Publications by authors named "Meng Pan"

166 Publications

A Case of Annular Epidermolytic Ichthyosis Resulting from a de Novo Mutation, p.I479T, in Gene.

Indian J Dermatol 2021 Mar-Apr;66(2):224

Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

We report a case of annular epidermolytic ichthyosis (AEI) resulting from gene mutation. AEI is a rare autosomal dominantly inherited cornification disorder and is a distinct phenotypic variant of bullous congenital ichthyosiform erythroderma. Blisters and erosions in AEI are widespread; hence, initially, it is sometimes mistaken with epidermolysis bullosa, acrodermatitis enteropathica, and staphylococcal scalded skin syndrome. Genetic tests including next-generation sequencing and Sanger sequencing are essential for AEI diagnosis. AEI is treated symptomatically by wound dressing, prevention of infection, and the use of emollients, humectants, and keratolytic products; topical or systemic retinoids may also prove helpful.
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http://dx.doi.org/10.4103/ijd.IJD_115_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208282PMC
June 2021

Activation of Hippocampal IR/IRS-1 Signaling Contributes to the Treatment with Zuogui Jiangtang Jieyu Decoction on the Diabetes-Related Depression.

Evid Based Complement Alternat Med 2021 3;2021:6688723. Epub 2021 Jun 3.

Key Laboratory of Chinese Material Medical Power and Innovation Drugs Established By Provincial and Ministry, Hunan University of Chinese Medicine, Changsha, Hunan, China.

Background: Zuogui Jiangtang Jieyu decoction (ZJJ) is mainly used for the treatment of diabetes-related depression in current clinical applications and research. This study aims to investigate whether the brain IR/IRS-1 signaling pathway is involved in the therapeutic effect of ZJJ on depression-like behavior in diabetic rats.

Methods: Sprague-Dawley rats were fed with high-fat diet and subjected to streptozotocin injection to establish the diabetes animal model. After treatment with different doses of ZJJ (20.530 g/kg or 10.265 g/kg) for 4 weeks, the blood glucose level and peripheral insulin resistance were measured. The forced-swimming test (FST) and Morris water maze test (MWMT) were applied for the mood and cognitive function assessment. Then, the Western blot method was used to analyze the protein levels of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylonositol-3-kinase (PI3K), and protein kinase B (PKB, also as known as AKT) in the hippocampus of diabetic rats. Meanwhile, the immunofluorescence method was performed to analyze the above proteins' expression in the neuron and astrocyte. At last, the levels of glycogen, lactate, and ATP were tested by the ELISA method. Additionally, the insulin-sensitive glucose transporter 4 (GLUT4) and the lactate transporter monocarboxylate transporter 4 (MCT4) were analyzed by the Western blot method.

Results: ZJJ administration significantly decreased the level of blood glucose and improved the peripheral insulin resistance in diabetic rats. Besides, ZJJ attenuated the depression-like behavior and the cognitive dysfunction in rats with diabetes. Furthermore, we found the upregulation of protein expression of phospho-IR, phospho-IRS-1, phospho-PI3K, and phospho-AKT in the hippocampus of diabetic rats after being treated with ZJJ. Moreover, the above proteins are increased not only in the neuron but also in the astrocyte after ZJJ administration. In addition, ZJJ increased the content of ATP, glycogen, and lactate, as well as the expression of GLUT4 and MCT4 in the hippocampus of diabetic rats.

Conclusions: These findings suggest that ZJJ improves the depression-like behavior of diabetic rats by activating the IR/IRS-1 signaling pathway in both hippocampal neuron and astrocyte. And the brain IR/IRS-1 signaling pathway plays an important role in astrocyte-neuron metabolic coupling, providing a potential mechanism by which the IR/IRS-1 signaling pathway may contribute to the treatment of ZJJ on diabetes-related depression.
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http://dx.doi.org/10.1155/2021/6688723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195672PMC
June 2021

The Hidden Diversity of Diatrypaceous Fungi in China.

Front Microbiol 2021 31;12:646262. Epub 2021 May 31.

The Key Laboratory for Silviculture and Conservation of Ministry of Education, Beijing Forestry University, Beijing, China.

In this study, we investigated the diversity of diatrypaceous fungi from six regions in China based on morpho-molecular analyses of combined ITS and gene regions. We accept 23 genera in with 18 genera involved in the phylogram, and the other five genera are lacking living materials with sequences data. Eleven species included in four genera (. , , , and ) have been isolated from seven host species, of which nine novel species (. , , , , , , , , and ), a known species of , and a new record of from the host genus are included. Current results show the high diversity of which are wood-inhabiting fungi in China.
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http://dx.doi.org/10.3389/fmicb.2021.646262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200573PMC
May 2021

BP230 IgE autoantibodies in topical-steroid-resistant bullous pemphigoid.

J Dermatol 2021 Jun 14. Epub 2021 Jun 14.

Department of Dermatology, School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: IgE autoantibodies targeting BP230 can be identified in 38%-68% of bullous pemphigoid (BP) patients, yet the diagnostic and pathogenic value of anti-BP230 IgE still remains inconclusive.

Objective: We intend to investigate the clinical and immunological characteristics of anti-BP230 IgE in BP patients.

Methods And Results: Fifty-four BP patients were divided into two groups based on the responsiveness of a topical steroid. We investigated clinical features and IgE autoantibodies profiles by indirect immunofluorescence, ELISA and western blot between the two groups. BP disease area index (BPDAI) scores, total IgE, peripheral eosinophil counts, and anti-BP230 IgE level were significantly higher in the topical-steroid-resistant group. The majority of topical-steroid-resistant patients present with blister/erythematous phenotype (64.3%) and anti-BP230 IgE (59.5%), which correlates with total IgE levels. ELISAs of domain-specific BP230 recombinant proteins indicated that IgE in the topical-steroid-resistant group can react with all seven domains of BP230 and more frequently with the BP230-R1 epitope.

Conclusion: Anti-BP230 IgE is more frequently observed in topical-steroid-therapy-resistant patients and the prefers R1 domain of BP230, which is not included in commercially available testing kits. Our study further suggests the pathogenic role of anti-BP230 IgE in BP. Performing anti-BP230 IgE detection can serve as an indicator for initiating systemic steroid therapy.
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http://dx.doi.org/10.1111/1346-8138.15952DOI Listing
June 2021

Proteomic analyses of plasma-derived exosomes in immunoglobulin (Ig) G4-related disease and their potential roles in B cell differentiation and tissue damage.

J Autoimmun 2021 Aug 6;122:102650. Epub 2021 Jun 6.

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Beijing, China. Electronic address:

Objective: To investigate the proteomic profiles of plasma exosomes isolated from patients with immunoglobulin (Ig) G4-related disease (IgG4-RD) and to determine their potential roles in B cell differentiation and tissue damage.

Methods: One hundred untreated IgG4-RD patients and 135 sex- and age-matched healthy controls (HCs) were enrolled in this study. A combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tandem mass tag (TMT)-label quantitation was used for proteomic profiling. Differentially expressed proteins were validated by Western blot, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) analyses. B cell activation, apoptosis, differentiation and reactive oxygen species (ROS) production were analyzed by flow cytometry. We also analyzed the correlations between differentially expressed complement proteins and laboratory parameters.

Results: A total of 178 differentially expressed proteins were identified in plasma exosomes in IgG4-RD patients compared with HCs, and these proteins were enriched predominantly in the complement cascade pathway. Furthermore, reduced expression levels of complement components C3 and C5 in IgG4-RD were correlated with clinical parameters. Following stimulation with IgG4-RD plasma exosomes, the percentages of naïve B cells decreased, while those of memory B cells and plasmablasts increased; the levels of cytochrome c, somatic (CYCS) and downstream complement system activation also increased. Moreover, ROS production was greater in B cells of IgG4-RD patients than in those of HCs. In affected submandibular glands, the BCR signalling pathway was activated, and exosomes were enriched.

Conclusion: Proteomic profiling revealed that plasma exosome proteins may participate in the pathogenesis of IgG4-RD through complement activation and may be involved in B cell differentiation and activation of the B cell auto-oxidative damage pathway.
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http://dx.doi.org/10.1016/j.jaut.2021.102650DOI Listing
August 2021

Rapid Electrochemical Screening of Phenylketonuria Maker Depending on Dehydrogenase Attached to the Pt-Doped Reduced Graphene Oxide Nanocomposites.

J Biomed Nanotechnol 2021 May;17(5):921-931

The State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Phenylketonuria (PKU) is a common disease associated with amino acid metabolism, and usually occurs in newborns. It can cause serious neurological diseases and even death. However, owing to inadequate-effective treatment, it can only be slowed by a low-phenylalanine (Phe) diet. In addition, PKU screening is essential for newborns in many countries. Therefore, rapid screening is crucial for preventing damage and meeting the large sample diagnosis demand. For confirmed patients, a convenient method to monitor their regular Phe levels is required. However, current clinical methods do not meet the rapid screening and convenient monitoring requirements. Herein, a rapid and facile electrochemical device based on platinum-doped reduced graphene oxide nanocomposites was developed to detect PKU biomarker-Phe. The results demonstrated that the developed electrode has great sensitivity, selectivity, and stability. The detection range was 0.0001 mM to 6 mM with a limit of detection of 0.01 μM. Therefore, this work offers a simple and rapid method for point-of-care PKU screening and daily monitoring.
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http://dx.doi.org/10.1166/jbn.2021.3067DOI Listing
May 2021

Local immune microenvironment of skin may play an important role in the development of pretibial myxedema.

Exp Dermatol 2021 May 28. Epub 2021 May 28.

Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves' disease (GD). Although fibroblast stimulated by thyroid-stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM. Results obtained on PTM patients indicate increased thyroid-stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin-associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.
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http://dx.doi.org/10.1111/exd.14402DOI Listing
May 2021

Association Between the Types of Posterior Staphyloma and Their Risk Factors in Pathological Myopia.

Transl Vis Sci Technol 2021 04;10(4)

Zhengzhou University People's Hospital, Henan Eye Hospital and Henan Eye Institute, Henan Provincial People's Hospital, Zhengzhou, Henan, China.

Purpose: The purpose of this study was to investigate the relationship of posterior staphyloma (PS) types in pathological myopia (PM) with age, best-corrected visual acuity (BCVA), spherical equivalent (SE), axial length (AL), and myopic retinoschisis (MRS) using three-dimensional magnetic resonance imaging (3D-MRI) and optical coherence tomography (OCT).

Methods: This retrospective, cross-sectional study included 108 eyes of 59 patients with PM from the Henan Eye Institute, China. We classified the PS types based on current international classification criteria and analyzed the risk factors (age, AL, MRS, and BCVA).

Results: Most of the patients with bilateral PM had the same PS type (80.43%) in both eyes. Complex PS was more common in elderly patients than in younger patients (P < 0.05). Eyes with wide macular PS had a longer AL (P = 0.012) and worse BCVA (P = 0.049) than those with other PS types. MRS was always comorbid with PS (93.33%), and macular PS was the most common (82.14%).

Conclusions: Complex PS is associated with patient age. PS is related to MRS, and these changes observed by 3D-MRI and OCT affect the prognosis of visual acuity. The 3D-MRI scans shows changes in the eye shape and PS efficiently.

Translational Relevance: In patients with PM, 3D-MRI can guide the planning of posterior scleral reinforcement.
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http://dx.doi.org/10.1167/tvst.10.4.5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039568PMC
April 2021

Chinese guidelines on the clinical application of 5-aminolevulinic acid-based photodynamic therapy in dermatology (2021 edition).

Photodiagnosis Photodyn Ther 2021 May 12;35:102340. Epub 2021 May 12.

Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address:

Photodynamic Therapy with 5-aminolevulinic acid (ALA-PDT) has been widely applied in the treatment of skin diseases in China. To further standardize, guide, and promote the clinical applications of ALA-PDT in dermatology, the Chinese Society of Dermatology, Chinese Association of Rehabilitation Dermatology, Photomedicine Therapeutic Equipment Group of Committee on Skin Disease, and Cosmetic Dermatology of China Association of Medical Equipment invited relevant experts engaged in ALA-PDT to revise and update the first edition of "Clinical application of 5-aminolevulinic acid-based photodynamic therapy: an expert consensus statement" and establish a more current edition, to provide an updated reference for Chinese dermatologists in clinical practice. In the guideline, the expert group reached consensus opinions on ALA-PDT with regard to mechanisms of action, therapeutic protocol, clinical applications, adverse reactions and countermeasures, precautions, care, and evaluation of efficacy.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102340DOI Listing
May 2021

Effects of Amyloid Precursor Protein Overexpression on NF-κB, Rho-GTPase and Pro-Apoptosis Bcl-2 Pathways in Neuronal Cells.

Rep Biochem Mol Biol 2021 Jan;9(4):417-425

Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder that causes cognitive dysfunction. Previous studies have suggested that amyloid plaques, mainly comprising of amyloid-beta peptides, play a pivotal role in AD pathophysiology. This study focuses on the evaluation of the effects of amyloid precursor protein (APP) overexpression on NF-κB, Rho-GTPase and Bcl-2 mediated pro-apoptotic pathways in neuronal cells.

Methods: A lentiviral transduction system was used to generate SH-SY5Y cells overexpressing APP. Immunoblotting was conducted to determine expression levels of NF-κB, Rho-GTPase, and Bcl-2 family proteins in the APP overexpressed cells.

Results: In the NF-κB signaling pathway, APP-overexpressing SH-SY5Y cells showed that there was a reduction of p-NF-κB (p< 0.05) and IKKα. Subsequently, there was upregulation of protein expression of NF-Κb, IKKβ and IκBα. On the other hand, protein expression of RhoC (p< 0.05) and Rac1/2/3 was upregulated as compared to the control group. Meanwhile, a decrease in RhoA, Cdc42 (p< 0.05) and p-Rac1/cdc42 protein levels was observed in the APP-overexpressed group. Lastly, in the pro-apoptotic pathway, the expression of Bcl-2, Bid, Bok and Puma (p< 0.05) was up regulated in the APP-overexpressed group. Downregulation of Bad and Bim expression was observed in the APP-overexpressed as compared to the control group, and Bax expression remained unchanged in the APP-overexpressed group.

Conclusion: APP overexpression regulated signaling in the NF-κB, Rho-GTPase and Bcl-2 family pathways in neuronal cells, suggesting that these are involved in promoting neuronal survival and modulating synaptic plasticity in AD. However, further studies are essential to elucidate the APP-mediated mechanism of action.
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http://dx.doi.org/10.52547/rbmb.9.4.417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068452PMC
January 2021

EpCAM promotes endosomal modulation of the cortical RhoA zone for epithelial organization.

Nat Commun 2021 04 13;12(1):2226. Epub 2021 Apr 13.

Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, Paris, France.

At the basis of cell shape and behavior, the organization of actomyosin and its ability to generate forces are widely studied. However, the precise regulation of this contractile network in space and time is unclear. Here, we study the role of the epithelial-specific protein EpCAM, a contractility modulator, in cell shape and motility. We show that EpCAM is required for stress fiber generation and front-rear polarity acquisition at the single cell level. In fact, EpCAM participates in the remodeling of a transient zone of active RhoA at the cortex of spreading epithelial cells. EpCAM and RhoA route together through the Rab35/EHD1 fast recycling pathway. This endosomal pathway spatially organizes GTP-RhoA to fine tune the activity of actomyosin resulting in polarized cell shape and development of intracellular stiffness and traction forces. Impairment of GTP-RhoA endosomal trafficking either by silencing EpCAM or by expressing Rab35/EHD1 mutants prevents proper myosin-II activity, stress fiber formation and ultimately cell polarization. Collectively, this work shows that the coupling between co-trafficking of EpCAM and RhoA, and actomyosin rearrangement is pivotal for cell spreading, and advances our understanding of how biochemical and mechanical properties promote cell plasticity.
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http://dx.doi.org/10.1038/s41467-021-22482-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044225PMC
April 2021

Diffuse telangiectasia: A clue to the TEMPI syndrome.

JAAD Case Rep 2021 Apr 27;10:99-101. Epub 2021 Feb 27.

Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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http://dx.doi.org/10.1016/j.jdcr.2021.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008156PMC
April 2021

[Effect of Baihe Dihuang Decoction on synaptic plasticity of hippocampus in rats with anxious depression].

Zhongguo Zhong Yao Za Zhi 2021 Mar;46(5):1205-1210

Science and Technology Innovation Center/State Key Laboratory Breeding Base of Chinese Medicine Powder and Innovative Medicine,Hunan University of Chinese Medicine Changsha 410208,China.

To explore the effect of Baihe Dihuang Decoction on the synaptic plasticity of hippocampal neurons in rats with anxious depression. Fifty SD rats were randomly divided into normal group, model group, venlafaxine group(6.75 mg·kg~(-1)), high-dose Baihe Dihuang Decoction group(8.64 g·kg~(-1)) and low-dose Baihe Dihuang Decoction group(4.32 g·kg~(-1)). Chronic restraint stress(6 h) combined with corticosterone(ih, 30 mg·kg~(-1)) was used to establish an anxious depression model, and 7 days after modeling, the administration started and continued for 21 days. The anxiety and depression-like behaviors of the rats were evaluated. Golgi-Cox staining and electron microscopy were used to observe the morphology and ultrastructural changes of synaptic dendrites. Immunofluorescence was used to detect the expression of hippocampal synaptic plasticity protein synapsin-1 and postsynaptic density protein 95(PSD-95). Western blot method was used to detect the expression of functional protein synaptophysin(SYP) and synaptic Ras GTPase activating protein(SynGap). The results showed that the rats in the model group had obvious anxiety and depression-like behaviors, the hip-pocampal dendritic spine density and branch length were reduced, the number of synapses was cut, and the internal structure was da-maged. The average fluorescence intensity of synapsin-1 and PSD-95 was significantly reduced and the expression of SYP and SynGap also decreased. High-dose Baihe Dihuang Decoction could significantly improve the anxiety and depression-like behaviors of model rats, relieve synaptic damage, and increase the expression of synapsin-1, PSD-95, SYP, and SynGap proteins. Therefore, we believe that Baihe Dihuang Decoction can improve anxiety and depression behaviors by regulating the synaptic plasticity of hippocampal neurons.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201221.401DOI Listing
March 2021

Cyclophosphamide loaded thermo-responsive hydrogel system synergize with a hydrogel cancer vaccine to amplify cancer immunotherapy in a prime-boost manner.

Bioact Mater 2021 Oct 9;6(10):3036-3048. Epub 2021 Mar 9.

State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, PR China.

Although neoantigen-based cancer vaccines show great potential in cancer immunotherapy due to their ability to induce effective and long-lasting anti-tumor immunity, their development is hindered by the limitations of neoantigens identification, low immunogenicity, and weak immune response. Cyclophosphamide (CTX) not only directly kills tumors but also causes immunogenic cell death, providing a promising source of antigens for cancer vaccines. Herein, a combined immunotherapy strategy based on temperature-sensitive PLEL hydrogel is designed. First, CTX-loaded hydrogel is injected intratumorally into CT26 bearing mice to prime anti-tumor immunity, and then 3 days later, PLEL hydrogels loaded with CpG and tumor lysates are subcutaneously injected into both groins to further promote anti-tumor immune responses. The results confirm that this combined strategy reduces the toxicity of CTX, and produces the cytotoxic T lymphocyte response to effectively inhibit tumor growth, prolong survival, and significantly improve the tumor cure rate. Moreover, a long-lasting immune memory response is observed in the mice. About 90% of the cured mice survive for at least 60 days after being re-inoculated with tumors, and the distant tumor growth is also well inhibited. Hence, this PLEL-based combination therapy may provide a promising reference for the clinical promotion of chemotherapy combined with cancer vaccines.
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http://dx.doi.org/10.1016/j.bioactmat.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960683PMC
October 2021

Distribution of anti-melanoma differentiation associated gene 5 (MDA5) IgG subclasses in MDA5+ dermatomyositis.

Rheumatology (Oxford) 2021 Mar 20. Epub 2021 Mar 20.

Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 200025 Shanghai, China.

Objectives: The anti-melanoma differentiation-associated gene 5 (MDA5) antibody is the main predictor of interstitial lung disease (ILD) in dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM). Nevertheless, a subset of MDA5+ patients have a favorable prognosis. We aimed to determine the possibility of using anti-MDA5 antibody isotypes and IgG subclasses for evaluating ILD risk.

Methods: The isotypes (IgG, IgA and IgM) of anti-MDA5 were detected in serum samples of 36 anti-MDA5+ patients with DM/CADM using enzyme-linked immunosorbent assay (ELISA). IgG subclasses of anti-MDA5 antibodies were further investigated. Laboratory findings and cumulative survival were analyzed based on the isotypes of anti-MDA5 and subclasses of anti-MDA5 IgG.

Results: Among the MDA5+ patients with DM/CADM, the positive rates of anti-MDA5 IgG, IgA, IgM were 100%, 97%, and 6%, respectively. The positive rates of anti-MDA5 IgG1, IgG2, IgG3, and IgG4 were 72%, 25%, 0%, and 28%, respectively. The incidence of acute interstitial pneumonia, mortality rate, and serum ferritin were significantly higher in anti-MDA5 IgG1+ patients than those in anti-MDA5 IgG1- patients with DM/CADM (P = 0.0027, 0.015, 0.0011, respectively). The sensitivity and specificity of anti-MDA5 IgG1 for predicting mortality were 100% and 41.7%, respectively. A combination of anti-MDA5 IgG1 and IgG4 for predicting mortality, yielded better specificity (87.5%).

Conclusion: IgA and IgG are the primary anti-MDA5 antibody isotypes. Anti-MDA5 IgG1 is the primary component of MDA5 IgG subclasses and anti-MDA5 IgG1 and IgG4 might serve as useful biomarkers for predicting mortality in DM-ILD.
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http://dx.doi.org/10.1093/rheumatology/keab268DOI Listing
March 2021

The Pathogenic Role of CD4 Tissue-Resident Memory T Cells Bearing T Follicular Helper-Like Phenotype in Pemphigus Lesions.

J Invest Dermatol 2021 Mar 16. Epub 2021 Mar 16.

Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

In skin lesions caused by pemphigus, a group of life-threatening autoimmune bullous diseases, an over-representation of CD4 tissue-resident memory T (T) cells was found. We sought to investigate the contributions of CD4 T cells to the severity and refractoriness of pemphigus and their role in local immunological pathogenesis. Our data showed that CD4 T cells accumulated significantly in pemphigus skin lesions. These CD4 T cells expressed a specific set of T follicular helper cell‒related costimulatory molecules. We also found that CD4 T cells remaining in the lesions produced IL-17A and IL-21. In vitro, CD4 T cells exhibited strong support and assistance to autoantibody production. Through transcriptomic sequencing and bioinformatics analysis, we identified that the transcription factor IRF4 was responsible for IL-21 overexpression and autoantibody production. Our results showed that T follicular helper-like CD4 T cells in pemphigus lesions promoted local autoantibody production, resulting in the formation and recurrence of lesions, which supports targeting this cell subset in pemphigus treatment. IRF4 might serve as a potential therapeutic target.
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http://dx.doi.org/10.1016/j.jid.2021.01.030DOI Listing
March 2021

Enhancing Osseointegration of TC4 Alloy by Surficial Activation Through Biomineralization Method.

Front Bioeng Biotechnol 2021 23;9:639835. Epub 2021 Feb 23.

Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiao Tong University, Shanghai, China.

Titanium (Ti) alloys have been applied to biomedical implants for a long time. Although Ti alloys are biocompatible, efforts have been continuously made to improve their bone conductivity and osteogenesis for enhancing their performance. Silk fibroin (SF) is a natural biomaterial with excellent biomedical and mechanical properties, and hydroxyapatite (HAP) nanocomposites derived from SF are promising for producing "artificial bone" owing to their biomedical applicability and strong mechanical functions. Therefore, we built an SF coating on the surface of Ti-6Al-4V alloy, and then the incubated SF-coated Ti alloy were immersed in simulated body fluid to induce mineral deposition of HAP on the alloys. The results from Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) analysis, and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) confirmed the deposition of a mineral layer on the SF film surface. The proliferation, adhesion, and differentiation of MG-63 were tested, along with the BMP-2, COX-2, and OPG expression and protein content in the MG-63. Both Ti + SF and Ti + SF + HAP groups exhibited significantly better performance than a control Ti group with regard to the cell adhesion, cell proliferation, and protein expression. Furthermore, the hybrid layer comprising HAP and SF delivered more significant improvement of the osseointegration than the SF alone. It is hoped that the proposed methods can be used for constructing modified surfaces on Ti alloys, as they endowed the implants with good osteogenic potential.
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http://dx.doi.org/10.3389/fbioe.2021.639835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940542PMC
February 2021

Assessment of Isolates From Conifer Cankers in China, With the Descriptions of Four New Species.

Front Plant Sci 2021 18;12:636460. Epub 2021 Feb 18.

The Key Laboratory for Silviculture and Conservation of Ministry of Education, Beijing Forestry University, Beijing, China.

species are widely distributed and often occur as endophytes, saprobes or phytopathogens. They primarily cause canker and dieback diseases of woody host plants, leading to the growth weakness or death of host plants, thereby causing significant economic and ecological losses. In order to reveal the diversity of species associated with canker and dieback diseases of coniferous trees in China, we assessed 11 spp. represented by 28 fungal strains from symptomatic branches or twigs of coniferous trees, i.e., in China. Through morphological observations and multilocus phylogeny of ITS, LSU, α, and gene sequences, we focused on four novel species (, and ) associated with . This study represented the first attempt to clarify the taxonomy of species associated with canker and dieback symptoms of coniferous trees in China.
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http://dx.doi.org/10.3389/fpls.2021.636460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930227PMC
February 2021

[Predictive value of MB isoenzyme of creatine kinase and poisoning severity score in the prognosis of patients with wasp sting].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jan;33(1):105-108

Department of Emergency, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, Henan, China.

Objective: To explore the predictive value of MB isoenzyme of creatine kinase (CK-MB) and poisoning severity score (PSS) in the clinical prognosis of patients with wasp sting.

Methods: A retrospective study was conducted. The clinical data of patients who were stung by wasps admitted to emergency department of the First Affiliated Hospital of Henan University of Science and Technology from July 2017 to November 2019 were collected. The 24-hour acute physiology and chronic health evaluation II (APACHE II), CK-MB and PSS scores of the patients were collected after admission, and 28-day outcome was recorded. Spearman correlation analysis method was used to analyze the correlation between CK-MB and PSS score. Logistic regression model was used to construct joint predictors, and the receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of various indicators for 28-day prognosis of patients with wasp stings.

Results: Finally 90 patients were included in the analysis. There were 67 patients survived at 28 days, and 23 dead with the 28-day mortality of 25.6%. APACHE II score, CK-MB and PSS score in the death group were significantly higher than those in the survival group [APACHE II score: 19.7±2.7 vs. 13.7±2.3, CK-MB (U/L): 183 (151, 243) vs. 36 (21, 75), PSS score: 17.7±2.6 vs. 9.3±4.5, all P < 0.01]. The correlation analysis showed that CK-MB and PSS score were positively correlated (r = 0.843, P < 0.01). Logistic regression model fitted CK-MB and PSS score, and Hosmer-Lemeshow test showed that the model fitted well. ROC curve analysis showed that the area under ROC curve (AUC) of CK-MB for predicting 28-day outcome was 0.957, the sensitivity was 91.3%, and the specificity was 88.1%; the AUC of PSS score was 0.908, the sensitivity was 91.3%, and the specificity was 90.8%. The AUC of CK-MB combined with PSS score was 0.964, the sensitivity was 100%, and the specificity was 79.4%, indicating that CK-MB combined with PSS score had higher predictive value and higher sensitivity for 28-day prognosis of patients with wasp sting.

Conclusions: High CK-MB level and high PSS score in early stage of wasp sting injury indicate poor prognosis. Both CK-MB and PSS score can be used as predictors for predicting the prognosis of patients with wasp stings. In addition, CK-MB combined with PSS score have greater predictive value.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200810-00571DOI Listing
January 2021

Recent progress in nanoformulations of cabazitaxel.

Biomed Mater 2021 Feb 5. Epub 2021 Feb 5.

West China Hospital West China Medical School, Sichuan University, Sichuan University, Chengdu, 610041, CHINA.

The antitumor efficacy of various paclitaxel (PTX) and docetaxel (DTX) formulations in clinical applications is seriously affected by drug resistance. Cabazitaxel, a second-generation taxane, exhibits greater anticancer activity than paclitaxel and docetaxel and has low affinity for the P-glycoprotein (P-gp) efflux pump because of its structure. Therefore, cabazitaxel has the potential to overcome taxane resistance. However, owing to the high systemic toxicity and hydrophobicity of cabazitaxel and the instability of its commercial preparation, Jevtana®, the clinical use of cabazitaxel is restricted to patients with metastatic castration-resistant prostate cancer (mCRPC) who show progression after docetaxel-based chemotherapy. Nanomedicine is expected to overcome the limitations associated with cabazitaxel application and surmount taxane resistance. This review outlines the drug delivery systems of cabazitaxel published in recent years, summarizes the challenges faced in the development of cabazitaxel nanoformulations, and proposes strategies to overcome these challenges.
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http://dx.doi.org/10.1088/1748-605X/abe396DOI Listing
February 2021

An uncoordinated tertiary nitrogen based tricarboxylate calcium network with Lewis acid-base dual catalytic sites for cyanosilylation of aldehydes.

Dalton Trans 2021 Feb;50(5):1740-1745

Key Laboratory of Magnetic Molecules and Magnetic Information Materials (Ministry of Education), Institute of Chemistry and Culture, School of Chemistry and Material Science, Shanxi Normal University, Linfen 041004, China.

The design and utilization of dual sites for synergistic catalysts has been recognised as an efficient method towards high-efficiency catalysis in the cyanosilylation of aldehydes, which gives key intermediates for the synthesis of a number of valuable natural and pharmaceutical compounds. However, most of the reported dual-site catalysts for this reaction were homogeneous, accompanied by potential deactivation through internal complexation of the dual sites. Herein, by the rational selection of an uncoordinated tertiary nitrogen based tricarboxylic ligand (tris[(4-carboxyl)-phenylduryl]amine, H3TCBPA), a new three-dimensional calcium-based metal-organic framework (MOF), Ca3(TCBPA)2(DMA)2(H2O)2 (1, where TCBPA = ionized tris[(4-carboxyl)-phenylduryl]amine and DMA = N,N-dimethylacetamide), possessing accessible dual catalytic sites, Lewis-basic N and Lewis-acidic Ca, has been designed and constructed by a one-pot solvothermal reaction. As expected, 1 is capable of dually and heterogeneously catalysing the cyanosilylation of aldehydes at room temperature, and can be reused for at least 6 runs with a maximum turnover number (TON) of 1301, which is superior to most reported cases. Additionally, 1 shows CO2 adsorption ability and conversion with epoxides, which is beneficial for the establishment of a sustainable society.
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http://dx.doi.org/10.1039/d0dt03747hDOI Listing
February 2021

Resatorvid Relieves Breast Cancer Complicated with Depression by Inactivating Hippocampal Microglia Through TLR4/NF-κB/NLRP3 Signaling Pathway.

Cancer Manag Res 2020 18;12:13003-13014. Epub 2020 Dec 18.

Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People's Republic of China.

Background: Breast cancer is one of the most common cancer with high risk in females all over the world. It is usually complicated with depression, which can further accelerate the development and progression of breast tumors. We aim to identify a new drug and identify its functional mechanism in the regulation of hippocampal microglia (MG) in breast cancer complicated with depression (BCCD).

Methods: The activation model of MG was established by treatments from corticosterone (CORT) or lipopolysaccharides (LPS). The inhibitory effects of resatorvid on MG were investigated by CCK-8, ROS, immunofluorescence, TUNEL, scratch test, ELISA, RT-qPCR and Western blot. BCCD animal model was established using 4T1 inflammatory breast cancer cells and CORT treatment in vitro. Open field experiment (OFE), tail suspension test (TST), ELISA, RT-qPCR and Western blot experiments were utilized to examine the effects of resatorvid on the animal model in vivo.

Results: The cell viability and migration ability of the BCCD model group were suppressed. The expressions of inflammatory factors, ROS, and the apoptotic rate of the BCCD model group were up-regulated, in contrast to the control group. The expressions related to the TLR4/NF-κB/NLRP3 signaling in the BCCD model group were also elevated. Resatorvid reversed the above changes, which showed good therapeutic effects in depression-related behavioral changes, tumor treatment, and blood-brain barrier function.

Conclusion: In summary, resatorvid inhibited the activation of hippocampal MG in BCCD by regulating TLR4/NF-κB/NLRP3 signaling pathway.
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http://dx.doi.org/10.2147/CMAR.S279800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755376PMC
December 2020

IL-21 enhances STAT3/Blimp-1 signaling pathway in B cells and contributes to plasma cell differentiation in newly diagnosed patients with myasthenia gravis.

Immunol Res 2021 02 3;69(1):59-70. Epub 2020 Nov 3.

Department of Neurology, Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai West Road, Quanshan District, Xuzhou, Jiangsu, China.

The transcription factor Blimp-1 is necessary for the B cell differentiation toward immunoglobulin-secreting plasma cells. However, the immunopathological mechanisms of Blimp-1 that regulates B cell differentiation remain unclear in MG. The purpose of this study was to perform a quantitative and functional analysis of Blimp-1 in MG. A total of 34 patients with MG (18 ocular MG (OMG) and 16 generalized MG (GMG) and 20 healthy controls (HC) were recruited in this study. CD19 B cells were isolated by positive selection using CD19 beads. The expression of Blimp-1 and p-STAT3 protein in isolated B cells was assessed by Western blot. Plasma cells were analyzed by flow cytometry. Serum IL-21 levels were detected by ELISA. Our data demonstrated that Blimp-1 in peripheral blood B cell of MG patients was significantly increased compared with HC. The increased expression of Blimp-1 was positively associated with clinical severity score (QMGs), plasma cell frequency, and serum IL-21 levels. Furthermore, glucocorticoid (GC) treatment reduced the expression of Blimp-1 and p-STAT3 in B cells, and this change was accompanied with relieved clinical severity, reduced plasma cell frequency, and decreased serum IL-21 levels. In vitro assay demonstrated that IL-21 stimulation upregulated STAT3 phosphorylation, increased Blimp-1 expression in B cells, and promoted plasma cell differentiation, and these processes could be inhibited by dexamethasone or STAT3 inhibitor stattic. This work indicates for the first time that aberrant expression of Blimp-1 exists on B cells and contributes to the plasma cell differentiation in MG patients. Modulation of IL-21/STAT3/Blimp-1 signaling pathway in B cells may be one of the mechanisms of glucocorticoid in the treatment of MG.
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http://dx.doi.org/10.1007/s12026-020-09164-2DOI Listing
February 2021

AgS nanoparticle-mediated multiple ablations reinvigorates the immune response for enhanced cancer photo-immunotherapy.

Biomaterials 2021 01 13;264:120451. Epub 2020 Oct 13.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China. Electronic address:

Photothermal therapy (PTT) has been widely used in cancer treatment in recent years. However, it is difficult to completely eliminate tumors by single PTT, and the effects of single dose of PTT frequency on the therapeutic outcome of PTT and the multiple PTT-induced immune response in cancer therapy also remain unclear. Here, water-soluble AgS nanoparticles (NPs) with optimal particle size (~15 nm) were synthesized and used as the PTT agents. The in vitro and in vivo results demonstrated that AgS NPs had good photothermal conversion in response to the irradiation of an 808 nm laser, and the results indicated that the NPs have potential as contrast agents for photoacoustic imaging as well as good biocompatibility. The in vivo results further revealed that the frequency of the AgS NP-mediated PTT affected the cancer therapeutic outcome. The increase of frequency efficiently reduced the primary tumor recurrence and alleviated metastasis. The present study suggested that the mechanism involves multiple PTT cycles inhibiting the proliferation of primary tumor cells and stimulating the systematic immune response in the mouse breast cancer model. Therefore, frequency optimization in photothermal ablation may provide a promising strategy to enhance the therapeutic outcome in cancer therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120451DOI Listing
January 2021

Abnormal Glu/mGluR/PI3K pathway in the hippocampal neurovascular unit leads to diabetes-related depression.

Neural Regen Res 2021 Apr;16(4):727-733

Institute of Innovation and Applied Research; Key Laboratory of Chinese Material Medical Power and Innovation Drugs Established by Human Provincial Government and Ministry, Hunan University of Chinese Medicine; The Domestic First Class Construction Discipline of Chinese Medicine in Hunan University of Chinese Medicine, Changsha, Hunan Province, China.

Our previous studies have shown that glutamate and hippocampal neuron apoptosis are key signals and direct factors associated with diabetes-related depression, and structural and functional damage to the hippocampal neurovascular unit has been associated with diabetes-related depression. However, the underlying mechanism remains unclear. We hypothesized that diabetes-related depression might be associated with the glutamate (Glu)/metabotropic glutamate receptor2/3 (mGluR)/phosphoinositide 3-kinase (PI3K) pathway, activated by glucocorticoid receptors in the hippocampal neurovascular unit. To test this hypothesis, rat hippocampal neurovascular unit models, containing hippocampal neurons, astrocytes, and brain microvascular endothelial cells, were treated with 150 mM glucose and 200 µM corticosterone, to induce diabetes-related depression. Our results showed that under conditions of diabetes complicated by depression, hippocampal neurovascular units were damaged, leading to decreased barrier function; elevated Glu levels; upregulated glucocorticoid receptor, vesicular glutamate transporter 3 (VGLUT-3), and metabotropic glutamate receptor 2/3 (mGluR) expression; downregulated excitatory amino acid transporter 1 (EAAT-1) expression; and alteration of the balance of key proteins associated with the extracellular signal-regulated kinase (ERK)/glial cell-derived neurotrophic factor (GDNF)/PI3K signaling pathway. Moreover, the viability of neurons was dramatically reduced in the model of diabetes-related depression, and neuronal apoptosis, and caspase-3 and caspase-9 expression levels, were increased. Our results suggest that the Glu/mGluR/PI3K pathway, induced by glucocorticoid receptor activation in the hippocampal neurovascular unit, may be associated with diabetes-related depression. This study was approved by the Laboratory Animal Ethics Committee of The First Hospital of Hunan University of Chinese Medicine, China (approval No. HN-ZYFY-2019-11-12) on November 12, 2019.
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http://dx.doi.org/10.4103/1673-5374.296418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067948PMC
April 2021

The surface dominant antigen MUC1 is required for colorectal cancer stem cell vaccine to exert anti-tumor efficacy.

Biomed Pharmacother 2020 Dec 2;132:110804. Epub 2020 Oct 2.

Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Nanjing 210009, China. Electronic address:

Colorectal cancer (CRC), initiated and maintained by colorectal cancer stem cells (CCSCs), ranks the third most common cancers and has drawn wide attentions worldwide. Therefore, targeting clearance of CCSCs has become an important strategy of CRC immunotherapy. Mucin1 (MUC1) is a tumor-associated cell surface antigen of CRC, but its role in CCSC vaccine remains unclear. In the study, we demonstrated that MUC1 may be a dominant antigen to exert antitumor immunity in CCSC vaccine. First, CCSCs were enriched from CT26 cell line via a serum-free sphere formation approach, and were identified by detecting expression of CD133, ALDH, and ALCAM. Then, the isolated CCSCs were frozen for 30 min and thawed for 30 min to prepare the cell lysate. The specific anti-MUC1 antibody was added to the cell lysate to neutralize the dominant antigen MUC1. Finally, mice were subcutaneously immunized with the cell lysate, followed by a challenge with CT26 cells at one week after final vaccination. Attractively, CCSC vaccine significantly activated the NK cells, T cells, and B cells, resulting in inhibiting the tumor growth via a target killing of CCSCs as evidenced by a decrease of CD133cells in tumor compared to CCSC vaccine with specific anti-MUC1 antibody. In addition, CCSC vaccine reduced expression of inflammatory factors in vaccinated mice. As expected, neutralizing antibody against MUC1 significantly impaired the antitumor efficacy of CCSC vaccine. Overall, CCSC vaccine could serve as a potent vaccine for CRC immunotherapy. The surface dominant antigen MUC1 may play a key role in regulating immunogenicity of CCSCs.
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http://dx.doi.org/10.1016/j.biopha.2020.110804DOI Listing
December 2020

Thalidomide as a potential adjuvant treatment for paraneoplastic pemphigus: A single-center experience.

Dermatol Ther 2020 11 8;33(6):e14353. Epub 2020 Oct 8.

Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Paraneoplastic pemphigus (PNP) is a rare autoimmune bullous disease associated with an underlying malignancy. The survival rate at 5 years is reported to be as low as 38%. Thalidomide is a medication with strong anti-inflammatory, immunomodulatory, antiangiogenic, and sedative properties. Recently, the successful application of thalidomide in several dermatological and hematological disorders inspired us to investigate its potential as an adjuvant treatment for PNP. Here, we report our experience of trial thalidomide therapy in 14 PNP patients. After treatment of their associated tumors, the patients were administered thalidomide (75-100 mg/d) combined with or without low- to mid-dose oral prednisone. Twelve patients completed the therapy. Seven patients (58%) achieved complete remission with no relapse, including two patients who received thalidomide monotherapy. Five patients (42%) died within 1 to 3 months. The 1-year and 2-year survival rates in our case series were 58% and 55%, respectively. The regimen was well tolerated. Although the treatment experience presented has a limited sample size and no control, our results imply that thalidomide may be an effective, safe, and economical treatment option for PNP patients. Further research is needed to better understand the mechanisms of action of thalidomide in PNP.
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http://dx.doi.org/10.1111/dth.14353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816226PMC
November 2020

Structural characteristics and rheological properties of alkali-extracted arabinoxylan from dehulled barley kernel.

Carbohydr Polym 2020 Dec 25;249:116813. Epub 2020 Jul 25.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, Nanchang, Jiangxi Province, 330047, China.

Arabinoxylan (BIF-60) was isolated from barley water-insoluble fiber (BIF) by ethanol precipitation at 60 % (v/v). BIF-60 was composed of xylose (48.5 %) and arabinose (30.3 %). Its average molecular weight was 1360 kDa. Methylation and 1D/2D NMR analysis showed that BIF-60 possessed β-(l→4)-xylan as backbone, comprised of un-substituted (1,4-linked β-Xylp, 56.9 %), mono-substituted (1,2,4-linked and 1,3,4-linked β-Xylp, 22.1 %) and di-substituted (1,2,3,4-lin4ked β-Xylp, 18.4 %) xylose units, as well as other residues (T-Araf-(1→, T-Xylp-(1→, →5)-Araf-(1→, →2)-Araf-(1→, →3)-Araf-(1→ and →4)-Glcp-(1→). BIF-60 exhibited shear-thinning behaviour, low gel stability and weak gelling ability at high concentrations. This work provides a theoretical and experimental basis for molecular structure and properties of the alkali-extracted arabinoxylan from barley kernel, which could guide further functional research and application of barley-derived arabinoxylan.
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http://dx.doi.org/10.1016/j.carbpol.2020.116813DOI Listing
December 2020

BNIP-2 retards breast cancer cell migration by coupling microtubule-mediated GEF-H1 and RhoA activation.

Sci Adv 2020 Jul 31;6(31):eaaz1534. Epub 2020 Jul 31.

Mechanobiology Institute, 5A Engineering Drive 1, National University of Singapore, Singapore 117411, Singapore.

Microtubules display dynamic turnover during cell migration, leading to cell contractility and focal adhesion maturation regulated by Rho guanosine triphosphatase activity. This interplay between microtubules and actomyosin is mediated by guanine nucleotide exchange factor (GEF)-H1 released after microtubule depolymerization or microtubule disconnection from focal adhesions. However, how GEF-H1 activates Rho upon microtubule disassembly remains elusive. Here, we found that BNIP-2, a BCH domain-containing protein that binds both RhoA and GEF-H1 and traffics with kinesin-1 on microtubules, is important for GEF-H1-driven RhoA activation upon microtubule disassembly. Depletion of BNIP-2 in MDA-MB-231 breast cancer cells decreases RhoA activity and promotes cell migration. Upon nocodazole-induced microtubule disassembly, the interaction between BNIP-2 and GEF-H1 increases, while knockdown of BNIP-2 reduces RhoA activation and cell rounding via uncoupling RhoA-GEF-H1 interaction. Together, these findings revealed that BNIP-2 couples microtubules and focal adhesions via scaffolding GEF-H1 and RhoA, fine-tuning RhoA activity and cell migration.
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http://dx.doi.org/10.1126/sciadv.aaz1534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399486PMC
July 2020

Pregnancy exposure to carbon black nanoparticles induced neurobehavioral deficits that are associated with altered mA modification in offspring.

Neurotoxicology 2020 12 9;81:40-50. Epub 2020 Aug 9.

Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, PR China; Dongsheng Lung-Brain Diseases Joint Lab, Chongqing Medical University, Chongqing, 400016, PR China. Electronic address:

Increasing occupational and accidental exposure to carbon black nanoparticles (CBNPs) raise concerns over their possible effects on the nervous system. However, the influences of CBNPs on the neurodevelopment remain unclear. Thus, in this study, pregnant mice were exposed to different doses of CBNPs by intranasal instillation on gestation days 9-18. Our results demonstrated that maternal exposure to CBNPs caused significant changes on maternal behaviors. Pregnancy exposure to CBNPs also delayed the onset of incisor eruption, testes descent and vaginal opening in offspring, and caused the reduced body weight until adulthood. In the neurobehavioral tests, CBNPs-exposed offspring exhibited the elevated latency of negative geotaxis and surface right reflex, reduced grasping time and increased cliff avoidance. Histopathological changes were present in F1 generation but not in F2 generation. Intriguingly, our data revealed that the levels of total mA modification were significantly decreased by CBNPs. Similar trends were observed on the mRNA expressions of mA methyltransferases and demethylases. In summary, these findings provide the novel evidence that pregnancy exposure to CBNPs affects the maternal behaviors and partially induces the neurobehavioral, muscular and histopathological changes in offspring. Of note, these adverse effects may be associated with reduced levels of total mA modification in brain.
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http://dx.doi.org/10.1016/j.neuro.2020.07.004DOI Listing
December 2020
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