Publications by authors named "Xiaoqian Yang"

57 Publications

Triptolide analog LLDT-8 ameliorates psoriasis-like dermatitis in BALB/c mice via suppressing the IL-36α signaling pathway.

Pharmacol Res 2021 May 17;169:105678. Epub 2021 May 17.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address:

Triptolide has shown a good immunosuppressive effect on autoimmune diseases. However, the toxicity limited its widely clinical practice. In this study, we investigated the effects and underlying mechanisms of (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, on a murine psoriasis-like dermatitis model and related cell lines. Here, we showed that LLDT-8 significantly attenuated symptoms of psoriasis-like dermatitis induced by imiquimod (IMQ, a TLR7 agonist) by reducing the psoriasis area and severity index (PASI) score and inflammatory parameters. The action of LLDT-8 was involved in down-regulated interleukin (IL)-36α expression and blocked IL-36α pathway by LC-MS-based label-free quantitative (LFQ) proteomic approach and further experiments. Meanwhile, we observed that LLDT-8 significantly inhibited the expression of IL-36α in R837-treated bone marrow-derived dendritic cells (BMDCs). In conclusion, LLDT-8 notably alleviated IMQ-induced psoriasis-like skin inflammation via suppressing the IL-36α signaling pathway, suggesting LLDT-8 might be a potential drug for the treatment of psoriasis.
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http://dx.doi.org/10.1016/j.phrs.2021.105678DOI Listing
May 2021

Development of the prediction model for hypertension in patients with idiopathic inflammatory myopathies.

J Clin Hypertens (Greenwich) 2021 May 11. Epub 2021 May 11.

Department of Cardiology, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Sichuan, China.

Cardiac involvement is an important cause of morbidity and mortality in patients with idiopathic inflammatory myopathies (IIMs). Hypertension, an important cardiovascular risk factor for the general population, has a crucial role in heart involvement. However, few studies have focused on the hypertension associated with IIMs. This study aimed to develop and assess the prediction model for incident hypertension in patients with IIMs. A retrospective cohort study was performed on 362 patients with IIMs, of whom 54 (14.9%) were given a diagnosis of new-onset hypertension from January 2008 to December 2018. The predictors of hypertension in IIMs were selected by least absolute shrinkage and selection operator (LASSO) regression, multivariable logistic regression, and clinically relevance, and then these predictors were used to draw the nomogram. Discrimination, calibration and clinical usefulness of the model were evaluated using the C-index, calibration plot, and decision curve analysis, respectively. The predicting model was validated by the bootstrapping validation. The nomogram mainly included predictors such as age, diabetes mellitus, triglyceride, low-density lipoprotein-cholesterol (LDL-C), antinuclear antibodies (ANA), and smoking. This prediction model demonstrated good discrimination with a C-index of 0.754 (95%CI, 0.684 to 0.824) and good calibration. The C-index of internal validation was 0.728, and decision curve analysis demonstrated that this nomogram was clinically useful. Clinicians can use this prediction model to assess the risk of hypertension in IIMs patients, and early preventive measures should be taken to reduce the incidence of hypertension in high-risk patients.
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http://dx.doi.org/10.1111/jch.14267DOI Listing
May 2021

Identification and validation of miRNA reference genes in poplar under pathogen stress.

Mol Biol Rep 2021 Apr 4;48(4):3357-3366. Epub 2021 May 4.

Beijing Advanced Innovation Center for Tree Breeding By Molecular Design, College of Biological Sciences and Biotechnology, National Engineering Laboratory for Tree Breeding, Beijing Forestry University, Beijing, 100083, China.

Quantitative real time polymerase chain reaction (qRT-PCR) is a common method to analyze gene expression. Due to differences in RNA quantity, quality, and reverse transcription efficiency between qRT-PCR samples, reference genes are used as internal standards to normalize gene expression. However, few universal genes, especially miRNAs, have been identified as reference so far. Therefore, it is essential to identify reference genes that can be used across various experimental conditions, stress treatments, or tissues. In this study, 14 microRNAs (miRNAs) and 5.8S rRNA were assessed for expression stability in poplar trees infected with canker pathogen. Using geNorm, NormFinder and Bestkeeper reference gene analysis programs, we found that miR156g and miR156a exhibited stable expression throughout the infection process. miR156g, miR156a and 5.8S rRNA were then tested as internal standards to measure the expression of miR1447 and miR171c, and the results were compared to small RNA sequencing (RNA-seq) data. We found that when miR156a and 5.8S rRNA were used as the reference gene, the expression of miR1447 and miR171c were consistent with the small RNA-seq expression profiles. Therefore, miR156a was the most stable miRNAs examined in this study, and could be used as a reference gene in poplar under canker pathogen stress, which should enable comprehensive comparisons of miRNAs expression and avoid the bias caused by different length between detected miRNAs and traditional reference genes. The present study has expanded the miRNA reference genes available for gene expression studies in trees under biotic stress.
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http://dx.doi.org/10.1007/s11033-021-06369-yDOI Listing
April 2021

Blockade of TLRs-triggered macrophage activation by caffeic acid exerted protective effects on experimental ulcerative colitis.

Cell Immunol 2021 Jul 22;365:104364. Epub 2021 Apr 22.

Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Ulcerative colitis (UC) represents a relapsing and inflammatory bowel disease which is commonly linked with the communications between dysfunction of epithelium and mucosal immune responses. Though caffeic acid (CA) has numerous pharmacological capacities, whether CA demonstrates immunoregulation on the mucosal immune responses remains ill-defined. Herein, the present research demonstrated that CA could dramatically attenuate the mucosal inflammation, as evidenced by improving the disease severity, serum biochemical indexes, mucosal ulcerations, loss of epithelium and crypts, and secretion of inflammatory cytokines in the colonic homogenates and explants culture. Consistently, CA could interfere with the infiltration and function of mononuclear macrophages in the mucosa, MLNs, and spleens of UC. Furthermore, CA exerted direct suppressive effects on the activation of BMDMs upon the exposure of TLRs agonists in vitro. Taken together, CA could attenuate DSS-induced murine UC through interfering with the activation of macrophages, which might provide an alternative therapeutic option for UC.
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http://dx.doi.org/10.1016/j.cellimm.2021.104364DOI Listing
July 2021

Purification, characterization and anti-atherosclerotic effects of the polysaccharides from the fruiting body of Cordyceps militaris.

Int J Biol Macromol 2021 Jun 18;181:890-904. Epub 2021 Apr 18.

Institute of Lipid metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China. Electronic address:

Hyperlipidemia is one major cause of atherosclerosis, which is a basic pathological change of cardiovascular diseases. Polysaccharide is a water-soluble component with lipid-lowering effects. In this study, alkaline-extracted polysaccharides were obtained from the fruiting body of C. militaris. Polysaccharides were purified via anion exchange and size exclusion chromatography. Their structural characteristics were investigated via chemical and spectroscopic methods. CM3I was mainly composed of →4)α-D-Glcp(1 → glycosyls and differed from starch due to the presence of →4,6)β-D-Glcp(1 → glycosyls. CM3II was characterized by its backbone, which was composed of →4)-β-D-Manp(1 → 6)-α-D-Manp(1 → 6)-β-D-Manp(1 → linked glycosyls, and especially the presence of O-methyl. Moreover, CM3II exhibited powerful anti-atherosclerotic effects via lowering plasma lipid levels in apolipoprotein E-deficient mice. The underlying mechanisms were attributed to its promoting effect on LXRα and inhibitory effect on SREBP-2. Collectively, CM3I and CM3II are different from the previously reported polysaccharides from C. militaris, and CM3II has a potential application in hypolipidemia and anti-atherosclerosis.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.083DOI Listing
June 2021

SMURF1-mediated ubiquitylation of SHP-1 promotes cell proliferation and invasion of endometrial stromal cells in endometriosis.

Ann Transl Med 2021 Mar;9(5):362

Department of Gynaecology and Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University, Shanghai, China.

Background: Endometriosis is a widespread benign gynecological disorder. The signal transducer and activator of transcription 3 (STAT3) signaling pathway plays an important role in the pathogenesis of endometriosis through regulating proliferation and invasion of endometrial stromal cells. Furthermore, the protein tyrosine phosphatase (PTP), SH2 domain-containing phosphatase 1 (SHP-1), negatively regulates STAT3 activation. However, regulation of the SHP-1-STAT3 pathway in the pathogenesis of endometriosis remains unclear.

Methods: Cell proliferation and invasion were assessed by Cell Counting Kit-8 (CCK-8) assay and Transwell analysis, respectively, to investigate the role and regulation of the SHP-1-STAT3 pathway in the proliferation and invasion of endometrial stromal cells. Expression of Smad ubiquitin regulatory factor 1 (SMURF1), SHP-1, matrix metalloproteinase 2 (MMP2), MMP9, STAT3, and phospho-STAT3 (p-STAT3) level in patients with endometriosis were measured by Western blotting and/or immunohistochemical staining. The interaction between SMURF1 and SHP-1 was investigated by co-immunoprecipitation and ubiquitylation analysis.

Results: The present study demonstrated that downregulation of SHP-1 expression in patients with endometriosis was negatively correlated with SMURF1 expression. SMURF1, an E3 ubiquitin ligase, activated the STAT3 pathway via ubiquitylation and degradation of SHP-1. Furthermore, SMURF1 promoted cell proliferation and invasion of endometrial stromal cells by activating STAT3 signaling and expression of its downstream targets, MMP2 and MMP9, whereas SHP-1 demonstrated an inverse effect. Additionally, SHP-1 inhibited SMURF1-mediated cell invasion and proliferation of endometrial stromal cells.

Conclusions: Our findings indicate that SMURF1-mediated ubiquitylation of SHP-1 regulates endometrial stromal cell proliferation and invasion during endometriosis.
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http://dx.doi.org/10.21037/atm-20-2897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033391PMC
March 2021

miRNA Mediated Regulation and Interaction between Plants and Pathogens.

Int J Mol Sci 2021 Mar 13;22(6). Epub 2021 Mar 13.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing 100083, China.

Plants have evolved diverse molecular mechanisms that enable them to respond to a wide range of pathogens. It has become clear that microRNAs, a class of short single-stranded RNA molecules that regulate gene expression at the transcriptional or post-translational level, play a crucial role in coordinating plant-pathogen interactions. Specifically, miRNAs have been shown to be involved in the regulation of phytohormone signals, reactive oxygen species, and gene expression, thereby modulating the arms race between hosts and pathogens. Adding another level of complexity, it has recently been shown that specific lncRNAs (ceRNAs) can act as decoys that interact with and modulate the activity of miRNAs. Here we review recent findings regarding the roles of miRNA in plant defense, with a focus on the regulatory modes of miRNAs and their possible applications in breeding pathogen-resistance plants including crops and trees. Special emphasis is placed on discussing the role of miRNA in the arms race between hosts and pathogens, and the interaction between disease-related miRNAs and lncRNAs.
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http://dx.doi.org/10.3390/ijms22062913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999934PMC
March 2021

Quantitative CT assessment by histogram and volume ratio in pyrrolizidines alkaloids-induced hepatic sinusoidal obstruction syndrome.

Eur J Radiol 2021 May 6;138:109632. Epub 2021 Mar 6.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Objective: To quantitatively assess hypoattenuation volume ratio and hepatic parenchymal hypoattenuation on contrast enhanced computed tomography (CECT) in patients with pyrrolizidines alkaloids (PAs)-induced hepatic sinusoidal obstruction syndrome (HSOS), and evaluate the correlations of the CT-based quantitative values with clinical factors.

Methods: Thirty-five patients with PAs-induced HSOS who underwent CECT were retrospectively enrolled. The ratio of hypoattenuation volume to total liver volume, and changes in damaged area-to-normal liver density ratio (ΔDR) derived from histogram on portal venous phase were quantitatively measured. Heterogeneous hypoattenuation (CT score) scored by hypoattenuation volume ratio and ΔDR were calculated. The correlation between imaging findings and clinical factors was analyzed using Pearson correlation test.

Results: Liver function tests were abnormal in most patients, the mean Hounsfield unit (HU) of damaged area (58.68 ± 17.3) was significantly lower (P < 0.001) than the corresponding normal liver (82.27 ± 23.97). Heterogeneous hypoattenuation were mild in 13 patients (37 %), moderate in 16 patients (46 %), and severe in 6 patients (17 %). ΔDR derived from histogram was positively correlated (weakly to moderately) with total bilirubin (r = 0.341, P = 0.045), direct bilirubin (r = 0.385, P = 0.022), and alkaline phosphatase (r = 0.491, P = 0.003), while such correlation was not observed in hypoattenuation volume ratio. The severity of heterogeneous hypoattenuation scored by hypoattenuation volume ratio and ΔDR was positively correlated (weakly) with prothrombin time (r = 0.357, P = 0.035), international normalized ratio (r = 0.363, P = 0.032), alkaline phosphatase (r = 0.359, P = 0.034), and model for end-stage liver disease (MELD) score (r = 0.347, P = 0.041).

Conclusion: Heterogeneous hypoattenuation scored by volume ratio and ΔDR on CECT provides a non-invasive approach in evaluating the severity of PAs-induced HSOS.
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http://dx.doi.org/10.1016/j.ejrad.2021.109632DOI Listing
May 2021

Purification, structural characterization, and PCSK9 secretion inhibitory effect of the novel alkali-extracted polysaccharide from Cordyceps militaris.

Int J Biol Macromol 2021 May 1;179:407-417. Epub 2021 Mar 1.

Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China. Electronic address:

One novel alkali-extracted polysaccharide, CM3-SII, was obtained from the fruiting body of C. militaris via column chromatography. Its structural characteristics were investigated via chemical and spectroscopic methods. The backbone of CM3-SII was composed of →4)-β-D-Manp(1→, →6)-β-D-Manp(1→, and →6)-α-D-Manp(1→ glycosyls, and branching at the O-4 positions of →6)-β-D-Manp(1→ glycosyls with β-D-Galp, (1→2) linked-β-D-Galf, and →2,6)-α-D-Manp(1→ residues. Furthermore, O-6 and O-2 positions of the →2,6)-α-D-Manp(1→ residues were substituted with methyl and β-D-Galp, respectively. This polysaccharide significantly enhanced the intracellular protein expression of low-density lipoprotein receptor and proprotein convertase subtilisin/kexin type 9 (PCSK9) via regulating sterol regulatory element-binding protein 2 in hepatoma Huh7 cells. Of note, CM3-SII significantly decreased PCSK9 secretion at the concentration of 200 μg/mL. Collectively, CM3-SII is different from the previously reported alkali-extracted polysaccharides isolated from the fruiting body of C. militaris, and it may have potential application in hypolipidemia or as a pharmaceutical additive.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.191DOI Listing
May 2021

Prognostic factors for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome: a multicenter study in China.

Ann Transl Med 2021 Jan;9(1):11

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: In China, one of the major causes of hepatic sinusoidal obstruction syndrome (HSOS) is the intake of herbals containing pyrrolizidine alkaloid (PA). However, prognostic factors for PA-induced HSOS are poorly understood. The aim of this study was to identify the independent prognostic factors for PA-induced HSOS using a multi-center study.

Methods: A total of 117 PA-induced HSOS patients were enrolled for data collection in three university hospitals from November 2003 to September 2018. Univariate and multivariate Cox proportional hazards analysis were used to determine prognostic factors for PA-induced HSOS.

Results: The median age of the PA-induced HSOS patients was 61 years (range, 21-88 years), and 64% of them were male. The survival rates at 1, 3, and 36 months were 89.71%, 72.60%, and 69.19%, respectively. Significant differences in prothrombin time (PT), international normalized ratio, total bilirubin, severity grading [new criteria for severity grading of hematopoietic stem cell transplantation (HSCT)-related HSOS in adults] were found between patients who survived and those who died. Univariate and multivariate survival analysis using Cox's regression model demonstrated low serum albumin (<35 g/L), elevated serum urea (>8.2 mmol/L) and severe or very severe HSOS (European Society for Blood and Marrow Transplantation 2016 criteria) were independent prognostic factors of survival.

Conclusions: Serum albumin, serum urea, and severity grading were independent prognostic factors for patients with PA-induced HSOS, and can contribute to identifying potentially high-risk patients for early effective intervention.

Trial Registration: ChiCTR-DRD-17010709 (www.chictr.org.cn).
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http://dx.doi.org/10.21037/atm-20-731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859749PMC
January 2021

Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets.

Sci China Life Sci 2021 Jan 19. Epub 2021 Jan 19.

Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Kidney is a major target organ in both antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis (APSN-LN) is intricate and remains largely unrevealed. We proposed in present work, that generation of antiphospholipid antibodies (aPLs), especially those directed towards the oxidized neoepitopes, are largely linked with the redox status along with disease progression. Moreover, we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZW×BXSB F1 mice suffered from APSN-LN. SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties. In current study, we elaborated the therapeutic benefits of SM934 in male NZW×BXSB F1 mice, a murine model develops syndrome resembled human APS associated with SLE, for the first time. SM934 treatment comprehensively impeded autoantibodies production, inflammatory cytokine accumulation and excessive oxidative stress in kidney. Among others, we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets. Collectively, our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.
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http://dx.doi.org/10.1007/s11427-020-1840-1DOI Listing
January 2021

DZ2002 alleviates psoriasis-like skin lesions via differentially regulating methylation of GATA3 and LCN2 promoters.

Int Immunopharmacol 2021 Feb 4;91:107334. Epub 2021 Jan 4.

Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang, Shanghai 201203, China; University of Chinese Academy of Sciences, NO.19A Yuquan Road, Beijing 100049, China; Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Psoriasis is the most prevalent inflammatory skin disorders, affecting 1-3% of the worldwide population. We previously reported that topical application of methyl 4-(adenin-9-yl)-2-hydroxybutanoate (DZ2002), a reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor, was a viable treatment in murine psoriatic skin inflammation. In current study, we further explored the mechanisms of DZ2002 on keratinocyte dysfunction and skin infiltration, the key pathogenic events in psoriasis. We conducted genome-wide DNA methylation analysis in skin tissue from imiquimod (IMQ)-induced psoriatic and normal mice, demonstrated that topical administration of DZ2002 directly rectified aberrant DNA methylation pattern in epidermis and dermis of psoriatic skin lesion. Especially, DZ2002 differentially regulated DNA methylation of GATA3 and LCN2 promoters, which maintained keratinocytes differentiation and reduced inflammatory infiltration in psoriatic skin respectively. In vitro studies in TNF-α/IFN-γ-elicited HaCaT manifested that DZ2002 treatment rectified compromised keratinocyte differentiation via GATA3 enhancement and abated chemokine expression by reducing LCN2 production under inflammatory stimulation. Chemotaxis assays conducted on dHL-60 cells confirmed that suppression of LCN2 expression by DZ2002 was accompanied by CXCR1 and CXCR2 downregulation, and contributed to the inhibition of CXCL8-driven neutrophils migration. In conclusion, therapeutic benefits of DZ2002 are achieved through differentially regulating DNA methylation of GATA3 and LCN2 promoters in psoriatic skin lesion, which efficiently interrupt the pathogenic interplay between keratinocytes and infiltrating immune cells, thus maintains epidermal keratinocytes differentiation and prevents dermal immune infiltration in psoriatic skin.
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http://dx.doi.org/10.1016/j.intimp.2020.107334DOI Listing
February 2021

The complete mitochondrial genome of a Green macroalgae species: (Ulvales: Ulvaceae).

Mitochondrial DNA B Resour 2020 Jan 21;5(1):760-761. Epub 2020 Jan 21.

College of Marine Ecology and Environment, Shanghai Ocean University, Shanghai, China.

a green macroalgae, is one of the causal species for green tides in Japan and spread into the coast of China. During this research, we sequenced the complete mitochondrial genome of . The mitogenome is 62,887 bp in length, including 28 encoding genes and 29 tRNA genes. Compared with the species from mitogenome, the gene order and organization of this mitogenome are similar to most of other determined mitogenomes, with the nucleotide base composition of A 33.6%, T 32.2%, C 16.2%, and G 18.0%. Phylogenetic analysis shows is closely related to .
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http://dx.doi.org/10.1080/23802359.2020.1715856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748431PMC
January 2020

The effects of umbilical cord-derived macrophage exosomes loaded with cisplatin on the growth and drug resistance of ovarian cancer cells.

Drug Dev Ind Pharm 2020 Jul 16;46(7):1150-1162. Epub 2020 Jun 16.

Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai, China.

To assess the feasibility of an exosome-based drug delivery platform for the potent chemotherapeutic agent cisplatin to treat ovarian cancer. Exosomes have recently been used as drug delivery vehicles because of their natural advantages. Platinum-resistant forms of ovarian cancer require novel drug delivery methods to improve patient outcomes. We developed and compared different methods of loading exosomes released by mononuclear M1 and M2 macrophages from umbilical cord blood with cisplatin. We characterized the morphology, drug capacity, method of cellular entry, and antitumor efficacy of the exosomes . Disruption of the exosomal membrane by sonication facilitated a high loading efficiency. Importantly, incorporation of cisplatin into umbilical cord blood-derived M1 macrophage exosomes increased its cytotoxicity 3.3× in drug-resistant A2780/DDP cells and 1.4× in drug-sensitive A2780 cells over chemotherapy alone. Loading of cisplatin into M2 exosomes increased its cytotoxicity by nearly 1.7× in drug-resistant A2780/DDP cells and 1.4× in drug-sensitive A2780 cells. We conclude that cisplatin-loaded M1 exosomes are potentially powerful new tools for the delivery of chemotherapeutics to treat cancers regardless of drug resistance.
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http://dx.doi.org/10.1080/03639045.2020.1776320DOI Listing
July 2020

Efficient Identification for Alcohol Homologues and Hyperthermy Based on Coordination Polymer Multiple Structural Transformations.

ACS Appl Mater Interfaces 2020 May 13;12(21):24141-24148. Epub 2020 May 13.

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

Recently, coordination polymer materials are of high interest due to the potential applications for chemical sensing and luminescent materials. In this work, we designed a photofluorescence coordination polymer material based on a donor-metal-acceptor structure. The donor-metal-acceptor architecture showed unusual multiple environmental responsiveness accompanied by a great change of fluorescence behaviors. Generally, organic homologue molecules are not easily distinguished by coordination polymer sensors because they have similar molecular structures and interaction sites. However, using the feature of multiple structural transformations, the accurate identification for organic homologue molecules can be realized, especially in a short time to quickly identify MeOH in other alcohol homologues (even in mixed atmospheres with only 10% MeOH). The visualization transformation of fluorescence can also be realized by single crystal to single crystal thermal-induced coordination bond ON/OFF behavior. The reversible structure conversion strategy provides new ideas for the accurate identification of organic homolog molecules or external environmental stimuli.
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http://dx.doi.org/10.1021/acsami.0c05208DOI Listing
May 2020

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis.

Cell Death Dis 2020 04 24;11(4):271. Epub 2020 Apr 24.

Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China.

Ulcerative colitis (UC) is a chronic and etiologically refractory inflammatory gut disorder. Although berberine, an isoquinoline alkaloid, has been revealed to exert protective effects on experimental colitis, the underlying molecular mechanism in chronic intestinal inflammation remains ill-defined. This study was designed to uncover the therapeutic efficacy and immunomodulatory role of berberine in chronic UC. Therapeutic effects of oral administration of berberine were investigated in dextran sodium sulfate (DSS)-induced murine chronic UC and the underlying mechanisms were further identified by si-OSMR transfection in human intestinal stromal cells. Berberine significantly attenuated the experimental symptoms and gut inflammation of chronic UC. Berberine treatment could also maintain the intestinal barrier function and rectify tissue fibrosis. In accordance with infiltrations of antigen-presenting cells (APCs), innate lymphoid cells (ILCs), and activated NK cells in colonic lamina propria, increased expression of OSM and OSMR were observed in the inflamed tissue of chronic UC, which were decreased following berberine treatment. Moreover, berberine inhibited the overactivation of human intestinal stromal cells through OSM-mediated JAK-STAT pathway, which was obviously blocked upon siRNA targeting OSMR. The research provided an infusive mechanism of berberine and illustrated that OSM and OSMR intervention might function as the potential target in chronic UC.
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http://dx.doi.org/10.1038/s41419-020-2470-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181765PMC
April 2020

HVEM/HIF-1α promoted proliferation and inhibited apoptosis of ovarian cancer cells under hypoxic microenvironment conditions.

J Ovarian Res 2020 Apr 20;13(1):40. Epub 2020 Apr 20.

Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Our previous studies showed the expression of herpes virus entry mediator (HVEM) is high in ovarian cancer samples and correlated to the patient clinic pathological features. As we all know, the hypoxic environment is the main feature of tumor. In this work, we explored the role of HVEM in hypoxic ovarian cancer cells and its effects on HIF-1α, a transcription factor responding to hypoxia.

Methods: The expression of HVEM, HIF-1α and apoptosis-related genes was detected by qRT-PCR and western blot. The proliferation and apoptosis of the ovarian cancer cells were determined with the Cell Counting Kit-8 assay and AnnexinV-FITC/PI-stained flow cytometry assay, respectively.

Results: The expression of HVEM was positively correlated to that of HIF-1α. The expression of HVEM and HIF-1α under hypoxic conditions was higher than that under normoxic conditions, which suggested that the level of HVEM and HIF-1α correlates with prolonged periods of hypoxia in ovarian cancer. The overexpression of HVEM promoted cell proliferation and inhibited cell apoptosis under hypoxic condition. HVEM overexpression elevated the expression of HIF-1α and Bcl-2 (anti-apoptotic protein), and reduced the expression of Bax (pro-apoptotic protein). In addition, overexpression of HVEM activated the AKT/mTOR signaling. Moreover, knockdown of HVEM had the completely opposite effects.

Conclusion: These data indicated that HVEM signaling might promote HIF-1α activity via AKT/mTOR signaling pathway and thus to regulate tumor growth in ovarian cancer under the hypoxic conditions. Furthermore, these findings indicate that this molecular mechanism could represent a therapeutic target for ovarian cancer.
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http://dx.doi.org/10.1186/s13048-020-00646-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168979PMC
April 2020

DC591017, a phosphodiesterase-4 (PDE4) inhibitor with robust anti-inflammation through regulating PKA-CREB signaling.

Biochem Pharmacol 2020 07 3;177:113958. Epub 2020 Apr 3.

Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Phosphodiesterase-4 (PDE4) functions as a critical intracellular enzyme in immune cells and keratinocytes through the hydrolysis of cAMP. Inhibition of PDE4 has been considered as an effective therapeutic strategy in multiple inflammatory diseases. This study was intended to assess the anti-inflammatory effects of the PDE4 inhibitor, DC591017, both in vitro and in vivo. Murine RAW264.7 cells, BMDMs, BMDCs, and human NHEKs were incubated with DC591017 and then inflammatory mediators, intracellular cAMP and cAMP-mediated signaling pathways were analyzed. Carrageenan-induced acute inflammation in murine air pouches and rat paws, as well as imiquimod (IMQ)-induced psoriasis-like skin lesions were conducted to explore the therapeutic effects and underlying mechanisms of DC591017. We demonstrated herein that DC591017 suppressed the inflammatory responses of macrophages and DCs through promoting cAMP-dependent PKA-CREB signaling. Addition of forskolin functioned synergistically with DC591017, which could be blocked following H89 intervention or knockdown of PKA expression by siRNA transfection. In vivo, DC591017 treatment alleviated the leukocytes infiltration and secretion of inflammatory cytokines in murine air pouches and significantly attenuated carrageenan-induced paw swelling in rats. Moreover, we also illustrated that topical application of DC591017 ointment ameliorated IMQ-caused experimental psoriatic skin lesions, as evidenced by decreasing epidermal thickening and inflammatory infiltrations to inflamed skins. Consistently, DC591017 decreased expression of PDE4 isoforms and subsequently regulated PKA-CREB and NF-κB signaling. In brief, our study brought out a patent PDE4 inhibitor with robust anti-inflammation and provided the credible evidence in the treatment of patients with psoriasis.
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http://dx.doi.org/10.1016/j.bcp.2020.113958DOI Listing
July 2020

Efficacy of Chinese Herbal Formula Sini Zuojin Decoction in Treating Gastroesophageal Reflux Disease: Clinical Evidence and Potential Mechanisms.

Front Pharmacol 2020 27;11:76. Epub 2020 Feb 27.

Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Based on 122 cases reported in China, data mining indicated that Sini Powder (SNP) and the Zuojin Pill (ZJP) are both widely used as the basic recipe for treating Gastroesophageal Reflux Disease (GERD).

Objectives: To evaluate the intervention effects of Sini Zuojin Decoction (SNZJD) in patients with GERD.

Methods: A comprehensive collection of randomized controlled trials (RCTs) using SNZJD in patients with GERD that were published in domestic and foreign journals was made by computer retrieval. RevMan 5.3 software was used for meta-analysis and bias risk assessment, Stata 14.0 software was used for sensitivity analysis, GRADE profiler 3.6 was used to evaluate the level of evidence, and trial sequential analysis (TSA), employed to control for random errors, was performed to assess the main outcomes. Network pharmacology analysis was applied to preliminarily study the mechanisms of action of SNZJD on GERD.

Results: Thirteen articles were eventually included, covering a total of 966 patients. Meta-analysis indicated that: ① the SNZJD plus traditional stomach medicines (SPTSM) group was more effective than the traditional stomach medicines (TSM) group (RR = 1.16, 95% CI [1.04, 1.29], P = 0.009); ② the experimental group with SNZJD was significantly better than TSM controls in improving heartburn, substernal chest pain, acid regurgitation, and food regurgitation symptoms (P < 0.0001); ③ SPTSM could significantly decrease total symptom scores with substantial effectiveness (P < 0.00001). The recurrence rate and adverse effects of SNZJD treatment were significantly reduced (P < 0.05). TSA showed that the effective rate of meta-analysis might be reliable, but the recurrence and safety results were still uncertain. According to the evaluation by the GRADE method, the quality of evidence was low. Besides, SNZJD might treat GERD by acting on related targets and pathways such as inflammation, hormone regulation, and so on.

Conclusions: SNZJD might be useful in the treatment of GERD, but its long-term effects and specific clinical mechanisms are unclear. Due to the poor quality of the evidence, more samples and high-quality clinical studies should be tested and verified in the future.
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http://dx.doi.org/10.3389/fphar.2020.00076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057234PMC
February 2020

Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions.

Acta Pharm Sin B 2020 Mar 5;10(3):447-461. Epub 2019 Sep 5.

Laboratory of Anti-inflammation and Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Ulcerative colitis (UC) manifests as an etiologically complicated and relapsing gastrointestinal disease. The enteric nervous system (ENS) plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract. Berberine, an isoquinoline alkaloid, is known as its anti-inflammatory and therapeutic effects in experimental colitis. However, little research focused on its regulatory function on ENS. Therefore, we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro-immune interactions. Functional defects of enteric glial cells (EGCs), with decreased glial fibrillary acidic protein (GFAP) and increased substance P expression, were observed in DSS-induced murine UC. Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC, closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation. , berberine showed direct protective effects on monoculture of EGCs, bone marrow-derived dendritic cells (BMDCs), T cells, and intestinal epithelial cells (IECs) in the simulated inflammatory conditions. Furthermore, berberine could modulate gut EGCs-IECs-immune cell interactions in the co-culture systems. In summary, our study indicated the EGCs-IECs-immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.
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http://dx.doi.org/10.1016/j.apsb.2019.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049614PMC
March 2020

Ezetimibe promotes CYP7A1 and modulates PPARs as a compensatory mechanism in LDL receptor-deficient hamsters.

Lipids Health Dis 2020 Feb 8;19(1):24. Epub 2020 Feb 8.

Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, 7166# Baotongxi Street, Weifang, 261053, Shandong Province, China.

Background: The LDL-C lowering effect of ezetimibe has been attributed primarily to increased catabolism of LDL-C via up-regulation of LDL receptor (LDLR) and decreased cholesterol absorption. Recently, ezetimibe has been demonstrated to have reverse cholesterol transport (RCT) promoting effects in mice, hamsters and humans. However, the underlying mechanisms are still not clear. The aim of this study is to investigate whether ezetimibe improves RCT-related protein expression in LDLR hamsters.

Methods: A high-fat diet was used to induce a human-like hyperlipidemia in LDLR hamsters. Lipid profiles were assayed by commercially available kits, and the effects of ezetimibe on lipid metabolism-related protein expression were carried out via western blot.

Results: Our data demonstrated that ezetimibe administration significantly reduced plasma total cholesterol (~ 51.6% reduction, P < 0.01) and triglyceride (from ~ 884.1 mg/dL to ~ 277.3 mg/dL) levels in LDLR hamsters fed a high-fat diet. Ezetimibe administration (25 mg/kg/d) significantly promoted the protein expression of cholesterol 7 alpha-hydroxylase A1 (CYP7A1), LXRβ and peroxisome proliferator-activated receptor (PPAR) γ; and down-regulated the protein expression of PPARα and PPARβ. However, it showed no significant effect on sterol regulatory element-binding protein (SREBP)-1c, SREBP-2, proprotein convertase subtilisin/kexin type 9 (PCSK9), Niemann-Pick C1-like 1 (NPC1L1), and ATP-biding cassette (ABC) G5/G8.

Conclusion: Ezetimibe may accelerate the transformation from cholesterol to bile acid via promoting CYP7A1 and thereby enhance RCT. As a compensatory mechanism of TG lowering, ezetimibe promoted the protein expression of PPARγ and decreased PPARα and β. These results are helpful in explaining the lipid-lowering effects of ezetimibe and the potential compensatory mechanisms.
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http://dx.doi.org/10.1186/s12944-020-1202-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007651PMC
February 2020

Clinical characteristics, CT signs, and pathological findings of Pyrrolizidine alkaloids-induced sinusoidal obstructive syndrome: a retrospective study.

BMC Gastroenterol 2020 Feb 4;20(1):30. Epub 2020 Feb 4.

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: One major etiology of hepatic sinusoidal obstruction syndrome (HSOS) in China is the intake of pyrrolizidine alkaloids (PAs). Since PAs-induced HSOS is a rare disease that has not been clearly characterized until now, the aim of this study was to investigate clinical characteristics, CT features, and pathological findings of PA-induced HSOS.

Methods: This retrospective cohort study included 116 patients with PAs-induced HSOS and 68 patients with Budd-Chiari syndrome from Jan 2006 to Sep 2016. We collected medical records of the patients, and reviewed image features of CT, and analyzed pathological findings.

Results: Common clinical manifestations of PAs-induced HSOS were abdominal distention (98.26%), ascites (100%), jaundice (52.94%), abdominal pain (36.36%). Abnormal liver function was observed in most of PAs-induced HSOS. On CT scan, common findings included: ascites, hepatomegaly, the thickening of gallbladder wall, pleural effusion, patchy liver enhancement, and heterogeneous hypoattenuation. Most of the patients had a low ascitic total protein (< 25 g/L) and a high SAAG (≥ 11.0 g/L). In acute stage, pathologic features were massive sinusoidal dilatation, sinusoidal congestion, the extravasation of erythrocytes, hepatocellular necrosis, the accumulation of macrophages, the deposition of hemosiderin. In subacute stage, complete loss of pericentral hepatocytes, sinusoidal dilatation, the deposition of pigment granules were observed.

Conclusions: The PAs-induced HSOS patients displayed distinct clinical characteristics, imaging features, and pathological findings, which provided some evidences for the diagnosis of PAs-induced HSOS.

Trial Registration: ChiCTR-DRD-17010709.
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http://dx.doi.org/10.1186/s12876-020-1180-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001201PMC
February 2020

Astragalus Polysaccharide Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Oxidative Damage and Mitochondrial Dysfunction.

Biomed Res Int 2020 3;2020:2851349. Epub 2020 Jan 3.

Molecular Cell Laboratory for Kidney Disease, Department of Nephrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Pudong New District, Shanghai, China.

Cisplatin is a widely used chemotherapeutic drug in the treatment of various solid tumors. However, the cisplatin-induced acute kidney injury remains a disturbing complication, which still lacks effective prevention. Cisplatin-induced oxidative damage and mitochondrial dysfunction are anticipated to be crucial in the occurrence of kidney injury. Astragalus polysaccharide (APS) has been reported to possess multiple biological activities including anti-inflammatory, antioxidant, and mitochondria protection. In this study, we investigated the potentially protective effect of APS against cisplatin-induced kidney injury both in vivo and in vitro. We found that APS pretreatment attenuated the cisplatin-induced renal dysfunction and histopathological damage in mice; in addition, it also protected the viability of HK-2 cells upon cisplatin exposure. APS attenuated the cisplatin-induced oxidative damage by reducing reactive oxygen species (ROS) generation and recovering the activities of total superoxide dismutase and glutathione peroxidase in mice kidney. In addition, electron microscope analysis indicated that cisplatin induced extensive mitochondrial vacuolization in mice kidney. However, APS administration reversed these mitochondrial morphology changes. In HK-2 cells, APS reduced the cisplatin-induced mitochondrial and intracellular ROS generation. Furthermore, APS protected the normal morphology of mitochondria, blocked the cisplatin-induced mitochondrial permeability transition pore opening, and reduced the cytochrome leakage. Subsequently, APS reduced the cisplatin-induced apoptosis in mice renal and HK-2 cells. In conclusion, our data suggested that APS pretreatment might prevent cisplatin-induced kidney injury through attenuating oxidative damage, protecting mitochondria, and ameliorating mitochondrial-mediated apoptosis.
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http://dx.doi.org/10.1155/2020/2851349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970487PMC
September 2020

An active domain HF-18 derived from hagfish intestinal peptide effectively inhibited drug-resistant bacteria in vitro/vivo.

Biochem Pharmacol 2020 02 6;172:113746. Epub 2019 Dec 6.

School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China. Electronic address:

Antibiotic resistance is spreading faster than the development of new antibiotics into clinical practice. Currently, the design of antimicrobial peptides (AMPs), potential new antibacterial agents with rare antimicrobial resistance, is the available strategy to enhance the antimicrobial activity and lower the toxicity of AMPs. In this study, a peptide derived from hagfish intestinal peptide was designed and termed as HF-18 (GFFKKAWRKVKKAFRRVL). After antimicrobial/bactericidal test in vitro, we found that HF-18 exhibited a potent antimicrobial activity with MIC of only 4 μg/ml against drug-resistant Staphylococcus aureus (S. aureus). Meanwhile, it eliminated the test bacteria within 1 h, suggesting its rapid bactericidal effect. Importantly, this peptide had no obvious hemolytic activity and cytotoxicity to mammalian cells. Furthermore, its notable antimicrobial effects in vivo was confirmed again in S. aureus induced mouse bacteremia and skin wound infection, reflecting as the decrease in bacterial counts in mouse lung or skin (up to 1.9 or 3.5 log CFU respectively), and including the inhibitory activity on inflammatory cytokines secretion. The possible mechanisms underlying HF-18 against drug-resistant S. aureus may attribute that HF-18 neutralized the negative charge in S. aureus surface and then disrupted the integrity of cell membranes to enhance the permeation of bacterial membrane, showing as the increased uptake of NPN and PI and the obvious morphology changes of S. aureus. In addition, this peptide bound to bacterial genomic DNA to suppress the expression of Panton-Valentine leukocidin (pvl) and nuclease (nuc) genes, which play major roles in S. aureus virulence. The properties of HF-18 suggest a path towards developing antibacterial agents that has stronger antibacterial activity and greater security for clinical treatment of infection induced by S. aureus, especially drug-resistant S. aureus.
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http://dx.doi.org/10.1016/j.bcp.2019.113746DOI Listing
February 2020

The fucoidan from the brown seaweed Ascophyllum nodosum ameliorates atherosclerosis in apolipoprotein E-deficient mice.

Food Funct 2019 Aug 31;10(8):5124-5139. Epub 2019 Jul 31.

Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China.

Hyperlipidemia is a major cause of atherosclerosis. Reverse cholesterol transport (RCT) is believed to attenuate hyperlipidemia and the progression of atherosclerosis. Although fucoidans are reported to have hypolipidemic effects, the underlying mechanisms are unclear. Furthermore, few reports have revealed the anti-atherosclerotic effects and the underlying mechanisms of fucoidans. This study was designed to investigate the anti-atherosclerotic effect and mechanisms of the fucoidan from seaweed A. nodosum. Our results demonstrated that the fucoidan administration ameliorated atherosclerotic lesion and lipid profiles in a dose-dependent manner in the apolipoprotein E-deficient (apoE) mice fed a high-fat diet. In the apoE mice liver, the fucoidan treatment significantly increased the expression of scavenger receptor B type 1 (SR-B1), peroxisome proliferator-activated receptor (PPAR) α and β, liver X receptor (LXR) α, ATP-binding cassette transporter (ABC) A1 and ABCG8; and markedly decreased the expression of PPARγ and sterol regulatory element-binding protein (SREBP) 1c, but not low-density lipoprotein receptor, proprotein convertase subtilisin/kexin type 9, cholesterol 7 alpha-hydroxylase A1, LXRβ and ABCG1. In the small intestine of the apoE mice, the fucoidan treatment significantly reduced the expression of Niemann-Pick C1-like 1 (NPC1L1) and dramatically improved ABCG8 levels. These results demonstrated for the first time that the fucoidan from A. nodosum attenuated atherosclerosis by regulating RCT-related genes and proteins expression in apoE mice. In summary, this fucoidan from A. nodosum may be explored as a potential compound for prevention or treatment of hyperlipidemia-induced atherosclerosis.
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http://dx.doi.org/10.1039/c9fo00619bDOI Listing
August 2019

Dataset of the infrared spectrometry, gas chromatography-mass spectrometry analysis and nuclear magnetic resonance spectroscopy of the polysaccharides from . .

Data Brief 2019 Aug 11;25:104126. Epub 2019 Jun 11.

Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China.

The data presented in this article describe characteristics of the polysaccharides, designated as CM1 and CMS, isolated from the fruiting body of . Fourier transform infrared spectrometry analysis was used to identify the basic characteristics of the polysaccharides and the completeness of methylation. Gas chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy were carried out to reveal the glycosidic linkages of CM1 and CMS. Further interpretation and discussion could be found at our research article entitled "Structural characterisation and cholesterol efflux improving capacity of the novel polysaccharides from " (Hu et al., 2019; https://doi.org/10.1016/j.ijbiomac.2019.03.078) [1].
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http://dx.doi.org/10.1016/j.dib.2019.104126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595413PMC
August 2019

1-calcium phosphate-uracil inhibits intraperitoneal metastasis by suppressing FAK in epithelial ovarian cancer.

Cell Cycle 2019 08 10;18(16):1925-1937. Epub 2019 Jul 10.

a Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine , Shanghai , China.

The high mortality of epithelial ovarian cancer (EOC) is primarily due to vast intraperitoneal dissemination. 1-calcium phosphate-uracil (1-CP-U) has previously shown the function of inhibiting migration and invasion in multiple tumor cell lines. In this study, we further assessed the possible role of 1-CP-U in suppressing the peritoneal metastasis of EOC cells. First, we demonstrated that 1-CP-U had an inhibitory effect on EOC cells in cell-matrix adhesion, migration and invasion assay . Within the model, animals were intraperitoneally inoculated with SKOV3-Luc cells and then 1-CP-U intraperitoneal (.) injection was performed every 5 d for a total of 3 wk. At the 7th d, omenta from each group were analyzed with luciferase activity and bioluminescence imaging assay, which showed a significant reduction of luciferase activity in the omenta from 1-CP-U group. In addition, the rest mice continued treatment and consistent detection of bioluminescence imaging. The data indicated that intraperitoneal metastatic nodules were less-developed in 1-CP-U group. Peritoneal metastatic tumor nodules were detected for immunofluorescent staining, which showed a reduction in FAK and p-FAK staining with 1-CP-U treatment group. Meanwhile, expressions of FAK and its downstream signaling were detected by western blot in tumor tissues and EOC cell lines, which showed significant decreases in the 1-CP-U treatment group. In conclusion, 1-CP-U had a profound inhibitory effect on adhesion, invasion and metastasis of EOC and suppressed intraperitoneal dissemination and cancer growth assay, which was associated with inhibition on the FAK pathway.
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http://dx.doi.org/10.1080/15384101.2019.1634946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681791PMC
August 2019

The fucoidan A3 from the seaweed Ascophyllum nodosum enhances RCT-related genes expression in hyperlipidemic C57BL/6J mice.

Int J Biol Macromol 2019 Aug 14;134:759-769. Epub 2019 May 14.

Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China. Electronic address:

Reverse cholesterol transport (RCT) has been demonstrated to reduce hyperlipidemia, and fucoidans are found to possess hypolipidemic effect. This study was designed to investigate the lipid-lowering effect of the fucoidan from the brown seaweed A. nodosum and whether it improves RCT-related genes expression in C57 BL/6J mice. Our results indicated that fucoidan A3 (100 mg/kg/day) intervention significantly reduced plasma total cholesterol (~23.2%), triglyceride (~48.7%) and fat pad index. This fucoidan significantly increased the mRNA expression of low-density lipoprotein receptor (LDLR), scavenger receptor B type 1 (SR-B1), cholesterol 7 alpha-hydroxylase A1 (CYP7A1), liver X receptor (LXR) β, ATP-binding cassette transporter (ABC) A1 and sterol regulatory element-binding protein (SREBP) 1c, and decreased the expression of peroxisome proliferator-activated receptor (PPAR) γ, however, it had no effect on the expression of proprotein convertase subtilisin/kexin type 9, PPARα, LXRα, SREBP-2, ABCG1, ABCG8 and Niemann-Pick C1-like 1. These results demonstrated that this fucoidan improved lipid transfer from plasma to the liver by activating SR-B1 and LDLR, and up-regulated lipid metabolism by activating LXRβ, ABCA1 and CYP7A1. In conclusion, this fucoidan lowers lipid by enhancing RCT-related genes expression, and it can be explored as a potential candidate for prevention or treatment of lipid disorders.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.05.070DOI Listing
August 2019

Fucoidan A2 from the Brown Seaweed Ascophyllum nodosum Lowers Lipid by Improving Reverse Cholesterol Transport in C57BL/6J Mice Fed a High-Fat Diet.

J Agric Food Chem 2019 May 13;67(20):5782-5791. Epub 2019 May 13.

Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy , Weifang Medical University , Weifang , Shandong 261053 , People's Republic of China.

Reverse cholesterol transport (RCT) is a physiological process, in which excess peripheral cholesterol is transported to the liver and further excreted into the bile and then feces. Recently, fucoidans are reported to have a lipid-lowering effect. This study was designed to investigate whether fucoidan from the brown seaweed Ascophyllum nodosum lowers lipid by modulating RCT in C57BL/6J mice fed a high-fat diet. Our results indicated that fucoidan intervention significantly reduced plasma triglyceride, total cholesterol, and fat pad index and markedly increased high-density lipoprotein cholesterol in a dose-dependent manner. In the liver, fucoidan significantly increased the expression of peroxisome proliferator-activated receptor (PPAR)α, PPARγ, liver X receptor (LXR)β, adenosine triphosphate (ATP) binding cassette (ABC)A1, ABCG8, low-density lipoprotein receptor (LDLR), scavenger receptor B type 1 (SR-B1), and cholesterol 7-α-hydroxylase A1 (CYP7A1) and decreased the triglyceride level and expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and PPARβ but had no effect on LXRα, ABCG1, and ABCG5. In the small intestine, the fucoidan treatment significantly reduced the expression of Niemann-Pick C1-like 1 (NPC1L1) and improved ABCG5 and ABCG8. These results demonstrated that fucoidan can improve lipid transfer from plasma to the liver by activating SR-B1 and LDLR and inactivating PCSK9 and upregulate lipid metabolism by activating PPARα, LXRβ, ABC transporters, and CYP7A1. In the small intestine, this fucoidan can decrease cholesterol absorption and increase cholesterol excretion by activating NPC1L1 and ABCG5 and ABCG8, respectively. In conclusion, fucoidan from A. nodosum may lower lipids by modulating RCT-related protein expression and can be explored as a potential compound for prevention or treatment of hyperlipidemia-related diseases.
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http://dx.doi.org/10.1021/acs.jafc.9b01321DOI Listing
May 2019

Change Detection of Optical Remote Sensing Image Disturbed by Thin Cloud Using Wavelet Coefficient Substitution Algorithm.

Sensors (Basel) 2019 Apr 26;19(9). Epub 2019 Apr 26.

Knowledge Engineering and Discovery Research Institute, Auckland University of Technology, 1020 Auckland, New Zealand.

The detection of changes in optical remote sensing images under the interference of thin clouds is studied for the first time in this paper. First, the optical remote sensing image is subjected to thin cloud removal processing, and then the processed remote sensing image is subjected to image change detection. Based on the analysis of the characteristics of thin cloud images, a method for removing thin clouds based on wavelet coefficient substitution is proposed in this paper. Based on the change in the wavelet coefficient, the high- and low-frequency parts of the remote sensing image are replaced separately, and the low-frequency clouds are suppressed while maintaining the high-frequency detail of the image, which achieves good results. Then, an unsupervised change detection algorithm based on a combined difference graph and fuzzy c-means clustering algorithm (FCM) clustering is applied. First, the image is transformed into a logarithmic domain, and the image is denoised using Frost filtering. Then, the mean ratio method and the difference method are used to obtain two graph difference maps, and the combined difference graph method is used to obtain the final difference image. The experimental results show that the algorithm can effectively solve the problem of image change detection under thin cloud interference.
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http://dx.doi.org/10.3390/s19091972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539379PMC
April 2019