membranes, the proton conduction performance of composite membranes filled with subproducts (2.6 × 10 and 1.95 × 10 S cm) is significantly better than that of a composite membrane filled with a parent product (1.12 × 10 S cm) under ambient conditions (without heating or humidifying). The ligand exchange strategy presented herein demonstrates great promise for the development of high-proton conductivity MOFs and MOF composites with expanded future applications.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01107DOI Listing
July 2021

Network analysis of potential risk genes for psoriasis.

Hereditas 2021 Jun 16;158(1):21. Epub 2021 Jun 16.

Department of Dermatology, General Hospital of Xinjiang Military Command, No. 359 Youhao North Road, Saybak District, Urumqi, 830001, Xinjiang, China.

Background: Psoriasis is a complex chronic inflammatory skin disease. The aim of this study was to analyze potential risk genes and molecular mechanisms associated with psoriasis.

Methods: GSE54456, GSE114286, and GSE121212 were collected from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between psoriasis and controls were screened respectively in three datasets and common DEGs were obtained. The biological role of common DEGs were identified by enrichment analysis. Hub genes were identified using protein-protein interaction (PPI) networks and their risk for psoriasis was evaluated through logistic regression analysis. Moreover, differentially methylated positions (DMPs) between psoriasis and controls were obtained in the GSE115797 dataset. Methylation markers were identified after comparison with the common genes.

Results: A total of 118 common DEGs were identified, which were mainly involved in keratinocyte differentiation and IL-17 signaling pathway. Through PPI network, we identified top 10 degrees as hub genes. Among them, high expression of CXCL9 and SPRR1B may be risk factors for psoriasis. In addition, we selected 10 methylation-modified genes with the higher area under receiver operating characteristic curve (AUC) value as methylation markers. Nomogram showed that TGM6 and S100A9 may be associated with an increased risk of psoriasis.

Conclusion: This suggests that immune and inflammatory responses are active in keratinocytes of psoriatic skin. CXCL9, SPRR1B, TGM6 and S100A9 may be potential targets for the diagnosis and treatment of psoriasis.
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http://dx.doi.org/10.1186/s41065-021-00186-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210373PMC
June 2021

The outer membrane protein Amuc_1100 of Akkermansia muciniphila alleviates the depression-like behavior of depressed mice induced by chronic stress.

Biochem Biophys Res Commun 2021 Aug 12;566:170-176. Epub 2021 Jun 12.

School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China. Electronic address:

Akkermansia muciniphila is a symbiotic intestinal bacterium with a high medicinal value. Amuc_1100 is the outer membrane protein of A. muciniphila and plays an important role in the interaction between A. muciniphila and its host. The objective of this study was to evaluate the antidepressant activity of Amuc_1100 in a chronic unpredictable mild stress (CUMS) model. Amuc_1100 intervention ameliorated CUMS-induced depression-like behavior and CUMS-induced down-regulation of serotonin (5-hydroxytryptamine, or simply, 5-HT) in the serum and colon of mice. Microbial analysis of mouse feces showed that Amuc_1100 could improve the gut microbiota dysregulation induced by CUMS. In addition, Amuc_1100 intervention could also improve the down-regulation of brain-derived neurotrophic factor (BDNF) and inflammation in the hippocampus induced by CUMS. These results suggest that Amuc_1100 has a good antidepressant effect, and the mechanism may be related to the improvement of gut microbiota, the up-regulation of the BDNF level, and the inhibition of the neuroinflammatory response.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.018DOI Listing
August 2021

Exploring the synergistic mechanism of Gegen Qinlian Decoction on the Wnt signaling pathway using an integrated strategy of network pharmacology and RNA-seq.

J Ethnopharmacol 2021 Oct 30;278:114283. Epub 2021 Jun 30.

School of Life Sciences, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China. Electronic address:

Ethnopharmacological Relevance: Gegen Qinlian Decoction (GQD) (including: Puerariae lobatae (Willd.) Ohwi, radix; (short for Gengen) Glycyrrhiza uralensis Fisch., root and rhizome (short for Gancao), honeyed; Coptis chinensis Franch., rhizome (short for Huanglian); Scutellaria baicalensis Georgi, radix, boiled (short for S. baicalensis) has been widely used to treat inflammatory bowel disease (IBD) and colorectal cancer (CRC). To explore compatibility mechanism of GQD could be of advantage to investigate the complex principle of TCM, which might be conducive to the exploration of the modernization of TCM.

Aim Of Review: In this study, a strategy based on system pharmacology was constructed to uncover the multi-target regulation and compatibility mechanism of GQD on the Wnt signaling pathways.

Material And Methods: The pharmacological network of GQD was constructed by TCMSP, DAVID, Uniprote database. The cell growth inhibitory effects of puerarin (PUE), wogonin (WOG), berberine (BER), and glycyrrhetinic acid (GLY) on SW480 cells were assessed using CCK-8 assay. The multi-target regulation and compatibility mechanism of combination PUE with GLY were examined by RNA-seq, HPLC-QQQ/MS, qRT- PCR and Western blot analysis.

Results: Network pharmacology analysis indicated that PUE, WOG, BER and GLY were the active components in GQD and had a synergistic effect on the targets of the Wnt signaling pathway. Additionally, pharmacological experiments revealed that WOG, BER, and GLY inhibited activity of colorectal cancer (CRC) cell lines SW480 cells, and that PUE only exhibited effective antitumour activity when combined with GLY. CTNNB1, CCND1 and SMAD4 were identified as synergistic targets inhibited by PUE-GLY. Moreover, PUE-GLY could influence the Wnt signaling pathway by upregulating GSK3B and downregulating CTNNB1 synergistically. It also showed that GLY could effectively increase the intracellular content of PUE based on HPLC-QQQ/MS analysis, and this process was achieved by influencing the targets of the membrane's pathway, such as cell adhesion molecules, focal adhesion, and tight junctions.

Conclusion: GLY was revealed a multi-target mechanism, which could downregulate CTNNB1 as the active component and intervene in membrane proteins (CDH1, CADM1, ITGB2, ICAM1, ITGA1) as 'guide' in the formulae. Moreover, the mechanism of synergistic antitumour action of PUE (the active component of Monarch drug) and GLY (the active component of Guide drug) on the Wnt signaling pathway was explored systematically. It was a promising breakthrough for elucidating the scientific connotation of the compatibility of TCM formulae and provide a valuable and practicable methodology for clarifying the mechanisms of TCM.
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http://dx.doi.org/10.1016/j.jep.2021.114283DOI Listing
October 2021

IMCC: A Novel Quantitative Approach Revealing Variation of Global Modular Map and Local Inter-Module Coordination Among Differential Drug's Targeted Cerebral Ischemic Networks.

Front Pharmacol 2021 16;12:637253. Epub 2021 Apr 16.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

Stroke is a common disease characterized by multiple genetic dysfunctions. In this complex disease, detecting the strength of inter-module coordination (genetic community interaction) and subsequent modular rewiring is essential to characterize the reactive biosystematic variation (biosystematic perturbation) brought by multiple-target drugs, whose effects are achieved by hitting on a series of targets (target profile) jointly. Here, a quantitative approach for inter-module coordination and its transition, named as IMCC, was developed. Applying IMCC to mouse cerebral ischemia-related gene microarray, we investigated a holistic view of modular map and its rewiring from ischemic stroke to drugs (baicalin, BA; ursodeoxycholic acid, UA; and jasminoidin, JA) perturbation states and locally identified the cooperative pathological module pair and its dissection. Our result suggested the global modular map in cerebral ischemia exhibited a characteristic "core-periphery" architecture, and this architecture was rewired by the effective drugs heterogeneously: BA and UA converged modules into an intensively connected integrity, whereas JA diverged partial modules and widened the remaining inter-module paths. Locally, the PMP dissociation brought by drugs contributed to the reversion of the pathological condition: the focus of the cellular function shift from survival after nervous system injury into development and repair, including neurotrophin regulation, hormone releasing, and chemokine signaling activation. The core targets and mechanisms were validated by experiments. Overall, our result highlights the holistic inter-module coordination rearrangement rather than a target or a single module that brings phenotype alteration. This strategy may lead to systematically explore detailed variation of inter-module pharmacological action mode of multiple-target drugs, which is the principal problem of module pharmacology for network-based drug discovery.
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http://dx.doi.org/10.3389/fphar.2021.637253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087074PMC
April 2021

The outer membrane protein Amuc_1100 of promotes intestinal 5-HT biosynthesis and extracellular availability through TLR2 signalling.

Food Funct 2021 Apr;12(8):3597-3610

School of Life Sciences, Anhui University, Hefei 230601, Anhui, China. and Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China.

Akkermansia muciniphila is a probiotic inhabiting host intestinal mucus layers and displays evident easing or therapeutic effects on host enteritis and metabolic disorders such as obesity and diabetes. The outer membrane protein Amuc_1100 of A. muciniphila is likely to play a crucial role during the interaction with the host. 5-HT is a neurotransmitter and a key signal molecule regulating the gastrointestinal tract functions and other organs, which is involved in diverse physiological and pathological processes. This study demonstrated that Amuc_1100 could promote the expression of the 5-HT synthesis rate-limiting enzyme Tph1 in RIN-14B cells and reduce the expression of the serotonin reuptake transporter (SERT) in Caco-2 cells through direct interaction with TLR2, thereby improving 5-HT biosynthesis and extracellular availability. Using antibiotic-treated mice as animal models, we found that after gavage with A. muciniphila or Amuc_1100, Tph1 expression increased and SERT expression decreased in colon tissues. The 5-HT concentrations in colon tissues and blood were markedly elevated simultaneously. We also found that A. muciniphila or Amuc_1100 improved the gastrointestinal motility function and restored gut microbiota abundance and species diversity in antibiotic-treated mice. These results suggest that A. muciniphila can regulate the host intestinal 5-HT system via its outer membrane protein Amuc_1100 and TLR2. This mechanism represented an important approach through which A. muciniphila interacts with the host and further influences 5-HT-related physiological functions. These results advance the understanding of interplay mechanisms between the gut microbiota and the host, which could be the basis for new intervention strategies for related diseases.
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http://dx.doi.org/10.1039/d1fo00115aDOI Listing
April 2021

Influence of a Substituted Methyl on the Photoresponsive Third-Order Nonlinear-Optical Properties Based on Azobenzene Metal Complexes.

Inorg Chem 2021 May 26;60(10):7240-7249. Epub 2021 Apr 26.

College of Chemistry and Green Catalysis Center, Zhengzhou University, Zhengzhou, Henan 450001, P. R. China.

For studying the effect of a substituted group on the photoresponsive third-order nonlinear-optical (NLO) properties, photosensitive azobenzene derivative was first selected to construct metal complexes {[Zn(L1)(HO)]·2DMA)} () and {[Cd(L1)(4,4'-bpy)HO]·HO} (). Then with a substituted methyl on the azobenzene ring was used to construct complexes {[Zn(L2)(4,4'-bpy)(HO)]} () and {[Cd(L2)(4,4'-bpy)(HO)]} (). When the azobenzene moiety of the complexes is trans, the NLO behaviors of the complexes are the same. However, after the azobenzene moiety is excited by ultraviolet (UV) light to change from trans to cis, the substituted methyl increases the repulsion between two azobenzene rings in and , thereby affecting their NLO behaviors. Therefore, the nonlinearity of the two types of complexes is different after UV irradiation. Density functional theory calculations support this result. The substituted methyl has a significant influence on the nonlinear absorption behaviors of and . This work not only reports the examples of photoresponsive NLO materials based on metal complexes but also provides a new idea to deeply explore NLO properties.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00331DOI Listing
May 2021

Growth hormone protects against ovarian granulosa cell apoptosis: Alleviation oxidative stress and enhancement mitochondrial function.

Reprod Biol 2021 Jun 8;21(2):100504. Epub 2021 Apr 8.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei, 230032, Anhui, China. Electronic address:

Growth hormone (GH) is a polypeptide hormone that could reduce the mitochondria-mediated oxidative stress and improve the mitochondrial function. However, the mechanisms of GH on granulosa cell apoptosis and mitochondrial function is still unclear. The aim of this study is to determine the effects of GH on granulosa cells apoptosis and the underlying mechanisms. In this study, we exposed the ovarian granulosa cell line (KGN cell) with cisplatin to establish an ovarian granulosa cell apoptosis and mitochondrial dysfunction model in vitro. To examine the benefit of GH in restoration of granulosa cell, we determined cell proliferation, cell apoptosis, reactive oxygen species (ROS) level, the expression of antioxidant components Sod2, Sirt3, as well as the mitochondrial membrane potential and mitochondrial DNA (mtDNA) copy number after GH treatment. We found that the cisplatin exposure significantly inhibited cell proliferation and elevated the apoptotic rate by student's t-test (p < 0.05). Whereas, the GH treatment could rescue the cell proliferation and decrease the apoptotic rate, as well as reduce the Bax/Bcl-2 ratio (p < 0.05). Additionally, GH significantly reduced abnormal ROS levels and increased the level of Sirt3 and Sod2 thus alleviating the oxidative stress. We also found that GH facilitated the recovery of mitochondrial membrane potential and mitochondrial DNA (mtDNA) copy number in granulosa cells. Our results indicated that GH exerted protective effects in cisplatin-induced ovarian granulosa cell apoptosis by alleviating oxidative stress and enhancing mitochondrial function via Sirt3-Sod2 pathway.
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http://dx.doi.org/10.1016/j.repbio.2021.100504DOI Listing
June 2021

Ginkgolide B Maintains Calcium Homeostasis in Hypoxic Hippocampal Neurons by Inhibiting Calcium Influx and Intracellular Calcium Release.

Front Cell Neurosci 2020 10;14:627846. Epub 2021 Feb 10.

Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Command, Urumqi, China.

Ginkgolide B (GB), a terpene lactone and active ingredient of , shows protective effects in neuronal cells subjected to hypoxia. We investigated whether GB might protect neurons from hypoxic injury through regulation of neuronal Ca homeostasis. Primary hippocampal neurons subjected to chemical hypoxia (0.7 mM CoCl) exhibited an increase in cytoplasmic Ca (measured from the fluorescence of fluo-4), but this effect was significantly diminished by pre-treatment with 0.4 mM GB. Electrophysiological recordings from the brain slices of rats exposed to hypoxia revealed increases in spontaneous discharge frequency, action potential frequency and calcium current magnitude, and all these effects of hypoxia were suppressed by pre-treatment with 12 mg/kg GB. Western blot analysis demonstrated that hypoxia was associated with enhanced mRNA and protein expressions of Ca1.2 (a voltage-gated Ca channel), STIM1 (a regulator of store-operated Ca entry) and RyR2 (isoforms of Ryanodine Receptor which mediates sarcoplasmic reticulum Ca release), and these actions of hypoxia were suppressed by GB. Taken together, our and data suggest that GB might protect neurons from hypoxia, in part, by regulating Ca influx and intracellular Ca release to maintain Ca homeostasis.
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http://dx.doi.org/10.3389/fncel.2020.627846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928385PMC
February 2021

Prevalence and outcome of young stroke patients with middle cerebral artery stenosis.

BMC Neurol 2021 Mar 4;21(1):99. Epub 2021 Mar 4.

Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Neuroimmunology, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, 250014, China.

Background: Etiologies of acute ischemic stroke in young adults are heterogeneous. Middle cerebral artery (MCA) stenosis is a common finding in Asians which may be an important cause of stroke in young adults. However, studies of stroke in young Asian populations are rare. Our study was to investigate the prevalence and outcome of young stroke patients with MCA stenosis in Chinese populations.

Methods: Young patients with MCA territory infarction between January 2013 and September 2018 were retrospectively recruited. Subjects were defined as stenosis group (MCA stenosis ≥50%) and no-stenosis group (MCA stenosis<50% or no stenosis) by their MCA stenosis. For patients in stenosis group, they were categorized as uni-MCA stenosis subgroup and multiple stenosis subgroup. Demographic data, risk factors, imaging feature and complications were compared between groups. Prevalence of MCA stenosis and risk factor score (score ≥ 2 or 3) in different age groups were investigated. Modified Rankin Scale (mRS) was used for evaluating functional outcome at discharge (unfavorable outcome: 3-6). Binary logistic regression was performed to determine independent risk factors of unfavorable outcome.

Results: Two hundred forty-nine young stroke patients were included in our study and 110 (44.2%) patients were defined as stenosis group. 55 (50%) patients were categorized as uni-MCA stenosis subgroup and 55 (50%) were multiple stenosis subgroup. The most common traditional vascular risk factors included hypertension, hyperlipemia, smoking, hyperhomocysteinemia and alcohol consumption. Prevalence of risk factor score ≥ 2 or 3 increased with age, but not incidence of MCA stenosis. By TOAST classification, the most common etiologies were large-artery atherosclerosis (41.0%) and small vessel disease (33.7%). Compared with no-stenosis group, patients in stenosis group were more likely to have large territorial infarct, develop complications and have unfavorable outcome. No significant difference was found between patients in uni-MCA stenosis and multiple stenosis subgroups except history of stroke/TIA, risk factor score ≥ 3 and silent infarct. By logistic regression, hypertension (OR = 3.561; 95%CI, 1.494 to 8.492; p = 0.004), NIHSS scores at admission (OR = 1.438; 95%CI, 1.276 to 1.620; p = 0,000) and infarct size (p = 0.015) independently predicted unfavorable outcome.

Conclusions: Forty-four point two percent young Chinese adults with MCA territory infarction had MCA stenosis. Prevalence of MCA stenosis did not increase with age. Patients with MCA stenosis had worse clinical outcome, however, only hypertension, NIHSS scores at admission and infarct size were independent predictors.
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http://dx.doi.org/10.1186/s12883-021-02125-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931598PMC
March 2021

Preparation, structure characterization, and specific gut microbiota properties related to anti-hyperlipidemic action of type 3 resistant starch from Canna edulis.

Food Chem 2021 Jul 20;351:129340. Epub 2021 Feb 20.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, No.11 North 3rd Ring East Road, Chao-Yang District, Beijing 100029, China; Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Chao-Yang District, Beijing 100029, China. Electronic address:

Type 3 resistant starch (RS3) was developed from Canna edulis (Ce) native starch (NS) through dual enzymatic hydrolysis and recrystallization. Thereafter, the processed Ce-RS3 was subjected to systematic characterizations for its structural properties, anti-hyperlipidemic effect, and in vivo gut microbiota modulatory function. The Ce-RS3 content was increased to 49.11% after processing under optimal conditions. Compared with NS, Ce-RS3 maintained its B-type crystallization without introducing new chemical groups. Meanwhile, it displayed coarse surfaces, higher crystallinity, more ordered structures, and a higher proportion of chains with degree of polymerization (DP) 37-100. Ce-RS3 intervention significantly alleviated dyslipidemia in hyperlipidemic mice, which was associated with increased gut microbial diversity and unique microbial enrichment, potentially mediated by its fine structure. These observations are valuable for developing RS3 from C. edulis for prebiotics applications and support the potential strategy that utilizes well-designed RS to modulate specific bacterial populations to improve health.
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http://dx.doi.org/10.1016/j.foodchem.2021.129340DOI Listing
July 2021

Amuc_1102 from Akkermansia muciniphila adopts an immunoglobulin-like fold related to archaeal type IV pilus.

Biochem Biophys Res Commun 2021 Apr 14;547:59-64. Epub 2021 Feb 14.

School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China; Institute of Physical Science, Institute of Information Technology, Anhui University, Hefei, Anhui, 230601, China. Electronic address:

Akkermansia muciniphila is a kind of beneficial microorganism colonized in the human gut. A. muciniphila is closely related to human intestinal health and has a good effect on diseases related to intestinal metabolism. The proteins encoded by the Amuc_1098-Amuc_1102 gene cluster, which are related to the formation and assembly of the pilus, are highly expressed in the membrane protein components of A. muciniphila. In this paper, we report the crystal structure of Amuc_1102 at a resolution of 1.75 Å, which adopts an immunoglobulin (Ig)-like fold. Amuc_1102 shares a similar fold to three archaeal proteins related to type IV pilus (T4P)-like structure, Pilin, FlaF, and FlaG, indicating a similar function. Amuc_1102 exists as a trimer both in the crystal structure and in solution, which differs from the assemblies of Pilin, FlaF, and FlaG. This study provides a structural basis for the elucidation of the T4P formation of A. muciniphila.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.022DOI Listing
April 2021

Primary and secondary metabolites produced in Salvia miltiorrhiza hairy roots by an endophytic fungal elicitor from Mucor fragilis.

Plant Physiol Biochem 2021 Mar 21;160:404-412. Epub 2021 Jan 21.

School of Chinese Materia, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address:

Salvia miltiorrhiza is one of the most commonly used medicinal materials in China. In recent years, the quality of S. miltiorrhiza has attracted much attention. Biotic and abiotic elicitors are widely used in cultivation to improve the quality of medicinal plants. We isolated an endophytic fungus, Mucor fragilis, from S. miltiorrhiza. We compared the effects of endophytic fungal elicitors with those of yeast extract together with silver ion, widely used together as effective elicitors, on S. miltiorrhiza hairy roots. Seventeen primary metabolites (amino acids and fatty acids) and five secondary metabolites (diterpenoids and phenolic acids) were analyzed after elicitor treatment. The mycelium extract promoted the accumulation of salvianolic acid B, rosmarinic acid, stearic acid, and oleic acid in S. miltiorrhiza hairy roots. Additionally, qPCR revealed that elicitors affect the accumulation of primary and secondary metabolites by regulating the expression of key genes (SmAACT, SmGGPPS, and SmPAL). This is the first detection of both the primary and secondary metabolites of S. miltiorrhiza hairy roots, and the results of this work should help guide the quality control of S. miltiorrhiza. In addition, the findings confirm that Mucor fragilis functions as an effective endophytic fungal elicitor with excellent application prospect for cultivation of medicinal plants.
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http://dx.doi.org/10.1016/j.plaphy.2021.01.023DOI Listing
March 2021

Proton Conduction of Nafion Hybrid Membranes Promoted by NH-Modified Zn-MOF with Host-Guest Collaborative Hydrogen Bonds for H/O Fuel Cell Applications.

ACS Appl Mater Interfaces 2021 Feb 5;13(6):7485-7497. Epub 2021 Feb 5.

The College of Chemistry and Green Catalysis Center, Zhengzhou University, Zhengzhou, Henan 450001, P. R. China.

It is of great significance to develop creative proton exchange membrane materials for proton exchange membrane fuel cells (PEMFCs). The strategy of doping metal-organic frameworks (MOFs) with guest molecules into the Nafion matrix is adopted to improve the electrochemical performance of Nafion hybrid membranes. Various and abundant hydrogen bonds can make a tremendous contribution to the proton conduction of hybrid membranes. In this work, we used high proton-conducting Zn-MOFs with the characteristics of host-guest collaborative hydrogen bonds as the filler to prepare Zn-MOF/Nafion hybrid membranes. Alternating current (AC) impedance tests show that when the doping amount of Zn-MOF is 5%, the proton conductivity reaches 7.29 × 10 S·cm, being 1.87 times that of the pure Nafion membrane at 58% relative humidity (RH) and 80 °C. In an attempt to prove the promotion effect of guest NH on proton conductivity of Nafion hybrid membranes, Zn-MOF-NH was filled into the Nafion matrix. Under the same conditions, its proton conductivity reaches the maximum value of 2.13 × 10 S·cm, which is 5.47 times that of the pure Nafion membrane. Zn-MOF-NH/Nafion-5 was used to fabricate a proton exchange membrane for application in H/O fuel cells. The maximum power density of 212 mW cm and a current density of 630 mA cm reveal a respectable single cell performance. This study provides a promising method for optimizing the structure of MOF proton conductors and inspires the preparation of high-performance Nafion hybrid membranes.
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http://dx.doi.org/10.1021/acsami.0c21840DOI Listing
February 2021

Postsynthetic-Modified PANI/MOF Composites with Tunable Thermoelectric and Photoelectric Properties.

Chemistry 2021 Mar 19;27(15):5011-5018. Epub 2021 Feb 19.

The College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China.

A 3D Co-based metal-organic framework (Co-MOF) with two kinds of large pores filled by free Co ions and ligands was synthesized and characterized. To expand the MOF structure and conductivity, the free Co ions and ligands were exchanged by conductive ionic liquid EtpyBr and photosensitive AgNO through single crystal-to-single crystal transformation, which produced structure-changed 3D MOFs Co-MOF-Br and Co-Ag-MOF, which were characterized by single-crystal X-ray diffraction. Incorporating small quantities of doped polyaniline (PANI) with redox activity into the pores could further tune the stability and conductivity of the three MOFs. The PANI/MOFs all show outstanding electrical conductivity (≈10  S cm ), and PANI/Co-MOF-Br has the largest p-type Seebeck coefficient of 66.6 μV K . PANI/Co-MOF-Br and PANI/Co-Ag-MOF have 4 and 15 times higher photocurrent density compared with PANI/Co-MOF, respectively. This work sheds light on the design of advanced electrically conductive 3D MOFs.
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http://dx.doi.org/10.1002/chem.202005474DOI Listing
March 2021

A new insulin-sensitive enhancer from Silene viscidula, WPTS, treats type 2 diabetes by ameliorating insulin resistance, reducing dyslipidemia, and promoting proliferation of islet β cells.

Pharmacol Res 2021 03 4;165:105416. Epub 2021 Jan 4.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, China; Beijing Institute of Chinese Medicine, Beijing University of Chinese Medicine, China. Electronic address:

Wacao pentacyclic triterpenoid saponins (WPTS) is a newly discovered insulin sensitivity enhancer. It is a powerful hypoglycemic compound derived from Silene viscidula, which has a hypoglycemic effect similar to that of insulin. It can rapidly reduce blood glucose levels, normalizing them within 3 days of administration. However, its mechanism of action is completely different from that of insulin. Thus, we aimed to determine the pharmacological effects and mechanism of activity of WPTS on type 2 diabetes to elucidate the main reasons for its rapid effects. The results showed that WPTS could effectively improve insulin resistance in KKAy diabetic mice. Comparative transcriptomics showed that WPTS could upregulate the expression of insulin resistance-related genes such as glucose transporter type 4 (Glut4), insulin receptor substrate 1 (Irs1), Akt, and phosphoinositide 3-kinase (PI3K), and downregulate the expression of lipid metabolism-related genes such as monoacylglycerol O-acyltransferase 1 (Moat1), lipase C (Lipc), and sphingomyelin phosphodiesterase 4 (Smpd4). The results indicated that the differentially expressed genes could regulate lipid metabolism via the PI3K/AKT metabolic pathway, and it is noteworthy that WPTS was found to upregulate Glut4 expression, decrease blood glucose levels, and attenuate insulin resistance via the PI3K/AKT pathway. Q-PCR and western blotting further validated the transcriptomics findings at the mRNA and protein levels, respectively. We believe that WPTS can achieve a rapid hypoglycemic effect by improving the lipid metabolism and insulin resistance of the diabetic KKAy mice. WPTS could be a very promising candidate drug for the treatment of diabetes and deserves further research.
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http://dx.doi.org/10.1016/j.phrs.2020.105416DOI Listing
March 2021

Effects of Rearing Conditions and Sex on Cecal Microbiota in Ducks.

Front Microbiol 2020 8;11:565367. Epub 2020 Oct 8.

Jiangsu Institute of Poultry Science, Yangzhou, China.

The intestinal microbiome influences the health of animals. However, little is known about the impact of indoor conditions and sex on intestinal microbiome diversity and composition in ducks. The present study aimed to investigate differences in the cecal microbiome between male and female ducks reared on the floor (PY group) or in cages (LY group). We also determined the relationships between cecal microbiota composition and slaughter traits, and the expression levels of mucosal and intestinal structural genes in ducks. There was a slight difference in slaughter traits among the groups, with cecum weight being significantly lighter in the LY compared with the PY group, especially in females ( < 0.05). Analysis of the alpha diversity of the cecal microbiota between males and females in the LY and PY groups showed that LY males had significantly lower diversity and richness. Beta diversity analysis demonstrated differences in the microbiota composition in relation to rearing conditions, and a significant difference between the sexes in the PY groups. The dominant bacterial phyla in duck cecum were Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. The relative abundances of the most common bacteria revealed that the intestinal microbiota diversity and composition were affected by both feeding conditions and sex. Several bacterial genera were detected differentially among the groups. These genera were correlated with slaughter traits and expression levels of mucosal and cecal structural genes in ducks. In conclusion, rearing conditions, sex, and associated changes in the cecal microbiota are thus associated with gut barrier functions in ducks.
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http://dx.doi.org/10.3389/fmicb.2020.565367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578374PMC
October 2020

Kupffer Cells: Inflammation Pathways and Cell-Cell Interactions in Alcohol-Associated Liver Disease.

Am J Pathol 2020 11 11;190(11):2185-2193. Epub 2020 Sep 11.

Research Service, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana; Indiana Center for Liver Research and Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address:

Chronic alcohol consumption is linked to the development of alcohol-associated liver disease (ALD). This disease is characterized by a clinical spectrum ranging from steatosis to hepatocellular carcinoma. Several cell types are involved in ALD progression, including hepatic macrophages. Kupffer cells (KCs) are the resident macrophages of the liver involved in the progression of ALD by activating pathways that lead to the production of cytokines and chemokines. In addition, KCs are involved in the production of reactive oxygen species. Reactive oxygen species are linked to the induction of oxidative stress and inflammation in the liver. These events are activated by the bacterial endotoxin, lipopolysaccharide, that is released from the gastrointestinal tract through the portal vein to the liver. Lipopolysaccharide is recognized by receptors on KCs that are responsible for triggering several pathways that activate proinflammatory cytokines involved in alcohol-induced liver injury. In addition, KCs activate hepatic stellate cells that are involved in liver fibrosis. Novel strategies to treat ALD aim at targeting Kupffer cells. These interventions modulate Kupffer cell activation or macrophage polarization. Evidence from mouse models and early clinical studies in patients with ALD injury supports the notion that pathogenic macrophage subsets can be successfully translated into novel treatment options for patients with this disease.
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http://dx.doi.org/10.1016/j.ajpath.2020.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587925PMC
November 2020

Role of the lncRNA-mRNA network in atherosclerosis using ox-low-density lipoprotein-induced macrophage-derived foam cells.

Mol Omics 2020 12 11;16(6):543-553. Epub 2020 Sep 11.

School of Life Science, Beijing University of Chinese Medicine, Northeast Corner of Intersection of Sunshine South Street and Baiyang East Road, Fang-Shan District, Beijing, 102488, China.

Atherosclerosis (AS) is the leading cause of coronary heart disease, cerebral infarction, peripheral vascular disease, and other cardiovascular diseases, making it a major risk factor for high morbidity and mortality. Although long non-coding RNAs (lncRNAs) have been reported to play a role in AS, the specific effects of lncRNAs on AS remain largely unknown. Thus the purpose of this study was to explore the roles of mRNAs and lncRNAs in atherosclerosis via an ox-low-density lipoprotein induced macrophage-derived foam cell model. Microarray analysis identified a total of 50 688 mRNAs and 1514 lncRNAs, including 51 lncRNAs and 1730 mRNAs that were significantly dysregulated in the model group (p-adjust < 0.05 and |log 2FC| > 2). The results of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that the dysregulated genes were associated with cell proliferation, cell apoptosis, and inflammatory responses. An lncRNA-mRNA co-expression network was created to further analyze the key regulatory genes. The lncRNAs Brip1os, Gm16586, AU020206, 9430034N14Rik, 2510016D11Rik, LNC_000709, Gm15472, Gm20703, and Dubr were identified as potential biomarkers in macrophage-derived foam cells. Based on 9 lncRNAs and 13 mRNAs, key genes influencing the degree of cell proliferation and cell apoptosis and the subsequent development of AS were identified. Q-PCR verified the key dysregulated genes. Thus, our results suggest potential therapeutic targets for AS and provide avenues for further research on AS pathogenesis.
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http://dx.doi.org/10.1039/d0mo00077aDOI Listing
December 2020

Structural and biochemical analyses of β-N-acetylhexosaminidase Am0868 from Akkermansia muciniphila involved in mucin degradation.

Biochem Biophys Res Commun 2020 09 28;529(4):876-881. Epub 2020 Jul 28.

School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China. Electronic address:

β-N-acetylhexosaminidases from the gut microbes are found to be capable of cleaving the specific glycoside linkages in the process of mucin degradation that has relevance for human health. However, features of the enzyme used in regulating the sugar-degrading capacities of Akkermansia muciniphila have not been well defined. Here we reported the crystal structure of a novel β-N-acetylhexosaminidase from Akkermansia muciniphila (Am0868), which displayed a typical (β/α) barrel fold with a GlcNAc bound to the active center. Crystallographic and subsequent mutagenic analyses confirmed that Asp326 and Glu327 are the key catalytic residues of Am0868. Furthermore, Am0868 exhibited high specificity to β-GlcNAc supporting the substrate-assisted catalytic mechanism. Am0868 was also active in a broad pH and temperature range but inhibited strongly by metal ions Zn and Cu. Collectively, these results indicate that Am0868 has the potential for mucin hydrolysis under some severe conditions, which highlight the superiority of A. muciniphila surviving in gut.
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http://dx.doi.org/10.1016/j.bbrc.2020.06.116DOI Listing
September 2020

Aster tataricus attenuates asthma efficiently by simultaneously inhibiting tracheal ring contraction and inflammation.

Biomed Pharmacother 2020 Oct 9;130:110616. Epub 2020 Aug 9.

Beijing Key Laboratory of Syndrome Prescription Basic Research, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address:

Asthma is an airway chronic inflammatory disease with significant morbidity, mortality and huge social economic burden. Previous research demonstrated that the root of Aster tataricus (RA) may have the potential to treat asthma, but the efficacy and mechanism were not clear. In this study, preliminary results in vitro showed that Fr-75 eluted from RA extract could not only completely inhibit the tracheal ring contraction raised by KCl in 20 min, but also effectively affect the tracheal ring contraction induced by KCl-, Ach- and His in a concentration-dependent manner (3.91-250 μg/mL). Further results on cells exhibited that Fr-75 could decrease the concentration of intracellular Ca as well. These results revealed the underlying mechanism in vitro that the inhibition of tracheal ring contraction might be due to the decline of the intracellular Ca concentration, which caused by suppressing calcium channel, antagonizing the muscarinic and histamine receptors. Also, results in vivo exhibited that Fr-75 could distinctly ease the symptoms of ovalbumin-sensitized mice, including relieving the pathological injury, increasing the latency to preconvulsive dyspnea and to enhanced pause, reducing the inflammatory cells, chemokines and cytokines in BALF and lung tissue. In general, it could be speculated that RA fraction may attenuate asthma through dilating the tracheal ring contraction and alleviating the lung inflammation simultaneously.
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http://dx.doi.org/10.1016/j.biopha.2020.110616DOI Listing
October 2020

Reusable optofluidic point-of-care testing platform with lyophilized specific antibody for fluorescence detection of cholylglycine in serum.

Mikrochim Acta 2020 07 11;187(8):439. Epub 2020 Jul 11.

School of Environment and Natural Resources, Renmin University of China, Beijing, 100874, China.

A reusable optofluidic point-of-care testing platform (OPOCT) was successfully constructed through integrating evanescent wave fluorescence technology into an all-fiber-based optofluidic system. The compact design of the OPOCT allows it to be portable and suitable for on-site sensitive determination of biomarkers in serum without complicated and costly procedures. The sensitivity of 90.9 pM for antibody determination is observed thanks to the high transmission efficiency of excitation light and fluorescence in the OPOCT. The affinity constant between cholylglycine (CG) and anti-CG antibody was quantified using this platform based on the proposed theory. Using the lyophilized fluorescence-labeled specific antibody and reusable fiber optic biosensor, the OPOCT is applied to the one-step sensitive determination of CG in serum, which eliminates the dearth associated with liquid reagent handling, disposable biosensors, and user intervention. A limit of detection of 0.025 μg/mL for CG is obtained, which is far more than adequate for meeting diagnostic requirements. The matrix effect of serum samples on the evanescent wave-based optofluidic biosensor can be effectively reduced by simple dilution of serum samples. The performance of the OPOCT also compared favorably with that of a commercial turbidimetric inhibition immunoassay through analyzing multiple serum samples. This platform is ready to expand to measure any other biomarker by using its specific antibody. The simplicity, sensitivity, cost-effectiveness, and robustness of the OPOCT enable the early diagnosis of disease and making a timely clinical decision. Graphical abstract .
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http://dx.doi.org/10.1007/s00604-020-04424-2DOI Listing
July 2020

infection affects intestinal barrier structure and immune reactions in the duck caecum.

Avian Pathol 2020 Dec 4;49(6):572-580. Epub 2020 Aug 4.

Department of Waterfowl Breeding and Production, Jiangsu Institute of Poultry Science, Yangzhou, People's Republic of China.

(RA) infection causes high mortality and poor feed conversion, leading to great economic losses to the duck industry. This study investigated the effects of RA on the intestinal morphology and immune response of ducks. Histological examination showed that RA infection caused intestinal injury, including significantly reduced mucosal thickness on days 2, 3 and 5, significantly reduced villus height on days 1, 2, 3 and 5 ( < 0.05) and significantly reduced villus height to crypt depth ratios on days 2, 3, 5 and 9 of RA infection ( < 0.05). The expression of intestinal mucosal layer construction-associated genes and tight junction genes was significantly altered on at least one time point (day 1, 2, 3, 5, 9 or 14) after RA infection. Quantitative real-time polymerase chain reaction revealed that RA infection affected intestinal mucosal immune function. The genes encoding TLR4 (toll like receptor-4), TRAF6 (TNF receptor-associated factor 6), MYD88 (myeloid differentiation factor 88), IFN-γ (interferon-γ), IL (interleukin)-4 and IL-8 were significantly upregulated on day 2 of RA infection. Taken together, these results indicate that RA infection negatively affects intestinal barrier function in ducks due to impaired mucosal and villus-crypt structure and alters the mRNA expression of mucous layer construction-, intestinal tight junction-, and intestinal mucosal immunity-related genes.
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http://dx.doi.org/10.1080/03079457.2020.1792414DOI Listing
December 2020

Increased miR-223-3p in Leukocytes Positively Correlated with IL-17A in Plasma of Asthmatic Patients.

Iran J Allergy Asthma Immunol 2020 Jun 23;19(3):289-296. Epub 2020 Jun 23.

Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

Asthma is a common airway inflammation with an intricate underlying mechanism. The role played by circulating miRNAs in asthma remains unclear. In the present study, we aimed to investigate the role of miR-223-3p in leukocytes of asthma and identify the relationship between miR-223-3p and inflammatory cytokines in asthma. Using real-time polymerase chain reaction (RT-PCR), we detected miR-223-3p expression in peripheral blood leukocytes from 23 asthmatic patients and 20 healthy controls. The levels of IFN-γ (Th1 cytokine), IL-4 (Th2 cytokine), IL-17A (Th17 cytokine) in plasma were examined using enzyme-linked immunosorbent assay (ELISA). Analysis of variance (ANOVA) and Spearman's test was used for statistical analysis. The expression of miR-223-3p in peripheral blood leukocytes was upregulated in the asthmatic patients compared with that in the healthy controls. Increased miR-223-3p expression was associated with forced expiratory volume in 1-second percent predicted (FEV1% predicted). A positive correlation was noted between miR-223-3p and IL-17A. The findings of this study showed that miR-223-3p plays a vital role in the pathogenesis of asthma and can serve as a novel biomarker for asthma.
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http://dx.doi.org/10.18502/ijaai.v19i3.3456DOI Listing
June 2020

Intervention of resistant starch 3 on type 2 diabetes mellitus and its mechanism based on urine metabonomics by liquid chromatography-tandem mass spectrometry.

Biomed Pharmacother 2020 Aug 7;128:110350. Epub 2020 Jun 7.

Beijing University of Chinese Medicine, Northeast Corner of Intersection of Sunshine South Street and Baiyang East Road, Fang-Shan District, Beijing, 102488, China. Electronic address:

As a severe metabolic disease, type 2 diabetes mellitus (T2DM) has aroused increasing public attentions. Resistant starch 3 (RS3), as a starch resistant to enzymatic hydrolysis owing to its special structure, has a good effect on improving insulin resistance and reducing blood sugar in T2DM patients. However, the possible mechanisms were barely interpreted yet. In our research, we aimed to evaluate the effects and the possible mechanisms of RS3 on the treatment of T2DM. ICR mice treated with high-fat diet (HFD) for eight weeks, and then injected with streptozotocin (STZ) (100 mg/kg) to establish the T2DM. We choose the mice with the fast blood glucose (FBG) more than 11 mmol/L as T2DM. After treated for 11 weeks the relevant data was analyzed. According to the results, the FBG was dramatically reduced (p < 0.05), which also downregulated triglyceride (p < 0.01) and total cholesterol (p < 0.01). Additionally, the insulin resistance indexes were significantly reduced (p < 0.01), the homeostasis model assessment-β and insulin-sensitive index were significantly improved (p < 0.01) in RS3 group. Meanwhile, the metabolic profiles of urine were analyzed and 29 potential biomarkers were screened out, including amino acids and lipids. In conclusion, we speculated that the tricarboxylic acid cycle, amino acid metabolism and lipid metabolism played roles in the therapeutic mechanisms of RS3 on T2DM.
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http://dx.doi.org/10.1016/j.biopha.2020.110350DOI Listing
August 2020

A specific gut microbiota and metabolomic profiles shifts related to antidiabetic action: The similar and complementary antidiabetic properties of type 3 resistant starch from Canna edulis and metformin.

Pharmacol Res 2020 09 3;159:104985. Epub 2020 Jun 3.

School of Chinese Meteria Medica, Beijing University of Chinese Medicine, Northeast Corner of Intersection of Sunshine South Street and Baiyang East Road, Fang-Shan District, Beijing, 102488, China. Electronic address:

The relationship between gut microbiota and type 2 diabetes mellitus (T2DM) has drawn increasing attention, and the benefits of various treatment strategies, including nutrition, medication and physical exercise, maybe microbially-mediated. Metformin is a widely used hypoglycemic agent, while resistant starch (RS) is a novel dietary fiber that emerges as a nutritional strategy for metabolic disease. However, it remains unclear as to the potential degree and interactions among gut microbial communities, metabolic landscape, and the anti-diabetic effects of metformin and RS, especially for a novel type 3 resistant starch from Canna edulis (Ce-RS3). In the present study, T2DM rats were administered metformin or Ce-RS3, and the changes in gut microbiota and serum metabolic profiles were characterized using 16S-rRNA gene sequencing and metabolomics, respectively. After 11 weeks of treatment, Ce-RS3 exhibited similar anti-diabetic effects to those of metformin, including dramatically reducing blood glucose, ameliorating the response to insulin resistance and glucose tolerance test, and relieving the pathological damage in T2DM rats. Interestingly, the microbial and systemic metabolic dysbiosis in T2DM rats was effectively modulated by both Ce-RS3 and, to a lesser extent, metformin. The two treatments increased the gut bacterial diversity, and supported the restoration of SCFA-producing bacteria, thereby significantly increasing SCFAs levels. Both treatments simultaneously corrected 16 abnormal metabolites in the metabolism of lipids and amino acids, many of which are microbiome-related. PICRUSt analysis and correlation of SCFAs levels with metabolomics data revealed a strong association between gut microbial and host metabolic changes. Strikingly, Ce-RS3 exhibited better efficacy in increasing gut microbiota diversity with a peculiar enrichment of Prevotella genera. The gut microbial properties of Ce-RS3 were tightly associated with the T2DM-related indexes, showing the potential to alleviate diabetic phenotype dysbioses, and possibly explaining the greater efficiency in improving metabolic control. The beneficial effects of Ce-RS3 and metformin might derive from changes in gut microbiota through altering host-microbiota interactions with impact on the host metabolome. Given the complementarity of Ce-RS3 and metformin in regulation of gut microbiota and metabolites, this study also prompted us to suggest possible "Drug-Dietary fiber" combinations for managing T2DM.
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http://dx.doi.org/10.1016/j.phrs.2020.104985DOI Listing
September 2020

The 50-Fold Enhanced Proton Conductivity Brought by Aqueous-Phase Single-Crystal-to-Single-Crystal Central Metal Exchange.

Inorg Chem 2020 Jun 26;59(12):8361-8368. Epub 2020 May 26.

The College of Chemistry, Zhengzhou University, Zhengzhou, Henan 450001, P. R. China.

Coordination polymer {[CoL(HO)]·2HO} goes through aqueous-phase single-crystal-to-single-crystal (SC-SC) central metal exchange to produce {[CuL(HO)]·2HO}. The daughter product presents a higher proton conductivity of 0.004 S cm at 95 °C and 100% RH, increasing by 50-fold relative to the parent product. The water vapor adsorption reveals that the uptake capacity of reaches 145.08 mg/g, which is 7.5 times that of (19.36 mg/g). High water affinity is confirmed by the smaller water contact angle of . Replacing water vapor with vapors of dilute hydrochloric acid and ammonia, the improvement of proton conductivity is also realized. Exchanged products all give enhanced conductivities in different vapor atmospheres, which shows that the aqueous-phase central metal exchange is a judicious choice for the preparation of excellent proton conducting coordination polymers.
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http://dx.doi.org/10.1021/acs.inorgchem.0c00766DOI Listing
June 2020

Role of Arginase in Selective Impairment of Endothelium-Dependent Nitric Oxide Synthase-Mediated Dilation of Retinal Arterioles during Early Diabetes.

Invest Ophthalmol Vis Sci 2020 05;61(5):36

.

Purpose: Retinal vasomotor activity can be regulated by two major endothelial enzymes, nitric oxide synthase (NOS) and cyclooxygenase (COX). The vascular arginase also consumes a NOS substrate and thus impedes NOS-mediated vasodilation. Diabetes mellitus exhibits vascular complications in the retina with elevated oxidative stress and compromised NOS-mediated vasodilation. However, the underlying molecular mechanisms remain unclear, and the effect of diabetes on COX-mediated vasodilation is unknown. Herein, we examined the relative impact of diabetes on retinal arteriolar dilations to COX and NOS activation and the roles of arginase and superoxide in diabetes-induced vasomotor dysfunction.

Methods: Retinal arterioles were isolated from streptozocin-induced diabetic pigs (2 weeks of hyperglycemia, 433 ± 27 mg/dL) or age-matched control pigs (97 ± 4 mg/dL). The vasodilations to bradykinin (NOS activator) and histamine (NOS/COX activator) were examined in vitro.

Results: Retinal arteriolar dilations to histamine and bradykinin were significantly reduced after 2 weeks of diabetes. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) attenuated the dilations of control vessels, but not diabetic vessels, to histamine. In the presence of L-NAME and COX inhibitor indomethacin, histamine-induced dilations of control and diabetic vessels were reduced similarly. Treatment of diabetic vessels with arginase inhibitor nor-NOHA, but not superoxide dismutase mimetic TEMPOL, preserved both histamine- and bradykinin-induced dilations in an L-NAME-sensitive manner.

Conclusions: Arginase, rather than superoxide, impairs endothelium-dependent NOS-mediated dilation of retinal arterioles during diabetes, whereas vasodilation mediated by COX remains intact. Blockade of vascular arginase may improve endothelial function of retinal arterioles during early onset of diabetes.
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http://dx.doi.org/10.1167/iovs.61.5.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405695PMC
May 2020
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