Publications by authors named "Pan Xu"

250 Publications

Highly interconnected inverse opal extracellular matrix scaffolds enhance stem cell therapy in limb ischemia.

Acta Biomater 2021 Apr 17. Epub 2021 Apr 17.

College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China. Electronic address:

The therapeutic effectiveness of cell transplantation in treatment of diseases and injuries is often limited by low cell retention, survivability, and engraftment. Extracellular matrix (ECM)-derived scaffolds are capable of controlling cell responses, thereby offering potential solutions to current challenges associated with cell therapy. However, it remains a technical challenge to produce ECM scaffolds with highly interconnected porous structure specifically required for cell transplantation. Here, we developed inverse opal porous extracellular matrix (ioECM) scaffolds through subcutaneous implantation of sacrificial templates assembled from polymer microspheres, followed by removal of the microsphere template and cellular content. Such highly interconnected porous ioECM scaffolds supported the anchorage, survival, viability, anti-apoptotic and paracrine activities of rat bone marrow mesenchymal stem cells (BMSCs), which further promoted endothelial cell migration and tube formation and viability. Upon transplantation into nude mouse critical limb ischemic model, ioECM promoted the engraftment of laden BMSCs, facilitated interconnected vascular network formation with accelerated recovery of blood perfusion and inhibited muscle atrophy and fibrosis. Our study demonstrates a unique strategy to engineer highly porous yet well-interconnected ECM scaffolds specifically for cell transplantation with marked improvement of survivability and vascularization, which offers an essential step toward the success of cell therapy and regenerative medicine. Statement of Significance: Cell-based therapy has a good developing foreground applied in a variety of tissue regeneration. Extracellular matrix (ECM) scaffolds is an optimal choice for cell delivery duo to its superior biocompatibility and favorable immune responses. However, the current ECM scaffolds lacking of the controllable pore structure restrict the cell delivery efficiency and therapeutic outcome. Here, we fabricated highly interconnected inverse opal extracellular matrix (ioECM) scaffolds, which can enhance the effect of stem cell therapy in limb ischemic model by improving the survival, viability, and paracrine activities of stem cells. Our study provides reference value for the design and fabrication of ECM based biomaterials for cell transplantation.
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http://dx.doi.org/10.1016/j.actbio.2021.04.025DOI Listing
April 2021

Pseudoaneurysm after Common Carotid Artery Atherosclerotic Rupture.

Radiology 2021 Apr 20:203807. Epub 2021 Apr 20.

From the Department of Ultrasonography, First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Road, Nanchang 330006, China.

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http://dx.doi.org/10.1148/radiol.2021203807DOI Listing
April 2021

Efficacy of Microplasma Radiofrequency Versus CO2 Laser Therapy for Seborrheic Keratoses: A Randomized, Intraindividual Comparative Study.

Dermatol Surg 2021 Apr 13. Epub 2021 Apr 13.

Medical School, Nantong University, Jiangsu, China Department of Medical Cosmetology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

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http://dx.doi.org/10.1097/DSS.0000000000002896DOI Listing
April 2021

PRMT1 is a novel molecular therapeutic target for clear cell renal cell carcinoma.

Theranostics 2021 12;11(11):5387-5403. Epub 2021 Mar 12.

Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

Epigenetic alterations are common events in clear cell renal cell carcinoma (ccRCC), and protein arginine methyltransferase 1 (PRMT1) is an important epigenetic regulator in cancers. However, its role in ccRCC remains unclear. We investigated PRMT1 expression level and its correlations to clinicopathological factors and prognosis in ccRCC patients based on ccRCC tissue microarrays (TMAs). Genetic knockdown and pharmacological inhibition using a novel PRMT1 inhibitor DCPT1061 were performed to investigate the functional role of PRMT1 in ccRCC proliferation. Besides, we confirmed the antitumor effect of PRMT1 inhibitor DCPT1061 in ccRCC cell-derived tumor xenograft (CDX) models as well as patient-derived tumor xenograft (PDX) models. We found PRMT1 expression was remarkably upregulated in tumor tissues and associated with poor pathologic characters and outcomes of ccRCC patients. Furthermore, genetic knockdown and pharmacological inhibition of PRMT1 by a novel potent inhibitor DCPT1061 dramatically induced G1 cell cycle arrest and suppressed ccRCC cell growth. Mechanistically, RNA sequencing and further validation identified Lipocalin2 (LCN2), a secreted glycoprotein implicated in tumorigenesis, as a crucial regulator of ccRCC growth and functional downstream effector of PRMT1. Epigenetic silencing of LCN2 autocrine secretion by PRMT1 deficiency decreased downstream p-AKT, leading to reduced p-RB and cell growth arrest through the neutrophil gelatinase associated lipocalin receptor (NGALR). Moreover, PRMT1 inhibition by DCPT1061 not only inhibited tumor growth but also sensitized ccRCC to sunitinib treatment by attenuating sunitinib-induced upregulation of LCN2-AKT-RB signaling. Taken together, our study revealed a PRMT1-dependent epigenetic mechanism in the control of ccRCC tumor growth and drug resistance, indicating PRMT1 may serve as a promising target for therapeutic intervention in ccRCC patients.
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http://dx.doi.org/10.7150/thno.42345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039964PMC
March 2021

Comparative analysis of chloroplast genomes of cultivars and wild species of sweetpotato (Ipomoea batatas [L.] Lam).

BMC Genomics 2021 Apr 13;22(1):262. Epub 2021 Apr 13.

Jiangsu Xuzhou Sweetpotato Research Center/Sweetpotato Research Institute, China Agricultural Academy of Sciences, Xuzhou, 221131, China.

Background: Sweetpotato (Ipomoea batatas [L.] Lam.) is an important food crop. However, the genetic information of the nuclear genome of this species is difficult to determine accurately because of its large genome and complex genetic background. This drawback has limited studies on the origin, evolution, genetic diversity and other relevant studies on sweetpotato.

Results: The chloroplast genomes of 107 sweetpotato cultivars were sequenced, assembled and annotated. The resulting chloroplast genomes were comparatively analysed with the published chloroplast genomes of wild species of sweetpotato. High similarity and certain specificity were found among the chloroplast genomes of Ipomoea spp. Phylogenetic analysis could clearly distinguish wild species from cultivars. Ipomoea trifida and Ipomoea tabascana showed the closest relationship with the cultivars, and different haplotypes of ycf1 could be used to distinguish the cultivars from their wild relatives. The genetic structure was analyzed using variations in the chloroplast genome. Compared with traditional nuclear markers, the chloroplast markers designed based on the InDels on the chloroplast genome showed significant advantages.

Conclusions: Comparative analysis of chloroplast genomes of 107 cultivars and several wild species of sweetpotato was performed to help analyze the evolution, genetic structure and the development of chloroplast DNA markers of sweetpotato.
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http://dx.doi.org/10.1186/s12864-021-07544-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042981PMC
April 2021

Uncovering the Pharmacology of Xiaochaihu Decoction in the Treatment of Acute Pancreatitis Based on the Network Pharmacology.

Biomed Res Int 2021 20;2021:6621682. Epub 2021 Mar 20.

Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310014, China.

Background: Xiaochaihu decoction (XD) has demonstrated the pharmacodynamics on acute pancreatitis. This study was aimed at investigating the material and molecular basis of Xiaochaihu decoction.

Methods: Firstly, compounds of seven herbs containing XD were collected from the TCMSP, ETCM, and BATMAN-TCM databases, and the putative targets of pancreatitis were obtained from the OMIM, TTD, and GeneCards databases. Then, the PPI network was constructed according to the matching results between XD potential targets and pancreatic neoplasm targets. Furthermore, enrichment analysis on GO and KEGG by DAVID utilized bioinformatics resources. Finally, molecular docking was performed to simulate the interaction between the active compound of XD and putative targets. In an experiment, AR42J cells were induced by LPS and then treated with Quercetin (25, 50, and 100 M) or XCHD. The IL-6, TNF-, and IL-1 levels were detected by ELISA kit, and mRNA expressions were measured by qRT-PCR, and the proteins of MAPK3 and TP53 expressions were measured by WB.

Results: A total of 196 active ingredients and 91 putative targets were selected. The PPI network analysis demonstrated that Quercetin was the candidate agent and MAPK3, IL-6, and TP53 were the potential targets for the XD treatment of acute pancreatitis. The KEGG analysis revealed that pathways in cancers, TNF signaling way, and MAPK signaling way might play an important role in pancreatitis therapy. And molecular docking results showed that Quercetin combined well with MAPK3, IL-6, and TP53. An experiment indicated that XCHD and Quercetin inhibited the IL-6, TNF-, and IL-1 levels and MAPK3 and TP53.

Conclusion: This study illustrated that XCHD and Quercetin contained in XD played an important role in the treatment of acute pancreatitis by acting on the key genes of MPAK3, IL-6, and TP53 which were associated with inflammation and apoptosis.
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http://dx.doi.org/10.1155/2021/6621682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007340PMC
March 2021

The presence of P. melaninogenica within tissue and preliminary study on its role in the pathogenesis of oral lichen planus.

Oral Dis 2021 Mar 29. Epub 2021 Mar 29.

Shanghai Engineering Research Center of Tooth Restoration and Regeneration, School of Stomatology, Tongji University, Shanghai, China.

Objective: Oral lichen planus (OLP) is a chronic inflammatory disease that occurs in the oral mucosa with characteristic white striations lesions, recurrent erosions and pains. The etiology and pathogenesis of OLP are still unclear.

Materials And Methods: We analyzed the bacterial community structure of buccal mucosa in patients with OLP and normal controls by high-throughput sequencing. Fluorescence in situ hybridization (FISH) was uesd to detect Prevotella melaninogenica (P. melaninogenica) in 13 OLP samples and 10 controls. The amounts of P. melaninogenica in OLP buccal mucosa and the expression of inflammatory cytokines in co-culture of mouse-derived macrophages with P. melaninogenica were detected by RT-qPCR.

Results: The P. melaninogenica was more abundant in OLP than in healthy controls and the differences were significant at the level of the phylum, family, genus and species (P<0.05). FISH showed that P. melaninogenica can invade the epithelium and even the lamina propria of OLP, while no invasion was found in the normal mucosa. P. melaninogenica can adhere to and invade macrophages and then activate the transcription of IL-1β, IL-6 and TNF-α in NF-κB signaling pathway.

Conclusion: P. melaninogenica may be involved in the pathogenic process of OLP, and its specific mechanism deserves further study.
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http://dx.doi.org/10.1111/odi.13862DOI Listing
March 2021

NOD1 Agonist Protects Against Lipopolysaccharide and D-Galactosamine-Induced Fatal Hepatitis Through the Upregulation of A20 Expression in Hepatocytes.

Front Immunol 2021 4;12:603192. Epub 2021 Mar 4.

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Increasing evidence suggests that NODs are involved in liver diseases; however, the underlying mechanisms remain obscure. In the present study, we analyzed the effect of NOD1 agonist pretreatment on acute liver failure induced by lipopolysaccharide (LPS) in D-galactosamine (D-GalN)-sensitized mice. We found that pretreatment with the NOD1 agonist markedly reduced LPS/D-GalN-induced mortality, elevation of serum ALT levels, and hepatocyte apoptosis. The protective effect of NOD1 agonist was independent of tumor necrosis factor (TNF)-α inhibition. NOD1 agonist pretreatment also attenuated TNF-α/D-GalN-induced apoptotic liver damage. The anti-apoptotic protein A20 expression was more pronounced in NOD1 agonist pretreated mice than in controls, and knockdown of A20 abrogated the protective effect of NOD1 agonist on LPS/D-GalN-induced liver injury and hepatocyte apoptosis. Further experiments showed that NOD1 agonist-induced A20 upregulation required the presence of kupffer cells and TNF-α. Taken together, our data strongly indicate that NOD1 is involved in the regulation of liver injury and could be a potential therapeutic target for liver diseases.
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http://dx.doi.org/10.3389/fimmu.2021.603192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969647PMC
March 2021

Recovering heavy metals from electroplating wastewater and their conversion into ZnCr-layered double hydroxide (LDH) for pyrophosphate removal from industrial wastewater.

Chemosphere 2021 May 6;271:129861. Epub 2021 Feb 6.

Advanced Membrane Technology Research Centre (AMTEC), School of Chemical and Energy Engineering, Universiti Teknologi Malaysia, 81310, Skudai, Johor, Malaysia.

This work incorporated technological values into ZnCr-layered double hydroxide (LDH), synthesized from unused resources, for removal of pyrophosphate (PP) in electroplating wastewater. To adopt a resource recovery for the remediation of the aquatic environment, the ZnCr-LDH was fabricated by co-precipitation from concentrated metals of plating waste that remained as industrial by-products from metal finishing processes. To examine its applicability for water treatment, batch experiments were conducted at optimum M/M, pH, reaction time, and temperature. To understand the adsorption mechanisms of the PP by the adsorbent, the ZnCr-LDH was characterized using Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) analyses before and after adsorption treatment. An almost complete PP removal was attained by the ZnCr-LDH at optimized conditions: 50 mg/L of PP, 1 g/L of adsorbent, pH 6, and 6 h of reaction. Ion exchange controlled the PP removal by the adsorbent at acidic conditions. The PP removal well fitted a pseudo-second-order kinetics and/or the Langmuir isotherm model with 79 mg/g of PP adsorption capacity. The spent ZnCr-LDH was regenerated with NaOH with 86% of efficiency for the first cycle. The treated effluents could comply with the discharge limit of <1 mg/L. Overall, the use of the ZnCr-LDH as a low-cost adsorbent for wastewater treatment has contributed to national policy that promotes a zero-waste approach for a circular economy (CE) through a resource recovery paradigm.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129861DOI Listing
May 2021

Whole-genome SNP markers reveal conservation status, signatures of selection, and introgression in Chinese Laiwu pigs.

Evol Appl 2021 Feb 16;14(2):383-398. Epub 2020 Sep 16.

Guangdong Laboratory for Lingnan Modern Agriculture College of Animal Science South China Agricultural University Guangzhou China.

Laiwu pigs are a Chinese indigenous breed that is renowned for its exceptionally high intramuscular fat content (average greater than 6%), providing an excellent genetic resource for the genetic improvement of meat quality of modern commercial pigs. To uncover genetic diversity, population structure, signature of selection, and potential exotic introgression in this breed, we sampled 238 Laiwu pigs from a state-supported conservation population and genotyped these individuals using GeneSeek 80K SNP BeadChip. We then conducted in-depth population genetics analyses for the Laiwu pig in a context of 1,116 pigs from 42 Eurasian diverse breeds. First, we show that the current Laiwu population has more abundant genetic diversity than the population of 18 years ago likely due to gene flow from European commercial breeds. Both neighbor-joining (NJ) and principal component analyses indicate the introgression of European haplotypes into Laiwu pigs. The admixture analysis reveals that an average 26.66% of Laiwu genetic components are of European origin. Then, we assigned the tested individuals to different families according to their clustering patterns in the NJ tree and proposed a family-based conservation strategy to reduce the risk of inbreeding depression in Laiwu pigs. Next, we explored three statistics (ROH and iHS and EigenGWAS) to identify a list of candidate genes for fat deposition, reproduction, and growth in Laiwu pigs. Last, we detected a strong signature of introgression from European pigs into Laiwu pigs at the locus that regulates the growth of developing long bones. Further association analyses indicate that the introgressed haplotype likely contributed to the improvement of growth performance in Laiwu pigs. Altogether, this study not only benefits the better conservation of the Laiwu pig, but also advances our knowledge of the poorly understood effect of human-mediated introgression on phenotypic traits in Chinese indigenous pigs.
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http://dx.doi.org/10.1111/eva.13124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896721PMC
February 2021

Functioning of PPR Proteins in Organelle RNA Metabolism and Chloroplast Biogenesis.

Front Plant Sci 2021 9;12:627501. Epub 2021 Feb 9.

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

The pentatricopeptide repeat (PPR) proteins constitute one of the largest nuclear-encoded protein families in higher plants, with over 400 members in most sequenced plant species. The molecular functions of these proteins and their physiological roles during plant growth and development have been widely studied. Generally, there is mounting evidence that PPR proteins are involved in the post-transcriptional regulation of chloroplast and/or mitochondrial genes, including RNA maturation, editing, intron splicing, transcripts' stabilization, and translation initiation. The cooperative action of RNA metabolism has profound effects on the biogenesis and functioning of both chloroplasts and mitochondria and, consequently, on the photosynthesis, respiration, and development of plants and their environmental responses. In this review, we summarize the latest research on PPR proteins, specifically how they might function in the chloroplast, by documenting their mechanism of molecular function, their corresponding RNA targets, and their specific effects upon chloroplast biogenesis and host organisms.
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http://dx.doi.org/10.3389/fpls.2021.627501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900629PMC
February 2021

Design, synthesis, and biological evaluation of 4-benzoylamino-1H-pyrazole-3-carboxamide derivatives as potent CDK2 inhibitors.

Eur J Med Chem 2021 Apr 11;215:113281. Epub 2021 Feb 11.

Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing, 100049, China. Electronic address:

Cyclin-dependent kinases play significant roles in cell cycle progression and are promising targets for cancer therapy. However, most potent CDK inhibitors lack the balance between efficacy and safety because of poor selectivity. Given the roles of CDK2 in tumorigenesis, selective CDK2 inhibition may provide therapeutic benefits against certain cancer. In this study, a series of 4-benzoylamino-1H-pyrazole-3-carboxamide derivatives were designed, synthesized, and evaluated. The most selective compound DC-K2in212 in this series exhibited high potency towards CDK2 and had effective anti-proliferative activity against A2058 melanoma cell line and MV4-11 leukemia cell line while exhibiting low toxic effect on human normal cell lines MRC5 and LX2. The molecular modeling illustrated that compound DC-K2in212 had the similar binding mode with CDK2 as C-73, the most selective CDK2 inhibitor reported so far, which might account for selectivity against CDK2 over CDK1. Further biological studies revealed that compound DC-K2in212 suppressed CDK2-associated downstream signaling pathway, blocked cell cycle progression, and induced cellular apoptosis. Therefore, compound DC-K2in212 could serve as a potential CDK2 inhibitor for further development.
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http://dx.doi.org/10.1016/j.ejmech.2021.113281DOI Listing
April 2021

Safety of high-dose in adolescent rats based on metabolomics.

Food Sci Nutr 2021 Feb 1;9(2):794-810. Epub 2020 Dec 1.

Jiangxi University of Traditional Chinese Medicine Nanchang China.

is the dried root of the leguminous plant and is a common component of health products and medicines. Although it is considered safe, some studies have reported that has hepatotoxicity and estrogen-like effects. In this study, the safety of high doses of water extract administered to adolescent rats for 30 days was evaluated by biochemical, histopathological, and metabolomic analyses. Overall, there were no significant differences between the low-dose and blank control groups in parameter values, including organ wet weight, organ coefficient, routine blood indicators, serum biochemical indexes of liver and renal function, levels of estradiol and testosterone, histopathological parameters, and primary differential metabolite profiles. Compared with the blank control group, the high-dose group may have a certain effect on the liver. These effects might be mediated by abnormal phenylalanine, tyrosine, and tryptophan biosynthesis or phenylalanine metabolism. However, histopathological analyses did not show differences in the liver, kidney, breast, uterus, ovary, testis, and epididymis between the control group and the group treated with a high dose of water extract. water extract did not significantly promote the precocity of male and female sexual organs. Overall, water extract is relatively safe for adolescent rats.
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http://dx.doi.org/10.1002/fsn3.2044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866568PMC
February 2021

Interleukin-28A Induces Epithelial Barrier Dysfunction in CD Patient-derived Intestinal Organoids.

Am J Physiol Gastrointest Liver Physiol 2021 Feb 17. Epub 2021 Feb 17.

Internal Medicine-Devision of Gadstroenterolgy and Hepatology, Maastricht University Medical Centre.

Intestinal barrier dysfunction is a pathogenic hallmark in Crohn's disease (CD). Identifying key players that regulate intestinal barrier may provide novel leads for therapeutic intervention. Interleukin-28A (IL-28A) is a newly identified IL-10/interferon cytokine family member, with its most implicated function being antiviral and anti-proliferative properties. However, the role and underlying mechanisms of IL-28A in the regulation of epithelial barrier in CD remain so far unexplored. IL-28A levels were measured in the plasma and biopsies of CD patients and healthy subjects. CD patient-derived intestinal organoids were characterized by differentiation gene markers and then exposed to TNF-α, IFN-γ, IL-1β or LPS, or IL-28A with or without GLPG0634 (filgotinib). Epithelial permeability was assessed by FITC-D4 flux. Expression of junctional components was analyzed by qRT-PCR, immunofluorescence staining or western blotting. JAK-STAT activity was analyzed by western blotting. IL-28A levels were increased in the plasma and biopsies from active CD patients as compared to healthy subjects. IL-28A and its receptor complex IL-28AR/IL-10R2 were detected in CD patient-derived intestinal organoids and showed a selective response to IFN-γ exposure. IL-28A triggered epithelial barrier disruption, accompanied by reduced ZO-1 and E-Cadherin expression. This effect was mediated by JAK-STAT1 pathway. Pre-incubation with the JAK1 inhibitor filgotinib ameliorated the barrier dysfunction induced by IL-28A. These results identified IL-28A as a novel regulator of epithelial barrier function and could be a putative target for CD treatment. We provide novel basic evidence that restoring intestinal barrier is a potential mechanism that contributes to the clinical benefits of JAK1 inhibitor in CD patients.
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http://dx.doi.org/10.1152/ajpgi.00064.2020DOI Listing
February 2021

Corticosteroid enhances epithelial barrier function in intestinal organoids derived from patients with Crohn's disease.

J Mol Med (Berl) 2021 Feb 11. Epub 2021 Feb 11.

Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre+, P. Debyelaan 25 6229 HX, Maastricht, the Netherlands.

Corticosteroids (CS), first-line therapeutics for Crohn's disease (CD) with moderate or severe disease activity, were found to restore intestinal permeability in CD patients, whereas the underlying molecular events are still largely unknown. This study aimed to investigate the effect and mechanisms of CS prednisolone on epithelial barrier using CD patient-derived intestinal organoids. 3D intestinal organoids were generated from colon biopsies of inactive CD patients. To mimic the inflammatory microenvironment, a mixture of cytokines containing TNF-α, IFN-γ, and IL-1β were added to the organoid culture with or without pre-incubation of prednisolone or mifepristone. Epithelial permeability of the organoids was assessed by FITC-D4 flux from the basal to luminal compartment using confocal microscopy. Expression of junctional components were analyzed by qRT-PCR, immunofluorescence staining, and western blot. Activity of signaling pathways were analyzed using western blot. Exposure of the cytokines significantly disrupted epithelial barrier of the intestinal organoids, which was partially restored by prednisolone. On the molecular level, the cytokine mixture resulted in a significant reduction in E-cadherin and ILDR-1, an increase in CLDN-2, MLCK, and STAT1 phosphorylation, whereas prednisolone ameliorated the abovementioned effects induced by the cytokine mixture. This study demonstrates that prednisolone confers a direct effect in tightening the epithelial barrier, identifies novel junctional targets regulated by prednisolone, and underscores intestinal barrier restoration as a potential mechanism that contributes to the clinical efficacy of prednisolone in CD patients. KEY MESSAGES: Prednisolone confers a direct preventive effect against cytokine-induced barrier dysfunction. Prednisolone regulates the expression of CLDN-2, E-cadherin, and ILDR-1. The effect of prednisolone is GR-, MLCK-, and STAT1-dependent.
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http://dx.doi.org/10.1007/s00109-021-02045-7DOI Listing
February 2021

Porous carbon/graphite nanosheet/ferromagnetic nanoparticle composite absorbents with adjustable electromagnetic properties.

Nanotechnology 2021 May;32(20):205707

Alan G. MacDiarmid Institute, Jilin University, 2699 Qianjin Street, Changchun 130012, People's Republic of China.

With the rapid development of electronic devices and wireless communication tools, it is urgent to design and fabricate low-cost, lightweight and effective electromagnetic absorption materials to solve interference of electromagnetic waves. Herein, a new strategy toward porous carbon/graphite nanosheet/ferromagnetic nanoparticle (PC/GNS/Fe) composites was designed to investigate the influence of crystalline carbon on electromagnetic wave absorption. To begin with, graphite nanosheets (GNSs) were incorporated into the porous polyimide by in situ polymerization, and Fe were added as a magnetic particle source and an agent to regulate the pore size. A series of PC/GNS/Fe composite absorbents were obtained. The direct carbonization of porous polymer precursors was beneficial to the design of the pore structure of materials. A hierarchically porous structure derived from the phase separation process was well maintained in the polyimide pyrolysis process. The results demonstrated that the presence of crystalline carbon could influence the reflection loss value and the frequency range. Hence, the absorbing performance can be optimized by adjusting the pore structure and the content of crystalline carbon in materials, which is conducive to obtaining electromagnetic wave absorption materials with excellent comprehensive performance.
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http://dx.doi.org/10.1088/1361-6528/abe3b8DOI Listing
May 2021

A Carbon Foam with Sodiophilic Surface for Highly Reversible, Ultra-Long Cycle Sodium Metal Anode.

Adv Sci (Weinh) 2021 Jan 4;8(2):2003178. Epub 2020 Dec 4.

Collaborative Innovation Center of Chemistry for Energy Materials (iChEM) State Key Laboratory of Physical Chemistry of Solid Surfaces Department of Chemistry College of Chemistry and Chemical Engineering Xiamen University Xiamen 361005 China.

Sodium metal anodes combine low redox potential (-2.71 V versus SHE) and high theoretical capacity (1165 mAh g), becoming a promising anode material for sodium-ion batteries. Due to the infinite volume change, unstable SEI films, and Na dendrite growth, it is arduous to achieve a long lifespan. Herein, an oxygen-doped carbon foam (OCF) derived from starch is reported. Heteroatom doping can significantly reduce the nucleation resistance of sodium metal; combined with its rich pore structure and large specific surface area, OCF provides abundant nucleation sites to effectively guide the nucleation and subsequent growth of sodium metal, and the nature of this foam can accommodate the deposited sodium. Furthermore, a more uniform, robust, and stable SEI layer is observed on the surface of OCF electrode, so it can maintain ultra-high reversibility and excellent integrity for a long time without dendritic growth. As a result, when the current density is 10 mA cm, the electrode can maintain stable 2000 cycles and the coulombic efficiency can reach to 99.83%. Na@OCF||NaV(PO) full cell also has extremely high capacity retention of about 97.53% over 150 cycles. These results provide a simple but effective method for achieving the safety and commercialization of sodium metal anode.
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http://dx.doi.org/10.1002/advs.202003178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816717PMC
January 2021

Overexpression of HOXA9 upregulates NF-κB signaling to promote human hematopoiesis and alter the hematopoietic differentiation potentials.

Cell Regen 2021 Jan 11;10(1). Epub 2021 Jan 11.

Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Institute of Blood Transfusion, No. 26, Huacai Road, Longtan Industry Park, Chenghua District, Chengdu, 610052, China.

Background: The HOX genes are master regulators of embryogenesis that are also involved in hematopoiesis. HOXA9 belongs to a cluster of HOX genes that play extensively studied roles in hematopoiesis and leukemogenesis.

Methods: We established HOXA9-inducible human embryonic stem cells (HOXA9/hESCs) with normal pluripotency and potential for hematopoiesis, which could be used to analyze gene function with high accuracy. HOXA9/hESCs co-cultured with aorta-gonad-mesonephros-derived stromal cells (AGM-S3) were induced to overexpress HOXA9 with doxycycline (DOX) at various times after hematopoiesis started and then subjected to flow cytometry.

Results: Induction of HOXA9 from Day 4 (D4) or later notably promoted hematopoiesis and also increased the production of CD34+ cells and derived populations. The potential for myelogenesis was significantly elevated while the potential for erythrogenesis was significantly reduced. At D14, a significant promotion of S phase was observed in green fluorescent protein positive (GFP+) cells overexpressing HOXA9. NF-κB signaling was also up-regulated at D14 following induction of HOXA9 on D4. All of these effects could be counteracted by addition of an NF-κB inhibitor or siRNA against NFKB1 along with DOX.

Conclusions: Overexpression of HOXA9 starting at D4 or later during hematopoiesis significantly promoted hematopoiesis and the production of myeloid progenitors while reduced the production of erythroid progenitors, indicating that HOXA9 plays a key role in hematopoiesis and differentiation of hematopoietic lineages.
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http://dx.doi.org/10.1186/s13619-020-00066-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797385PMC
January 2021

Repurposing FDA-Approved Compounds for the Discovery of Glutaminyl Cyclase Inhibitors as Drugs Against Alzheimer's Disease.

ChemistryOpen 2020 Dec 30. Epub 2020 Dec 30.

School of Pharmaceutical Sciences Health Science Center, Shenzhen University, 3688 Nanhai Road, Shenzhen, 518055, China.

Alzheimer's disease (AD) is one of the most common neurodegenerative causes of dementia, the pathology of which is still not much clear. It's challenging to discover the disease modifying agents for the prevention and treatment of AD over the years. Emerging evidence has been accumulated to reveal the crucial role of up-regulated glutaminyl cyclase (QC) in the initiation of AD. In the current study, the QC inhibitory potency of a library consisting of 1621 FDA-approved compounds was assessed. A total of 54 hits, 3.33 % of the pool, exhibited QC inhibitory activities. The Ki of the top 5 compounds with the highest QC inhibitory activities were measured. Among these selected hits, compounds affecting neuronal signaling pathways and other mechanisms were recognized. Moreover, several polyphenol derivatives with QC inhibitory activities were also identified. Frameworks and subsets contained in these hits were analyzed. Taken together, our results may contribute to the discovery and development of novel QC inhibitors as potential anti-AD agents.
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http://dx.doi.org/10.1002/open.202000235DOI Listing
December 2020

Space Optimized Plane Wave Imaging for Fast Ultrasonic Inspection with Small Active Aperture: Simulation and Experiment.

Sensors (Basel) 2020 Dec 24;21(1). Epub 2020 Dec 24.

School of Physical Science and Technology, Southwest Jiaotong University, Chengdu 610031, China.

Plane wave imaging (PWI) is attracting more attention in industrial nondestructive testing and evaluation (NDT&E). To further improve imaging quality and reduce reconstruction time in ultrasonic imaging with a limited active aperture, an optimized PWI algorithm was proposed for rapid ultrasonic inspection, with the comparison of the total focusing method (TFM). The effective area of plane waves and the space weighting factor were defined in order to balance the amplitude of the imaging area. Experiments were carried out to contrast the image quality, with great agreement to the simulation results. Compared with TFM imaging, the space-optimized PWI algorithm demonstrated a wider dynamic detection range and a higher defects amplitude, where the maximum defect amplitude attenuation declined by 6.7 dB and average attenuation on 12 defects decreased by 3.1 dB. In addition, the effects of plane wave numbers on attenuation and reconstruction time were focused on, achieving more than 10 times reduction of reconstruction times over TFM.
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http://dx.doi.org/10.3390/s21010055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795535PMC
December 2020

Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway.

Bioengineered 2021 Dec;12(1):402-413

Urology Surgery Department, The Second Affiliated Hospital of Chongqing Medical University , Chongqing, China.

In this study, we examined the antitumor effects of Puerarin (PEU) on androgen-independent (DU145 and PC-3) and androgen-dependent (LNCaP) prostate cancer cells, and explored its potential mechanisms. Supplement with PEU (2.5 μM, 5 μM, and 10 μM) exhibited a marked inhibitory effect against the growth of DU145 and PC-3 cells, especially beyond 24 h, whereas there is only slight growth inhibitory effect on LNCaP cells at the high concentration of 10 μM at 72 h. This loss of cell viability in DU145 and PC-3 cells by PEU was mediated by the induction of apoptosis via up-regulation of Bax and cleaved-caspase-3, but downregulation of Bcl-2. Moreover, more intracellular ROS and LDH production were observed in DU145 and PC-3 cells upon PEU treatment. Meanwhile, the amount of pro-inflammatory cytokines (IL-1β and IL-6) was increased, but the content of anti-inflammatory cytokines IL-10 was attenuated. Additionally, PEU pretreatment resulted in an increase of Keap1 protein expression, and a decline of Nrf2, HO-1 and NQO1 protein expression in DU145 and PC3 cells. The present findings indicated that PEU exerted its antitumor activities toward androgen-independent prostate cancer cells via inactivation of Keap1/NrF2/ARE signaling pathway.
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http://dx.doi.org/10.1080/21655979.2020.1868733DOI Listing
December 2021

Isoflurane reduces septic neuron injury by HO‑1‑mediated abatement of inflammation and apoptosis.

Mol Med Rep 2021 Feb 23;23(2). Epub 2020 Dec 23.

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

Sepsis‑associated encephalopathy (SAE) frequently occurs in critically ill patients with severe systemic infections. Subanesthetic isoflurane (0.7% ISO) possesses anti‑inflammatory, antioxidant and anti‑apoptotic properties against a number of human diseases, including brain injury. The activation of heme oxygenase‑1 (HO‑1) impedes inflammation, oxidation and apoptosis, thus alleviating sepsis‑induced brain damage. However, whether 0.7% ISO affords protection against septic neuronal injury involving HO‑1 activation is unclear. The present study aimed to investigate the neuroprotective effects of 0.7% ISO and its potential underlying mechanisms in SAE using a mouse model established by cecal ligation and puncture (CLP). The results indicated that the expression and activity of HO‑1 in the mouse hippocampus were increased by CLP, and further enhanced by ISO. ISO reduced the death rate, brain water content and blood‑brain barrier disruption, but improved the learning and memory functions of CLP‑treated mice. ISO significantly decreased the production of pro‑inflammatory cytokines and the levels of oxidative indictors in the serum and hippocampus, as well as the number of apoptotic neurons and the expression of pro‑apoptotic proteins in the hippocampus. Inversely, anti‑inflammatory factors, antioxidative enzymes and anti‑apoptotic proteins were markedly increased by ISO administration. However, the neuroprotective effects of ISO were abolished by a HO‑1 inhibitor. Overall, these findings suggested that 0.7% ISO alleviated SAE via its anti‑inflammatory, antioxidative and anti‑apoptotic properties, which involved the activated form of HO‑1.
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http://dx.doi.org/10.3892/mmr.2020.11794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789092PMC
February 2021

Water content as a primary parameter determines microbial reductive dechlorination activities in soil.

Chemosphere 2021 Mar 1;267:129152. Epub 2020 Dec 1.

Environmental Microbiomics Research Center, School of Environmental Science and Engineering, Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-Sen University, Guangzhou, 510006, China. Electronic address:

Organohalide-respiring bacteria (OHRB) remove halogens from a variety of organohalides, which have been utilized for in situ remediation of different contaminated sites, e.g., groundwater, sediment and soil. Nonetheless, dehalogenation activities of OHRB and consequent remediation efficiencies can be synergistically affected by water content, soil type and inoculated/indigenous OHRB, which need to be disentangled to identify the key driving parameter and to elucidate the underlying mechanism. In this study, we investigated the impacts of water content (0-100%), soil type (laterite, brown soil and black soil) and inoculated OHRB (Dehalococcoides mccartyi CG1 and a river sediment culture) on reductive dechlorination of perchloroethene (PCE) and polychlorinated biphenyls (PCBs), as well as on associated microbial communities. Results suggested that the water content as a primary rate-limiting parameter governed dechlorination activities in environmental matrices, particularly in the soil, possibly through mediation of cell-to-organohalide mobility of OHRB. By contrast, interestingly, organohalide-dechlorinating microbial communities were predominantly clustered based on soil types, rather than water contents or inoculated OHRB. This study provided knowledge on the impacts of major parameters on OHRB-mediated reductive dechlorination in groundwater, sediment and soil for future optimization of in situ bioremediation of organohalides.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129152DOI Listing
March 2021

Highly Stable Low-Cost Electrochemical Gas Sensor with an Alcohol-Tolerant N,S-Codoped Non-Precious Metal Catalyst Air Cathode.

ACS Sens 2021 03 11;6(3):752-763. Epub 2020 Dec 11.

Department of Chemical Engineering, Waterloo Institute for Nanotechnology, Waterloo Institute for Sustainable Energy, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

The emerging applications of electrochemical gas sensors (EGSs) in Internet of Things-enabled smart city and personal health electronics bring out a new challenge for common EGSs, such as alcohol fuel cell sensors (AFCSs) to reduce the dependence on a pricy Pt catalyst. Here, for the first time, we propose a low-cost novel N,S-codoped metal catalyst (FeNSC) to accelerate oxygen reduction reaction (ORR) and replace the Pt catalyst in the cathode of an AFCS. The optimal FeNSC shows high ORR activity, stability, and alcohol tolerance. Furthermore, the FeNSC-based AFCS not only demonstrates excellent linearity, low detection limit, high stability, and superior sensitivity to that of the commercial Pt/C-based AFCS but also outperforms commercial Pt/C-based AFCS in the exposed cell regarding great linearity, high sensitivity, and great stability. Such a promising sensor performance not just proves the concept of the FeNSC-based ACFS but enlightens the next-generation designs toward low-cost, highly sensitive, and durable EGSs.
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http://dx.doi.org/10.1021/acssensors.0c01466DOI Listing
March 2021

Identification and Validation of New Stable QTLs for Grain Weight and Size by Multiple Mapping Models in Common Wheat.

Front Genet 2020 11;11:584859. Epub 2020 Nov 11.

KeyLaboratory of Wheat Biology and Genetic Improvement on Southern Yellow and Huai River Valley, Ministry of Agriculture and Rural Affairs, College of Agronomy, Anhui Agricultural University, Hefei, China.

Improvement of grain weight and size is an important objective for high-yield wheat breeding. In this study, 174 recombinant inbred lines (RILs) derived from the cross between Jing 411 and Hongmangchun 21 were used to construct a high-density genetic map by specific locus amplified fragment sequencing (SLAF-seq). Three mapping methods, including inclusive composite interval mapping (ICIM), genome-wide composite interval mapping (GCIM), and a mixed linear model performed with forward-backward stepwise (NWIM), were used to identify QTLs for thousand grain weight (TGW), grain width (GW), and grain length (GL). In total, we identified 30, 15, and 18 putative QTLs for TGW, GW, and GL that explain 1.1-33.9%, 3.1%-34.2%, and 1.7%-22.8% of the phenotypic variances, respectively. Among these, 19 (63.3%) QTLs for TGW, 10 (66.7%) for GW, and 7 (38.9%) for GL were consistent with those identified by genome-wide association analysis in 192 wheat varieties. Five new stable QTLs, including 3 for TGW (, , and ) and 2 for GL ( and ), were detected by the three aforementioned mapping methods across environments. Subsequently, five cleaved amplified polymorphic sequence (CAPS) markers corresponding to these QTLs were developed and validated in 180 Chinese mini-core wheat accessions. In addition, 19 potential candidate genes for in a 0.31-Mb physical interval were further annotated, of which and encode a plasma membrane H-ATPase and a serine/threonine-protein kinase, respectively. These new QTLs and CAPS markers will be useful for further marker-assisted selection and map-based cloning of target genes.
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http://dx.doi.org/10.3389/fgene.2020.584859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686802PMC
November 2020

The Role of Brown Adipose Tissue in the Development and Treatment of Nonalcoholic Steatohepatitis: An Exploratory Gene Expression Study in Mice.

Horm Metab Res 2020 Dec 1;52(12):869-876. Epub 2020 Dec 1.

Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium.

Brown adipose tissue (BAT) might be a beneficial mediator in the development and treatment of nonalcoholic steatohepatitis (NASH). We aim to evaluate the gene expression of BAT activity-related genes during the development and the dietary and surgical treatment of NASH. BAT was collected from male mice that received a high fat-high sucrose diet (HF-HSD) or a normal chow diet (NCD) for 4 and 20 weeks (n=8-9 per dietary group and timepoint) and from mice that underwent dietary intervention (return to NCD) (n=8), roux-en-y gastric bypass (RYGB) (n=6), or sham procedure (n=6) after 12 weeks HF-HSD. Expression of BAT genes involved in lipid metabolism (Cd36 and Cpt1b; p<0.05) and energy expenditure (Ucp1 and Ucp3; p<0.05) were significantly increased after 4 weeks HF-HSD compared with NCD, whereas in the occurrence of NASH after 20 weeks HF-HSD no difference was observed. We observed no differences in gene expression regarding lipid metabolism or energy expenditure at 8 weeks after dietary intervention (no NASH) compared with HF-HSD mice (NASH), nor in mice that underwent RYGB compared with SHAM. However, dietary intervention and RYGB both decreased the BAT gene expression of inflammatory cytokines (Il1b, Tnf-α and MCP-1; p<0.05). Gene expression of the neuregulin 4 was significantly decreased after 20 weeks HF-HSD (p<0.05) compared with NCD, but was restored by dietary intervention and RYGB (p<0.05). In conclusion, BAT is hallmarked by dynamic alterations in the gene expression profile during the development of NASH and can be modulated by dietary intervention and bariatric surgery.
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http://dx.doi.org/10.1055/a-1301-2378DOI Listing
December 2020

Enantioselective Intermolecular Radical C-H Amination.

J Am Chem Soc 2020 12 25;142(49):20828-20836. Epub 2020 Nov 25.

Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, United States.

Radical reactions hold a number of inherent advantages in organic synthesis that may potentially impact the planning and practice for construction of organic molecules. However, the control of enantioselectivity in radical processes remains one of the longstanding challenges. While significant advances have recently been achieved in intramolecular radical reactions, the governing of asymmetric induction in intermolecular radical reactions still poses challenging issues. We herein report a catalytic approach that is highly effective for controlling enantioselectivity as well as reactivity of the intermolecular radical C-H amination of carboxylic acid esters with organic azides via Co(II)-based metalloradical catalysis (MRC). The key to the success lies in the catalyst development to maximize noncovalent attractive interactions through fine-tuning of the remote substituents of the -symmetric chiral amidoporphyrin ligand. This noncovalent interaction strategy presents a solution that may be generally applicable in controlling reactivity and enantioselectivity in intermolecular radical reactions. The Co(II)-catalyzed intermolecular C-H amination, which operates under mild conditions with the C-H substrate as the limiting reagent, exhibits a broad substrate scope with high chemoselectivity, providing effective access to valuable chiral amino acid derivatives with high enantioselectivities. Systematic mechanistic studies shed light into the working details of the underlying stepwise radical pathway for the Co(II)-based C-H amination.
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http://dx.doi.org/10.1021/jacs.0c10415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726091PMC
December 2020

Sunitinib malate inhibits intestinal tumor development in male Apc mice by down-regulating inflammation-related factors with suppressing β-cateinin/c-Myc pathway and re-balancing Bcl-6 and Caspase-3.

Int Immunopharmacol 2021 Jan 13;90:107128. Epub 2020 Nov 13.

Laboratory Animal Research Center for Science and Technology, Jiangxi University of Traditional Chinese Medicine, 1688 Meiling Road, Nanchang 330004, China; Key Laboratory of Pharmacology of Traditional Chinese Medicine in Jiangxi, Nanchang 330004, China; Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China. Electronic address:

Sunitinib is a tyrosine kinase inhibitor for many tumors. Inflammation is one of the most important factors in the development of intestinal tumors. Many inflammation-related factors are regulated by tyrosine kinase receptors. It is reasonable to hypothesize that sunitinib can regulate the development of intestinal tumors by regulating the expression and/or activity of inflammation-related factors. Here, Apc male mouse model was used to investigate the effect and mechanism of sunitinib malate against intestinal cancer. Results show that compared to vehicle, after sunitinib malate treatment, overall survival of Apc mice was lengthened up to 25 days, with a gain of body weight, reduction of spleen/body weight index, and RBC, WBC and HGC regulated to normal levels of wild type mice, and a number of polyps no less than 1 mm significantly reduced. Meanwhile, in the intestines, the nuclear β-Catenin protein and c-Myc mRNA were both down-regulated, and Bcl-6 was significantly reduced with Caspase-3 up regulated. Furthermore, inflammation-related factors including IL-6, TNF-α, IL-1α, IL-1β and IFN-γ were down-regulated at mRNA levels in the intestines. These results suggest that sunitinib malate can significantly improve the survival status and inhibit intestinal tumor development in male Apc mice, through inhibiting inflammation-related factors, while suppressing β-cateinin/c-Myc pathway and re-balancing protein levels of Bcl-6 and Caspase-3.
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http://dx.doi.org/10.1016/j.intimp.2020.107128DOI Listing
January 2021

Engeletin ameliorates pulmonary fibrosis through endoplasmic reticulum stress depending on lnc949-mediated TGF-β1-Smad2/3 and JNK signalling pathways.

Pharm Biol 2020 Dec;58(1):1105-1114

Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.

Context: Pulmonary fibrosis (PF) is a highly heterogeneous and lethal pathological process having no effective drug. Engeletin exerts multiple biological activities including anti-inflammatory and lung repair. Whether engeletin has therapeutic effects on PF remains unclear.

Objective: Examining effect and mechanism of engeletin on PF and

Materials And Methods: L929 cells (1 × 10/well) were treated with TGF-β1 (5 ng/mL). Sixty male C57BL/6 mice were divided into three groups and given saline or single intratracheal instillation bleomycin (5 mg/kg) or both bleomycin and intraperitoneally injected engeletin (25 mg/kg).

Results: Histological staining showed engeletin inhibited myofibrobasts activation and improved alveolar structure. Engeletin elevated forced vital capacity from 12 induced by bleomycin to 17. CCK-8 assay reported IC value of engeletin was 270 μg/mL. Real-time cellular analysis showed engeletin reduced proliferation and migration of myofibroblasts by 2.5- and 2-fold. Engeletin blocked α-SMA, vimentin, and collagen expression. RNA sequencing revealed PERK-ATF4 signalling pathway relating to ER stress involved in anti-fibrotic function of engeletin. Engeletin reduced ATF4, CHOP and BIP expression. Chemical inhibitors of smad2/3- (SB431542) and JNK- (SP600125) signalling pathways blocked expression of long noncoding RNA (lncRNA) - lnc949. Engeletin inhibited phosphorylation of smad2/3 and JNK leading to lower level of lnc949. Knockdown lnc949 inhibited ATF4, CHOP and BIP expression.

Conclusions: We reported gene expression profiling of engeletin through RNA-seq; and identified lnc949-mediated TGF-β1-Smad2/3 and JNK were upstream signalling pathways of ER stress induced by engeletin. Our results showed engeletin remedies pulmonary fibrogenesis and may be a new drug candidate.
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http://dx.doi.org/10.1080/13880209.2020.1834590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671710PMC
December 2020

COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support.

medRxiv 2020 Nov 5. Epub 2020 Nov 5.

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.
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http://dx.doi.org/10.1101/2020.11.03.20225409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654910PMC
November 2020