Publications by authors named "Jun Yu"

1,640 Publications

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Integrative metabolomic characterisation identifies altered portal vein serum metabolome contributing to human hepatocellular carcinoma.

Gut 2021 Aug 3. Epub 2021 Aug 3.

Institute of Digestive Disease and The Department of Medicine and Therapeutics,State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences,CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China SAR

Objective: Altered metabolites are important for the tumourigenicity of hepatocellular carcinoma (HCC). We performed integrative metabolomics analysis of the metabolites changes in portal venous blood and in comparison with the metabolites changes in liver tissues and stool samples of HCC patients and healthy liver donors.

Design: Serum (portal and central vein), liver tissue (HCC tumour and adjacent non-tumour, normal liver) and stool samples were collected from 102 subjects (52 HCC patients and 50 healthy controls) in the discovery cohort; and 100 subjects (50 HCC patients and 50 healthy controls) in an independent validation cohort. Untargeted metabolomic profiling was performed using high-performance liquid chromatography-mass spectrometry. The function of candidate metabolites was validated in hepatocyte cell lines.

Results: Detailed metabolomic evaluation showed distinct clusters of metabolites in serum, liver tissue and stool samples from patients with HCC and control individuals (p<0.001). HCC patients had significantly higher levels of portal vein serum and HCC tissue metabolites of DL-3-phenyllactic acid, L-tryptophan, glycocholic acid and 1-methylnicotinamide than healthy controls, which were associated with impaired liver function and poor survival. On the other hand, HCC patients had lower levels of linoleic acid and phenol in portal vein and stool samples than healthy controls. Linoleic acid and phenol significantly inhibited HCC proliferation, inferring their anti-HCC function as protective metabolites.

Conclusions: The integrative metabolome analysis of serum, tissue and stool metabolites revealed unreported metabolic alterations in HCC patients. In portal vein, we identified elevated and depleted metabolites signifying that they might play a role in HCC development.
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http://dx.doi.org/10.1136/gutjnl-2021-325189DOI Listing
August 2021

Interleukin-10 levels and risk of gestational diabetes mellitus: a systematic review and meta-analysis.

J Matern Fetal Neonatal Med 2021 Aug 4:1-8. Epub 2021 Aug 4.

Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background And Objective: Association of interleukin-10 (IL-10) polymorphism with diabetes and its complication was recently established, while there were few kinds of research considering the potential role of IL-10 in gestational diabetes (GDM). This study aimed to systematically review the association between serum IL-10 level and GDM susceptibility.

Methods: A comprehensive literature search for the published studies in PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), and Google Scholar databases was performed for English language papers published up to 31st July 2020. Following key terms were used: "Cytokine level" OR "Interleukin-10" OR "IL-10," OR "Pro-inflammatory Cytokines" OR "gestational diabetes mellitus" OR "GDM." Fixed or random-effects models were used to estimate the pooled SDM and 95% confidence intervals (CIs). Begg's funnel plot was used to assess the potential for publication bias.

Results: In our meta-analysis, a total of ten studies for risk of GDM involving 609 GDM cases and 664 controls were included. No significant association between IL-10 levels and risk of GDM as compared to control subjects (SMD = -0.09, 95% CI = -0.73 to 0.55). Subgroup analysis based on ethnicity also does not reveal any association between IL-10 levels and risk of GDM as compared to control subjects has more or less similar trends in Caucasian (SMD = -0.07, 95% CI = -0.58 to 0.45) as well as Asian population (SMD = -0.03, 95% CI = -1.56 to 1.49).

Conclusion: Our findings suggest that the serum IL-10 level may not be significantly associated with an increased risk of susceptibility to GDM. Further well-designed prospective studies embedded with a large sample size are needed to confirm these findings.
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http://dx.doi.org/10.1080/14767058.2021.1957820DOI Listing
August 2021

SARS-CoV-2 activates lung epithelial cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients.

EBioMedicine 2021 Jul 23;70:103500. Epub 2021 Jul 23.

Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.

Background: The outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global health emergency. We aim to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in lung of COVID-19 patients.

Methods: We analyzed single-cell RNA sequencing (scRNA-seq) data of bronchoalveolar lavage fluid (BALF) samples from 10 healthy donors, 6 severe COVID-19 patients and 3 mild recovered patients. The expressions of SARS-CoV-2 receptors (ACE2 and TMPRSS2) were examined among different cell types. The immune cells infiltration patterns, their expression profiles, and interplays between immune cells and SARS-CoV-2 target cells were further investigated.

Findings: Compared to healthy controls, ACE2 and TMPRSS2 expressions were significantly higher in lung epithelial cells of COVID-19 patients, in particular club and ciliated cells. SARS-CoV-2 activated pro-inflammatory genes and interferon/cytokine signaling in these cells. In severe COVID-19 patients, significantly higher neutrophil, but lower macrophage in lung was observed along with markedly increased cytokines expression compared with healthy controls and mild patients. By contrast, neutrophil and macrophage returned to normal level whilst more T and NK cells accumulation were observed in mild patients. Moreover, SARS-CoV-2 infection altered the community interplays of lung epithelial and immune cells: interactions between the club and immune cells were higher in COVID-19 patients compared to healthy donors; on the other hand, immune-immune cells interactions appeared the strongest in mild patients.

Interpretation: SARS-CoV-2 could infect lung epithelium, alter communication patterns between lung epithelial cells and immune system, and drive dysregulated host immune response in COVID-19 patients.
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http://dx.doi.org/10.1016/j.ebiom.2021.103500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302220PMC
July 2021

Structural basis of human separase regulation by securin and CDK1-cyclin B1.

Nature 2021 Jul 21. Epub 2021 Jul 21.

Department of Molecular Biology, University of Geneva, Geneva, Switzerland.

In early mitosis, the duplicated chromosomes are held together by the ring-shaped cohesin complex. Separation of chromosomes during anaphase is triggered by separase-a large cysteine endopeptidase that cleaves the cohesin subunit SCC1 (also known as RAD21). Separase is activated by degradation of its inhibitors, securin and cyclin B, but the molecular mechanisms of separase regulation are not clear. Here we used cryogenic electron microscopy to determine the structures of human separase in complex with either securin or CDK1-cyclin B1-CKS1. In both complexes, separase is inhibited by pseudosubstrate motifs that block substrate binding at the catalytic site and at nearby docking sites. As in Caenorhabditis elegans and yeast, human securin contains its own pseudosubstrate motifs. By contrast, CDK1-cyclin B1 inhibits separase by deploying pseudosubstrate motifs from intrinsically disordered loops in separase itself. One autoinhibitory loop is oriented by CDK1-cyclin B1 to block the catalytic sites of both separase and CDK1. Another autoinhibitory loop blocks substrate docking in a cleft adjacent to the separase catalytic site. A third separase loop contains a phosphoserine that promotes complex assembly by binding to a conserved phosphate-binding pocket in cyclin B1. Our study reveals the diverse array of mechanisms by which securin and CDK1-cyclin B1 bind and inhibit separase, providing the molecular basis for the robust control of chromosome segregation.
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http://dx.doi.org/10.1038/s41586-021-03764-0DOI Listing
July 2021

Reliable Detection of Somatic Mutations for Pancreatic Cancer in Endoscopic Ultrasonography-Guided Fine Needle Aspirates with Next-Generation Sequencing: Implications from a Prospective Cohort Study.

J Gastrointest Surg 2021 Jul 9. Epub 2021 Jul 9.

Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.

Background Or Purpose: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). However, the diagnostic adequacy of EUS-FNA is often limited by low cellularity leading to inconclusive results. We aimed to investigate the feasibility and added utility of targeted next-generation sequencing (NGS) on PDAC EUS-FNAs.

Methods: EUS-FNAs were prospectively performed on 59 patients with suspected PDAC (2014-2017) at a high-volume center. FNAs were analyzed for the presence of somatic mutations using NGS to supplement cytopathologic evaluations and were compared to surgical specimens and circulating tumor DNA (ctDNA).

Results: Fifty-nine patients with suspected PDAC were evaluated, and 52 were diagnosed with PDAC on EUS-FNA. Four of the remaining seven patients had inconclusive EUS-FNAs and were ultimately diagnosed with PDAC after surgical resection. Of these 56 cases of PDAC, 48 (85.7%) and 18 (32.1%) harbored a KRAS and/or TP53 mutation on FNA NGS, respectively. Particularly, in the four inconclusive FNA PDAC diagnoses (false negatives), half harbored KRAS mutations on FNA. No KRAS/TP53 mutation was found in remaining three non-PDAC cases. All EUS-FNA detected KRAS mutations were detected in 16 patients that underwent primary tumor NGS (100% concordance), while 75% KRAS concordance was found between FNA and ctDNA NGS.

Conclusion: Targeted NGS can reliably detect KRAS mutations from EUS-FNA samples and exhibits high KRAS mutational concordance with primary tumor and ctDNA. This suggests targeted NGS of EUS-FNA samples may enable preoperative ctDNA prognostication using digital droplet PCR and supplement diagnoses in patients with inconclusive EUS-FNA.
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http://dx.doi.org/10.1007/s11605-021-05078-yDOI Listing
July 2021

Ovarian Metastasis from Pancreatic Ductal Adenocarcinoma.

World J Surg 2021 Jul 8. Epub 2021 Jul 8.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a high propensity for systemic dissemination. Ovarian metastases are rare and poorly described.

Methods: We identified PDAC cases with ovarian metastasis from a prospectively maintained registry. We reported on the association between outcomes and clinicopathologic factors. Recurrence-free (RFS) and overall survival (OS) were calculated using Kaplan-Meier analysis.

Results: Twelve patients with PDAC and synchronous or metachronous ovarian metastases were identified. Nine patients (75%) underwent pancreatectomy for localized PDAC and developed metachronous ovarian recurrence. The median OS for all patients was 25.4 (IQR:15.4-82.9) months. For the nine patients with metachronous ovarian metastasis, the median RFS and OS were 14.2 (IQR:7.2-58.3) and 44.6 (IQR:18.6-82.9) months, respectively. Nodal disease, poor grade, vascular invasion in the pancreatic primary, and bilateral ovarian disease tended to confer worse outcomes.

Conclusion: Patients with resected PDAC and ovarian recurrence tend to have a comparable disease course to more common patterns of recurrence. Primaries with nodal disease, poorer grade, vascular invasion, and bilateral ovarian disease were indicative of more aggressive disease biology. The ideal management remains largely unknown, and future collaborative efforts should optimize therapeutic strategies.
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http://dx.doi.org/10.1007/s00268-021-06209-xDOI Listing
July 2021

Lymph Node Metastatic Patterns and Survival Predictors Based on Tumor Size in Pancreatic Ductal Adenocarcinoma.

Adv Ther 2021 Jun 26. Epub 2021 Jun 26.

Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Larger tumor size is widely acknowledged to be associated with increased lymph node (LN) metastatic potential. However, the quantitative relationships between tumor size and LN metastasis or survival remain unclear. This study aims to quantify the objective relationship between tumor size and the prevalence of LN metastases across a spectrum primary tumor size.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 9958 patients with resected PDAC without distant metastasis. The prevalence of LN metastases, LN ratio (LNR), and N2/N1 ratio were assessed amongst different tumor sizes, and the relationships were displayed by matched curves.

Results: In the enrolled cohort, age, tumor site, grade, American Joint Committee on Cancer (AJCC) 8th node staging, tumor size, chemotherapy, and radiotherapy were identified as significant independent predictors for overall survival (OS) and cancer-specific survival (CSS). For tumors within 1-40 mm in size, the prevalence of node-positive disease is closely modelled using a logarithmic formula [0.249 × ln (size) + 0.452] × 100%. The prevalence plateaued between 70% and 80% beyond 40 mm. The mean LNR increased in a stepwise manner as tumor size increased from 1-5 mm (LNR = 0.024) to 41-45 mm (LNR = 0.177); then, beyond 45 mm, it plateaued near 0.170. N2/N1 ratio gradually increased along with tumor size from 1-5 mm (N2/N1 = 0.286) to 41-45 mm (N2/N1 = 1.016), and when tumor size reached to 41-45 mm or more, the ratio stabilized around 1.000. In addition, significant survival prediction by AJCC N staging was observed when tumors ranging between 16 and 45 mm in size.

Conclusion: Regional LN involvement demonstrated a logarithmic growth with increasing tumor sizes in patients with resected PDAC . The probability of metastasis in each regional LN for resected PDAC with tumors greater than 40 mm in size was near 17.0% and their overall prevalence of LN metastasis was 70-80%. Among which, 50% of patients had an N2 stage. Such prediction may be a potential and promising tool for guiding lymphadenectomy in PDAC surgery.
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http://dx.doi.org/10.1007/s12325-021-01819-2DOI Listing
June 2021

J Pharmacol Exp Ther 2021 Jun 22. Epub 2021 Jun 22.

Center for Metabolic Disease Research and Department of Physiology, Lewis Katz School of Medicine, Temple University, United States.

The (pro)renin receptor (PRR) is a single-transmembrane protein that regulates the local renin-angiotensin system and participates in various intracellular signaling pathways, thus exhibiting a significant physio-pathological relevance in cellular homeostasis. A soluble form of PRR (sPRR) is generated through proteases-mediated cleavage of the full-length PRR and secreted into extracellular spaces. Accumulating evidence indicates pivotal biological functions of sPRR in various physiopathological processes. sPRR may be a novel biomarker for multiple diseases. Circulating sPRR concentrations are elevated in patients and animals under various physiopathological conditions. Here we highlight recent advances in sPRR functions in health and pathophysiological conditions. Results suggest that sPRR may be a novel biomarker for multiple diseases, but further studies are needed to determine the diagnostic value of sPRR.
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http://dx.doi.org/10.1124/jpet.121.000576DOI Listing
June 2021

Self-efficacy as a crucial psychological predictor of treatment adherence among elderly people living with HIV: analyses based on the health belief model.

AIDS Care 2021 Jun 22:1-7. Epub 2021 Jun 22.

Department of Health Related Social and Behavioral Science, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, People's Republic of China.

Medication adherence to antiretroviral therapy (ART) among elderly people living with HIV (PLWH) is of serious concern. Our study aimed to understand the medication adherence of elderly PLWH under ART based on the health belief model (HBM). A baseline survey with a total of 529 elderly PLWH was conducted in Sichuan. Logistic and linear regression analysis, mediation analysis, and path analysis based on prior evidence were used. Only self-efficacy showed direct associations with medication adherence in the last four days (ORm = 1.37, 95%CI: 1.11, 1.70) and the last month (ORm = 1.39, 95%CI: 1.18, 1.63) in the multivariate analysis. Self-efficacy mediated the relations between perceived benefits, perceived barriers, cues to action and medication adherence. Inner relations existed within the HBM. In addition to the direct effects, perceived benefits (β = 0.149,  = 0.031; β = 0.093,  = 0.005), perceived barriers (β = -0.070,  = 0.008; β = -0.062,  = 0.012), and cues to action (β = 0.184,  = 0.013; β = 0.135,  = 0.014) showed indirect effects on medication adherence in the last four days and the last month, respectively. HBM may be effective in predicting medication adherence of elderly PLWH, and self-efficacy may be a crucial predictor and mediator. Efforts should be focused on how to enhance elderly PLWH's self-efficacy without neglect of other medication beliefs.
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http://dx.doi.org/10.1080/09540121.2021.1938964DOI Listing
June 2021

Gut lactate-producing bacteria promote CD4 T cell recovery on Anti-retroviral therapy in HIV-infected patients.

Comput Struct Biotechnol J 2021 11;19:2928-2937. Epub 2021 May 11.

CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, & China National Center for Bioinformation, Beijing 100101, China.

Anti-retroviral therapy (ART) effectively suppresses viral replication in HIV-infected patients, however CD4 + cell restoration to normal value is not achieved by 15-20% of patients who are called immune non-responders. Gut microbiota composition has been shown to influence host immunity. Herein, to identify intestinal microbial agents that may influence the CD4 recovery in HIV-infected patients, we utilized a "Quasi-paired cohort" method to analyze intestinal metagenome data from immunological responders (IRs) and immunological non-responders (INRs). This method identified significant enrichment for sp. and related lactate-producing bacteria (LAB) in IRs. In a validation cohort, positive correlations between the abundance of these LAB and the post-ART CD4 + recovery was observed, and a prediction model based on these LAB performed well in predicting immune recovery. Finally, experiments using a germ-free mouse model of antibody-induced CD4 + cell depletion showed that supplementation with a lactate-producing commensal strongly promoted CD4 recovery. In conclusion, our study identified a group of LAB that was associated with enhanced immune recovery in post-ART HIV-infected patients and promotes CD4 + cell restoration in a mouse model. These findings favour supplementation of LAB commensal as a therapeutic strategy for CD4 + cell count improvement in HIV-infected patients.
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http://dx.doi.org/10.1016/j.csbj.2021.05.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191414PMC
May 2021

Targeting the αv integrin/TGF-β axis improves natural killer cell function against glioblastoma stem cells.

J Clin Invest 2021 Jul;131(14)

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Glioblastoma multiforme (GBM), the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, are sensitive to lysis by healthy allogeneic natural killer (NK) cells in vitro. Mass cytometry and single-cell RNA sequencing of primary tumor samples revealed that GBM tumor-infiltrating NK cells acquired an altered phenotype associated with impaired lytic function relative to matched peripheral blood NK cells from patients with GBM or healthy donors. We attributed this immune evasion tactic to direct cell-to-cell contact between GSCs and NK cells via αv integrin-mediated TGF-β activation. Treatment of GSC-engrafted mice with allogeneic NK cells in combination with inhibitors of integrin or TGF-β signaling or with TGFBR2 gene-edited allogeneic NK cells prevented GSC-induced NK cell dysfunction and tumor growth. These findings reveal an important mechanism of NK cell immune evasion by GSCs and suggest the αv integrin/TGF-β axis as a potentially useful therapeutic target in GBM.
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http://dx.doi.org/10.1172/JCI142116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279586PMC
July 2021

mA Modification in Mammalian Nervous System Development, Functions, Disorders, and Injuries.

Front Cell Dev Biol 2021 25;9:679662. Epub 2021 May 25.

Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Brain Research Center, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.

-methyladenosine (mA) modification, as the most prevalent internal modification on mRNA, has been implicated in many biological processes through regulating mRNA metabolism. Given that mA modification is highly enriched in the mammalian brain, this dynamic modification provides a crucial new layer of epitranscriptomic regulation of the nervous system. Here, in this review, we summarize the recent progress on studies of mA modification in the mammalian nervous system ranging from neuronal development to basic and advanced brain functions. We also highlight the detailed underlying mechanisms in each process mediated by mA writers, erasers, and readers. Besides, the involvement of dysregulated mA modification in neurological disorders and injuries is discussed as well.
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http://dx.doi.org/10.3389/fcell.2021.679662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185210PMC
May 2021

The paradox of immunotherapy in NASH-HCC.

Signal Transduct Target Ther 2021 Jun 10;6(1):228. Epub 2021 Jun 10.

Department of Gastroenterology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.

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http://dx.doi.org/10.1038/s41392-021-00654-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192918PMC
June 2021

Local administration of liposomal-based Srpx2 gene therapy reverses pulmonary fibrosis by blockading fibroblast-to-myofibroblast transition.

Theranostics 2021 13;11(14):7110-7125. Epub 2021 May 13.

Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of National Health Commission, Key Site of National Clinical Research Center for Respiratory Disease, Wuhan Clinical Medical Research Center for Chronic Airway Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, 1095 Jiefang Ave, Wuhan 430030, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fatal interstitial lung disease characterized by abnormal transition and proliferation of fibroblasts. The uncontrolled transition of fibroblasts, commonly known as myofibroblasts, are the principal source of the enormous extracellular matrix (ECM) depositing in lung parenchyma, leading to gradual failure of gas exchange and mortality of the patients. However, up to now, rare effective therapeutic strategies have been developed to blockade fibroblast-to-myofibroblast transition (FMT) in IPF. We illustrated that the lungs originated from IPF patients and mice with pulmonary fibrosis are characterized by the overexpression of sushi-repeat-containing protein, X-linked 2 (SRPX2). Further functionality studies identified the pivotal role of SRPX2 in FMT. Mechanistically, SRPX2 was involved in a TGFβR1/SMAD3/SRPX2/AP1/SMAD7 positive feedback loop. Specifically, SRPX2 was upregulated by TGF-β1 in a TGFβR1/SMAD3-dependent manner, after which SRPX2 in turn repressed the expression of AP1, subsequently minimized SMAD7 expression, through which it reduced the formation of inhibitory complex with TGFβR1 and enhanced SMAD signaling pathway to promote FMT and exacerbate pulmonary fibrosis. Notably, intratracheal administration of siRNA-loaded liposomes could effectively suppress the expression of Srpx2 in the lung and remarkably protect mice against BLM-induced pulmonary fibrosis, concomitant with a significant reduction of FMT. Accordingly, these data indicate that Srpx2 plays an essential role in the pathogenesis of pulmonary fibrosis and suggests the strategy aiming at silencing Srpx2 could be a promising therapeutic approach against pulmonary fibrosis in clinical settings.
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http://dx.doi.org/10.7150/thno.61085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171094PMC
May 2021

Identification of Tumor Necrosis Factor-Alpha (TNF-α) Inhibitor in Rheumatoid Arthritis Using Network Pharmacology and Molecular Docking.

Front Pharmacol 2021 21;12:690118. Epub 2021 May 21.

The Fourth Affiliated Hospital, Anhui Medical University, Hefei, China.

This study aimed to investigate the molecular mechanism of Paeoniae Alba (white peony, WP) in treating immune inflammatory diseases of rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis) by using network pharmacology and molecular docking. In this study, the ingredient of WP and the potential inflammatory targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard, and OMIM databases, respectively. The establishment of the RA-WP-potential inflammatory target gene interaction network was accomplished using the STRING database. Network maps of the WP-RA-potential inflammatory target gene network were constructed using Cytoscape software. Gene ontology (GO) and the biological pathway (KEGG) enrichment analyses were used to further explore the RA mechanism and therapeutic effects of WP. Molecular docking technology was used to analyze the optimal effective components from WP for docking with TNF-α. Thirteen active ingredients and 71 target genes were screened from WP, and 49 of the target genes intersected with RA target inflammatory genes and were considered potential therapeutic targets. Network pharmacological analysis showed that the WP active ingredients such as mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA inflammatory target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, and CHRM2, respectively. The immune-inflammatory signaling pathways of the active ingredients for the treatment of RA are the TNF-α signaling pathway, Toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated protein kinase, . Molecular docking results suggested that mairin was the most appropriate natural TNFis. Our findings provide an essential role and basis for further immune-inflammatory studies into the molecular mechanisms of WP and TNFis development in RA.
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http://dx.doi.org/10.3389/fphar.2021.690118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175775PMC
May 2021

Enhanced Accumulation of Cisplatin in Ovarian Cancer Cells from Combination with Wedelolactone and Resulting Inhibition of Multiple Epigenetic Drivers.

Drug Des Devel Ther 2021 25;15:2211-2227. Epub 2021 May 25.

Eman Research Journal, Eman Research, Sydney, NSW, Australia.

Purpose: Cisplatin resistance is a major concern in ovarian cancer treatment. The aim of this study was to investigate if wedelolactone could perform better in resistant ovarian cancer cells when used in combination with cisplatin.

Methods: Growth inhibitory potential of wedelolactone and cisplatin was investigated through MTT reduction assay in ovarian cancer cell lines including A2780 (sensitive), A2780 (cisplatin resistant) and A2780 Resistance factor (RF) of drugs was determined in these three cell lines. Combination index (CI) was calculated as a measure of combined drug action. Effect of this combination on changes in the cellular accumulation of platinum levels and platinum-DNA binding was also determined using AutoDock Vina while the effect of wedelolactone on inhibition of possible key culprits of resistance including Chk1, CD73, AT tip60, Nrf2, Brd1, PCAF, IGF1, mTOR1 and HIF2α was investigated .

Results: Cisplatin and wedelolactone showed a dose-dependent growth inhibitory effect. RF value of wedelolactone was 1.1 in the case of A2780 showing its potential to bring more cell death in cisplatin-resistant cells. CI values were found to vary showing antagonistic to additive outcomes. Additive effect was observed for all sequences of administration (0/0, 0/4 and 4/0 h) in A2780. Enhanced cellular accumulation of cisplatin was observed in parent and resistant cells on combination. Docking results revealed that among the selected oncotargets, Chk1, CD73, Nrf2, PCAF and AT tip60 were more vulnerable to wedelolactone than their respective standard inhibitors.

Conclusion: These findings have shown that additive outcome of drug combination in A2780 and raised levels of platinum accumulation followed a clear pattern. This observation indicates that the presence of wedelolactone might have contributed to sensitize A2780. However, results point to the possible effects of this compound on epigenetic factors involving tumor microenvironment, epithelial mesenchymal transition, and immune-checkpoint kinases.
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http://dx.doi.org/10.2147/DDDT.S288707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164677PMC
May 2021

Synergistic Effect of Ni/W/Cu on MgAlO for One-Pot Hydrogenolysis of Cellulose to Ethylene Glycol at a Low H Pressure.

ACS Omega 2021 May 20;6(17):11650-11659. Epub 2021 Apr 20.

Guangxi Key Laboratory of Petrochemical Resource Processing and Process Intensification Technology, School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.

Nickel and tungsten, combined with copper, were incorporated into a magnesium aluminum spinel to form a multifunctional catalyst (Ni-W-Cu/MgAlO). Characterization results suggested that the adjacent Cu not only facilitated the reduction of W to W with substantial oxygen vacancies but also promoted the reducibility of the Ni species. Besides, the incorporation of Ni, W, and Cu into the support enhanced the catalytic acidity, as well as the L acid sites. The catalyst exhibited a strong synergistic effect between the three metals and the support, resulting in higher catalytic activity for the one-pot hydrogenolysis of cellulose to ethylene glycol. High cellulose conversion (100%) and ethylene glycol yield (52.8%) were obtained, even under a low H pressure of 3 MPa.
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http://dx.doi.org/10.1021/acsomega.1c00979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153994PMC
May 2021

Local protein synthesis of neuronal MT1-MMP for agrin-induced presynaptic development.

Development 2021 May 20;148(10). Epub 2021 May 20.

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.

Upon the stimulation of extracellular cues, a significant number of proteins are synthesized distally along the axon. Although local protein synthesis is crucial for various stages throughout neuronal development, its involvement in presynaptic differentiation at developing neuromuscular junctions remains unknown. By using axon severing and microfluidic chamber assays, we first showed that treatment of a protein synthesis inhibitor, cycloheximide, inhibits agrin-induced presynaptic differentiation in cultured Xenopus spinal neurons. Newly synthesized proteins are prominently detected, as revealed by the staining of click-reactive cell-permeable puromycin analog O-propargyl-puromycin, at agrin bead-neurite contacts involving the mTOR/4E-BP1 pathway. Next, live-cell time-lapse imaging demonstrated the local capturing and immobilization of ribonucleoprotein granules upon agrin bead stimulation. Given that our recent study reported the roles of membrane-type 1 matrix metalloproteinase (MT1-MMP) in agrin-induced presynaptic differentiation, here we further showed that MT1-MMP mRNA is spatially enriched and locally translated at sites induced by agrin beads. Taken together, this study reveals an essential role for axonal MT1-MMP translation, on top of the well-recognized long-range transport of MT1-MMP proteins synthesized from neuronal cell bodies, in mediating agrin-induced presynaptic differentiation.
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http://dx.doi.org/10.1242/dev.199000DOI Listing
May 2021

Ginkgo biloba leaf extract suppresses intestinal human breast cancer resistance protein expression in mice: Correlation with gut microbiota.

Biomed Pharmacother 2021 Aug 16;140:111712. Epub 2021 May 16.

Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address:

In this study, we investigated the effects of treatment with Gingko biloba leaf extract (GLE) on intestinal transporter expression and gut microbiota composition in mice and the correlation between intestinal transporter expression and gut microbiota composition in mice. When GLE was orally administered to mice, intestinal BCRP expression was significantly suppressed. Pharmacokinetic studies showed that the maximum plasma concentration and area under the curve values of sulfasalazine were increased more than twice by treatment with GLE compared with those in the control group. GLE treatment significantly decreased the populations of Proteobacteria and Deferribacteres at the phylum level. Correlation analysis showed that BCRP expression was positively or negatively correlated with the composition of gut bacteria. In Caco-2 cells, GLE treatment did not affect BCRP expression, but treatment with the lysates of GLE-treated mouse feces significantly suppressed BCRP expression. These findings demonstrate that the suppression of intestinal BCRP expression following GLE treatment may occur through modulation of the gut microbiota composition. Thus, the present study suggests that modulation of gut microbiota composition may cause drug transporter-mediated herb-drug interactions.
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http://dx.doi.org/10.1016/j.biopha.2021.111712DOI Listing
August 2021

CG6015 controls spermatogonia transit-amplifying divisions by epidermal growth factor receptor signaling in Drosophila testes.

Cell Death Dis 2021 05 14;12(5):491. Epub 2021 May 14.

Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, China.

Spermatogonia transit-amplifying (TA) divisions are crucial for the differentiation of germline stem cell daughters. However, the underlying mechanism is largely unknown. In the present study, we demonstrated that CG6015 was essential for spermatogonia TA-divisions and elongated spermatozoon development in Drosophila melanogaster. Spermatogonia deficient in CG6015 inhibited germline differentiation leading to the accumulation of undifferentiated cell populations. Transcriptome profiling using RNA sequencing indicated that CG6015 was involved in spermatogenesis, spermatid differentiation, and metabolic processes. Gene Set Enrichment Analysis (GSEA) revealed the relationship between CG6015 and the epidermal growth factor receptor (EGFR) signaling pathway. Unexpectedly, we discovered that phosphorylated extracellular regulated kinase (dpERK) signals were activated in germline stem cell (GSC)-like cells after reduction of CG6015 in spermatogonia. Moreover, Downstream of raf1 (Dsor1), a key downstream target of EGFR, mimicked the phenotype of CG6015, and germline dpERK signals were activated in spermatogonia of Dsor1 RNAi testes. Together, these findings revealed a potential regulatory mechanism of CG6015 via EGFR signaling during spermatogonia TA-divisions in Drosophila testes.
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http://dx.doi.org/10.1038/s41419-021-03783-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121936PMC
May 2021

Nanocellulose-derived carbon/g-CN heterojunction with a hybrid electron transfer pathway for highly photocatalytic hydrogen peroxide production.

J Colloid Interface Sci 2021 Oct 24;599:507-518. Epub 2021 Apr 24.

College of Material Engineering, Fujian Agriculture and Forestry University, Fuzhou 350108, China.

Using oxygen reduction for the photocatalytic production of hydrogen peroxide (HO) has been considered a green and sustainable route. In the present study, to achieve high efficiency, graphitic carbon nitride (g-CN) was obtained using thermal polymerization from a bi-component precursor and was then assembled with cellulose nanofibers. It was found that a small quantity of cellulose nanofibers that generates carbon fibers upon pyrolysis greatly improves the photocatalytic activity compared with that of g-CN alone. The well-defined carbon/g-CN heterojunction-type material exhibits as high as 1.10 mmol Lh of photo-production of HO under visible light, which is 4.2 times higher than that yielded by pristine g-CN from a single precursor. A comprehensive characterization of the photocatalyst enables us to delineate the effect of the carbon nanofiber with respect to porosity, electron-hole separation, band gap regulation, and especially the electron transfer pathway. Our results demonstrate that nanocellulose-derived carbon, when precisely assembled with other functional material such as a photocatalyst, is a promising promoter of their activity.
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http://dx.doi.org/10.1016/j.jcis.2021.04.111DOI Listing
October 2021

Genome-wide identification and functional analysis of long non-coding RNAs and mRNAs in male mice testes at the onset of puberty after low dose lead exposure.

Toxicol Appl Pharmacol 2021 07 28;422:115556. Epub 2021 Apr 28.

Department of Preventive Medicine, School of Health Sciences, Wuhan University, Wuhan, 430071, Hubei Province, China. Electronic address:

Many researchers have studied the relationship between lead (Pb) and testis injury, but the underlying mechanisms are still unknown. The participation of long non-coding RNAs (lncRNAs) in biological processes has been proposed. To comprehensively gain insight into the molecular toxicity of Pb, expression patterns are analysed through RNA sequencing (RNA-seq) in male mice treated with 200 mg/L of Pb through the drinking water for 90 days at the onset of puberty. A total of 614 differentially expressed (DE) lncRNAs were included (p ≤ 0.05 and fold change ≥2), of which 288 were up-regulated, and 326 were down-regulated. A total of 2295 DE mRNAs (p ≤ 0.05 and fold change ≥2), including 1202 up-regulated and 1093 down-regulated ones, were found in the testes of Pb-exposed group. Functional analysis results showed that several lncRNAs might be implicated in the bio-pathway of mitogen-activated protein kinase (MAPK) signaling pathway. Finally, seven pairs of lncRNA-mRNA co-expression were established in mice testes and confirmed by RT-qPCR. Moreover, the DE genes were also altered in Sertoli cells. Therefore, our research might be helpful for future exploring the effects of Pb exposure on lncRNA in testis, as well as its function.
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http://dx.doi.org/10.1016/j.taap.2021.115556DOI Listing
July 2021

BMI1 Drives Steroidogenesis Through Epigenetically Repressing the p38 MAPK Pathway.

Front Cell Dev Biol 2021 13;9:665089. Epub 2021 Apr 13.

Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, China.

Testosterone biosynthesis progressively decreases in aging males primarily as a result of functional changes to Leydig cells. Despite this, the mechanisms underlying steroidogenesis remain largely unclear. Using gene knock-out approaches, we and others have recently identified as an anti-aging gene. Herein, we investigate the role of BMI1 in steroidogenesis using mouse MLTC-1 and primary Leydig cells. We show that BMI1 can positively regulate testosterone production. Mechanistically, in addition to its known role in antioxidant activity, we also report that p38 mitogen-activated protein kinase (MAPK) signaling is activated, and testosterone levels reduced, in BMI1-deficient cells; however, the silencing of the p38 MAPK pathway restores testosterone production. Furthermore, we reveal that BMI1 directly binds to the promoter region of , an upstream activator of p38, thereby modulating its chromatin status and repressing its expression. Consequently, this results in the inhibition of the p38 MAPK pathway and the promotion of steroidogenesis. Our study uncovered a novel epigenetic mechanism in steroidogenesis involving BMI1-mediated gene silencing and provides potential therapeutic targets for the treatment of hypogonadism.
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http://dx.doi.org/10.3389/fcell.2021.665089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076678PMC
April 2021

Dopamine receptor agonists ameliorate bleomycin-induced pulmonary fibrosis by repressing fibroblast differentiation and proliferation.

Biomed Pharmacother 2021 Jul 23;139:111500. Epub 2021 Apr 23.

Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, 1095 Jiefang Ave, Wuhan 430030, China. Electronic address:

Idiopathic pulmonary fibrosis (IPF) is the most common fatal interstitial lung disease, with limited therapeutic options. The abnormal and uncontrolled differentiation and proliferation of fibroblasts have been confirmed to play a crucial role in driving the pathogenesis of IPF. Therefore, effective and well-tolerated antifibrotic agents that interfere with fibroblasts would be an ideal treatment, but no such treatments are available. Remarkably, we found that dopamine (DA) receptor D1 (D1R) and DA receptor D2 (D2R) were both upregulated in myofibroblasts in lungs of IPF patients and a bleomycin (BLM)-induced mouse model. Then, we explored the safety and efficacy of DA, fenoldopam (FNP, a selective D1R agonist) and sumanirole (SMR, a selective D2R agonist) in reversing BLM-induced pulmonary fibrosis. Further data showed that DA receptor agonists exerted potent antifibrotic effects in BLM-induced pulmonary fibrosis by attenuating the differentiation and proliferation of fibroblasts. Detailed pathway analysis revealed that DA receptor agonists decreased the phosphorylation of Smad2 induced by TGF-β1 in primary human lung fibroblasts (PHLFs) and IMR-90 cells. Overall, DA receptor agonists protected mice from BLM-induced pulmonary fibrosis and may be therapeutically beneficial for IPF patients in a clinical setting.
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http://dx.doi.org/10.1016/j.biopha.2021.111500DOI Listing
July 2021

Design and tailoring of two-dimensional Schottky, PN and tunnelling junctions for electronics and optoelectronics.

Nanoscale 2021 Apr 7;13(14):6713-6751. Epub 2021 Apr 7.

State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China.

Owing to their superior carrier mobility, strong light-matter interactions, and flexibility at the atomically thin thickness, two-dimensional (2D) materials are attracting wide interest for application in electronic and optoelectronic devices, including rectifying diodes, transistors, memory, photodetectors, and light-emitting diodes. At the heart of these devices, Schottky, PN, and tunneling junctions are playing an essential role in defining device function. Intriguingly, the ultrathin thickness and unique van der Waals (vdW) interlayer coupling in 2D materials has rendered enormous opportunities for the design and tailoring of various 2D junctions, e.g. using Lego-like hetero-stacking, surface decoration, and field-effect modulation methods. Such flexibility has led to marvelous breakthroughs during the exploration of 2D electronics and optoelectronic devices. To advance further, it is imperative to provide an overview of existing strategies for the engineering of various 2D junctions for their integration in the future. Thus, in this review, we provide a comprehensive survey of previous efforts toward 2D Schottky, PN, and tunneling junctions, and the functional devices built from them. Though these junctions exhibit similar configurations, distinct strategies have been developed for their optimal figures of merit based on their working principles and functional purposes.
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http://dx.doi.org/10.1039/d1nr00318fDOI Listing
April 2021

LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target.

Oncogene 2021 May 21;40(19):3422-3433. Epub 2021 Apr 21.

Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.

Peritoneal metastasis is a common form of metastasis among advanced gastric cancer patients. In this study, we reported the identification of LIM domain kinase 1 (LIMK1) as a promoter of gastric cancer peritoneal metastasis, and its potential to be a therapeutic target of dabrafenib (DAB). Using transcriptomic sequencing of paired gastric cancer peritoneal metastasis, primary tumors, and normal gastric tissues, we first unveiled that LIMK1 is selectively up-regulated in metastatic tumors. Increased LIMK1 in gastric cancer peritoneal metastasis was validated by immunohistochemistry analysis of an independent patient cohort. In vitro functional studies demonstrated that LIMK1 knockout or knockdown significantly inhibited cell migration and invasion of gastric cancer cells. LIMK1 knockout also abrogated peritoneal and liver metastases of gastric cancer cells in nude mice in vivo. Dabrafenib, a small molecule targeting LIMK1, was found to decrease cell migration and invasion of gastric cancer cells in vitro and abolish peritoneal and liver metastasis formation in vivo. Mechanistically, either LIMK1 knockout or Dabrafenib inhibited LIMK1 expression and phosphorylation of its downstream target cofilin. Taken together, our results demonstrated that LIMK1 functions as a metastasis promoter in gastric cancer by inhibiting LIMK1-p-cofilin and that Dabrafenib has the potential to serve as a novel treatment for gastric cancer peritoneal metastasis.
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http://dx.doi.org/10.1038/s41388-021-01656-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116207PMC
May 2021

Artificial intelligence and metagenomics in intestinal diseases.

J Gastroenterol Hepatol 2021 Apr;36(4):841-847

Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.

Gut microbiota has been shown to associate with the development of gastrointestinal diseases. In the last decade, development in whole metagenome sequencing and 16S rRNA sequencing technology has dramatically accelerated the gut microbiome's research and revealed its association with gastrointestinal disorders. Because of high dimensionality and complexity's intrinsic data characteristics, traditional bioinformatical methods could only explain the most significant changes with limited prediction accuracy. In contrast, machine learning is the application of artificial intelligence that provides the computational systems to automatically learn and improve from experience (training cohort) without being explicitly programmed. It is thus capable of unwiring high dimensionality and complicated correlational hitches. With modern computation power, machine learning is widely utilized to analyze microorganisms related to disease onset and other clinical features. It could help explore and identify novel biomarkers or improve the accuracy rate of disease diagnostic. This review summarized the most recent research that utilized machine learning to reveal the role of gut microbiota in intestinal disorders.
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http://dx.doi.org/10.1111/jgh.15501DOI Listing
April 2021

Machine learning on microbiome research in gastrointestinal cancer.

J Gastroenterol Hepatol 2021 Apr;36(4):817-822

Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.

Gastrointestinal cancer maintains the highest incidence and mortality rate among all cancers globally. In addition to genetic causes, it has been reported that individuals' diet and composition of the gastrointestinal microbiome have profound impacts on gastrointestinal cancer development. Microbiome research has risen in popularity to provide alternative insights into cancer development and potential therapeutic effect. However, there is a lack of an effective analytical tool to comprehend the massive amount of data generated from high-throughput sequencing methods. Artificial intelligence is another rapidly developing field that has strong application potential in microbiome research. Deep learning and machine learning are two subfields under the umbrella of artificial intelligence. Here we discuss the current approaches to study the gut microbiome, as well as the applications and challenges of implementing artificial intelligence in microbiome research.
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http://dx.doi.org/10.1111/jgh.15502DOI Listing
April 2021

Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance the HIF-1α/glycolysis Pathway.

Front Immunol 2021 31;12:649463. Epub 2021 Mar 31.

Center for Metabolic Disease Research and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States.

Macrophages polarized to different phenotypes critically contribute to colitis development by coordinating inflammatory and anti-inflammatory processes. Herein, targeting the balance between the pro-inflammatory M1 and the anti-inflammatory M2 macrophage phenotypes can be a novel therapeutic approach for colitis. In the present study, we firstly demonstrated that tiliroside possessed the ability to alleviate the clinical symptoms of colitis as evidenced by decreased disease activity index (DAI) scores, longer colon length, reduced myeloperoxidase (MPO) activity, and improvement of colonic pathological damage . Furthermore, we showed that tiliroside modulated the balance between M1 and M2 macrophages toward a more anti-inflammatory status in colonic lamina propria but has little effect on the T cell population and epithelial barrier function in colitis mice. The macrophage depletion study further showed the protective effect of tiliroside was macrophage dependent . Mechanistically, our study demonstrated that tiliroside regulated cellular metabolism by inhibiting aerobic glycolysis in LPS and IFNγ stimulated macrophages. At the molecular level, tiliroside facilitated the proteasomal degradation of HIF-1α and downregulated mRNA expressions of HIF-1α dependent glycolytic enzymes in macrophages. Collectively, our data highlight the aberrant M1/M2 macrophage polarization in the initiation and development of ulcerative colitis and put forth the stage for considering tiliroside as a metabolic regulator in reprogramming macrophage polarization, which may serve as a promising therapeutic approach for treatment of inflammation-associated and metabolic disorders.
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http://dx.doi.org/10.3389/fimmu.2021.649463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044352PMC
March 2021

Short-term assessment of radial artery grafts with multidetector computed tomography.

J Cardiothorac Surg 2021 Apr 17;16(1):93. Epub 2021 Apr 17.

Structural Heart Disease Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China.

Background: The clinical use of the radial artery (RA) in coronary artery bypass grafting (CABG) is still limited worldwide, although it has been recommended by several guidelines. Multidetector computed tomography (MDCT) is widely used to evaluate graft patency, as invasive coronary angiography could cause potentially serious risks including bleeding, dissection and stroke. This study aims to report the short-term results of the RA in CABG with MDCT.

Methods: The study population consists of 41 consecutive patients undergoing elective CABG with the RA graft between 2017 to 2018, with MDCT performed to evaluate graft patency during follow-up, and target vessels for the RA were non-left anterior descending coronary arteries with > 70% stenosis.

Results: A total of 150 grafts were assessed by MDCT during follow-up (mean, 8.9 ± 5.1 months). MDCT could clearly show the structure and patency of grafts, even for complex coronary artery revascularization. Graft patency of the left internal mammary artery was 92.9% (39/42), with the RA patency of 84.4% (38/45) and the patency of the saphenous vein graft of 81.1% (30/37). And the RA anastomosed to the left coronary artery system might have better patency than the RA anastomosed to the right coronary artery system (25/29, 86.2% vs 13/16, 81.3%, p = 0.686).

Conclusions: The short-term patency rate of RA grafts is good, and the RA might be associated with better patency when anastomosed to the left but not the right coronary artery. MDCT could provide excellent visualization of grafts in CABG.
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http://dx.doi.org/10.1186/s13019-021-01465-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052742PMC
April 2021
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