Publications by authors named "Mingyu Liu"

76 Publications

Meis homeobox 2 (MEIS2) inhibits the proliferation and promotes apoptosis of thyroid cancer cell and through the NF-κB signaling pathway.

Bioengineered 2021 Dec;12(1):1766-1772

Department of Otolaryngology Head and Neck Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Investigation of effects of Meis homeobox 2 (MEIS2) on proliferation and apoptosis of thyroid cancer (TC) cells and its specific molecular mechanism is the main purpose of this study. In this study, we found that the expression of MEIS2 was down-regulated in TC tissues and cell lines (B-CPAP, TPC-1 and K1), compared to adjacent histologically normal tissues and normal thyroid cell (Nthy-ori 3-1). Then, overexpression of MEIS2 promoted B-CPAP cell apoptosis and decreased cell proliferation, viability and cell cycle progression. Further studies confirmed that overexpression of MEIS2 could significantly decrease p65 expression in the nucleus of B-CPAP cells. However, the opposite results were presented after interference of MEIS2 expression. Taken together, MEIS2 expression was significantly down-regulated in TC. In addition, MEIS2 could inhibit NF-κB pathway activation, so as to perform both suppression of the viability and proliferation of TC cells and promotion of apoptosis.
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http://dx.doi.org/10.1080/21655979.2021.1923354DOI Listing
December 2021

Optimized Intracellular Staining Reveals Heterogeneous Cytokine Production Ability of Murine and Human Hematopoietic Stem and Progenitor Cells.

Front Immunol 2021 14;12:654094. Epub 2021 Apr 14.

MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.

Under stress conditions, hematopoietic stem and progenitor cells (HSPCs) can translate danger signals into a plethora of cytokine signals. These cytokines, or more precisely their combination, instruct HSPCs to modify the magnitude and composition of hematopoietic output in response to the threat, but investigations into the heterogeneous cytokine expression and regulatory mechanisms are hampered by the technical difficulty of measuring cytokine levels in HSPCs at the single-cell level. Here, we optimized a flow cytometry-based method for the simultaneous assessment of multiple intracellular cytokines in HSPCs. By selecting an optimal combination of cytokine restimulation reagents, protein transport inhibitors, and culture supplements, an optimized restimulation protocol for intracellular staining was developed. Using this method, we successfully examined expression levels of granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in murine and human HSPC subsets under steady-state or different stress conditions. Different cytokine expression patterns were observed, suggesting distinct regulatory modes of cytokine production dependent on the HSPC subset, cytokine, disease, organ, and species. Collectively, this technical advance may help to obtain a better understanding of the nature of HSPC heterogeneity on the basis of differential cytokine production.
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http://dx.doi.org/10.3389/fimmu.2021.654094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079767PMC
April 2021

Exploring the Relationship between Attitudes, Risk Perceptions, Fatalistic Beliefs, and Pedestrian Behaviors in China.

Int J Environ Res Public Health 2021 03 24;18(7). Epub 2021 Mar 24.

Human Factors Engineering, Transportation Research Group, University of Southampton, Southampton SO16 7QF, UK.

Road safety has become a worldwide public health concern. Although many factors contribute to collisions, pedestrian behaviors can strongly influence road safety outcomes. This paper presents results of a survey investigating the effects of age, gender, attitudes towards road safety, fatalistic beliefs and risk perceptions on self-reported pedestrian behaviors in a Chinese example. The study was carried out on 543 participants (229 men and 314 women) from 20 provinces across China. Pedestrian behaviors were assessed by four factors: errors, violations, aggressions, and lapses. Younger people reported performing riskier pedestrian behaviors compared to older people. Gender was not an influential factor. Of the factors explored, attitudes towards road safety explained the most amount of variance in self-reported behaviors. Significant additional variance in risky pedestrian behaviors was explained by the addition of fatalistic beliefs. The differences among the effects, and the implications for road safety intervention design, are discussed. In particular, traffic managers can provide road safety education and related training activities to influence pedestrian behaviors positively.
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http://dx.doi.org/10.3390/ijerph18073378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037076PMC
March 2021

Recovery preparedness of global air transport influenced by COVID-19 pandemic: Policy intervention analysis.

Transp Policy (Oxf) 2021 Jun 26;106:54-63. Epub 2021 Mar 26.

Institute for Transport Planning and Systems, ETH Zürich, Zürich, 8093, Switzerland.

The outbreak of COVID-19 constitutes an unprecedented disruption globally, in which risk management framework is on top priority in many countries. Travel restriction and home/office quarantine are some frequently utilized non-pharmaceutical interventions, which bring the worst crisis of airline industry compared with other transport modes. Therefore, the post-recovery of global air transport is extremely important, which is full of uncertainty but rare to be studied. The explicit/implicit interacted factors generate difficulties in drawing insights into the complicated relationship and policy intervention assessment. In this paper, a Causal Bayesian Network (CBN) is utilized for the modelling of the post-recovery behaviour, in which parameters are synthesized from expert knowledge, open-source information and interviews from travellers. The tendency of public policy in reaction to COVID-19 is analyzed, whilst sensitivity analysis and forward/backward belief propagation analysis are conducted. Results show the feasibility and scalability of this model. On condition that no effective health intervention method (vaccine, medicine) will be available soon, it is predicted that nearly 120 days from May 22, 2020, would be spent for the number of commercial flights to recover back to 58.52%-60.39% on different interventions. This intervention analysis framework is of high potential in the decision making of recovery preparedness and risk management for building the new normal of global air transport.
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http://dx.doi.org/10.1016/j.tranpol.2021.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995335PMC
June 2021

A risk score based on baseline risk factors for predicting mortality in COVID-19 patients.

Curr Med Res Opin 2021 Apr 10:1-11. Epub 2021 Apr 10.

Department of Orthopedics, The First People's Hospital of Jingmen affiliated to Hubei Minzu University, Jingmen, China.

Background: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources.

Methods: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses.

Results: Eight factors, namely, xygen saturation, blood rea nitrogen, espiratory rate, admission before the date the national aximum number of daily new cases was reached, ge, rocalcitonin, -reactive protein (CRP), and absolute eutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71;  < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts.

Conclusions: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.
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http://dx.doi.org/10.1080/03007995.2021.1904862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054492PMC
April 2021

Association between angiotensin converting enzyme gene polymorphism and essential hypertension: A systematic review and meta-analysis.

J Renin Angiotensin Aldosterone Syst 2021 Jan-Dec;22(1):1470320321995074

Department of Cardiology, Ninth Hospital of Wuhan, Wuhan City, Hubei Province, China.

Background: The current meta-analytic study explored the relation between ACE gene insertion/deletion (I/D), and the risk of EH by reviewing relevant trials so as to determine the association between Angiotensin Converting Enzyme (ACE) gene polymorphism and essential hypertension (EH) susceptibility.

Methods: Relevant studies published before May 2019 were collected from the PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP databases.

Results: Fifty-seven studies involving a total of 32,862 patients were included. These studies found that ACE gene D allele was associated with higher EH susceptibility in allelic model, homozygote model, dominant model, and regressive model, and that Asian population with ACE gene D allele showed a higher EH susceptibility in all these models. Moreover, ACE gene D allele was found closely related to a higher EH susceptibility in the subgroups of HWE, NO HWE, Caucasian population, and Mixed population, with the majority being males in allelic model, homozygote model, and regressive model and the majority being females in allelic model.

Conclusion: ACE gene D allele is associated with an overall higher EH susceptibility, which is confirmed in the subgroup analysis of Asian population, HWE, NO HWE, Caucasian population, and Mixed population.
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http://dx.doi.org/10.1177/1470320321995074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983243PMC
March 2021

Icaritin Induces Anti-tumor Immune Responses in Hepatocellular Carcinoma by Inhibiting Splenic Myeloid-Derived Suppressor Cell Generation.

Front Immunol 2021 26;12:609295. Epub 2021 Feb 26.

Ministry of Education Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Recent studies have demonstrated that splenic extramedullary hematopoiesis (EMH) is an important mechanism for the accumulation of myeloid-derived suppressor cells (MDSCs) in tumor tissues, and thus contributes to disease progression. Icaritin, a prenylflavonoid derivative from plants of the genus, has been implicated as a novel immune-modulator that could prolong the survival of hepatocellular carcinoma (HCC) patients. However, it is unclear whether icaritin achieves its anti-tumor effects via the regulation of MDSCs generated by EMH in HCC. Here, we investigated the anti-tumor potential of icaritin and its mechanism of action in murine HCC. Icaritin suppressed tumor progression and significantly prolonged the survival of mice-bearing orthotopic and subcutaneous HCC tumors. Rather than exerting direct cytotoxic activity against tumor cells, icaritin significantly reduced the accumulation and activation of tumoral and splenic MDSCs, and increased the number and activity of cytotoxic T cells. Mechanistically, icaritin downregulates the tumor-associated splenic EMH, thereby reducing the generation and activation of MDSCs. The inhibitory effects of icaritin on human MDSCs were verified in short-term culture with cord-blood derived hematopoietic precursors. Furthermore, icaritin synergistically enhanced the therapeutic efficacy of immune checkpoint blockade therapy in HCC mice. These findings revealed that icaritin dampens tumoral immunosuppression to elicit anti-tumor immune responses by preventing MDSC generation via the attenuation of EMH. Thus, icaritin may serve as a novel adjuvant or even a stand-alone therapeutic agent for the effective treatment of HCC.
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http://dx.doi.org/10.3389/fimmu.2021.609295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952329PMC
February 2021

Selective removal of anionic dyes in single and binary system using Zirconium and iminodiacetic acid modified magnetic peanut husk.

Environ Sci Pollut Res Int 2021 Mar 13. Epub 2021 Mar 13.

College of Chemistry, Zhengzhou University, No 100 of Kexue Road, Zhengzhou, 450001, People's Republic of China.

A novel adsorbent (PN-FeO-IDA-Zr) was developed from the chemical modification of peanut husk (a low cost material) with FeO, iminodiacetic acid (IDA) and zirconium (Zr) and its efficacy for the sequestration of wastewater assessed using Alizarin red (AR) and Acid chrome blue K (AK) as model pollutants. To elucidate the characteristics of the formed adsorbent, analytical techniques such as the Bruauner-Emmet-Teller (BET) method, X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FTIR) spectroscopy, X-ray diffractive spectroscopy (XRD) and vibrating sample magnetometer (VSM) were applied. Results from these studies confirmed the formation of a crystalline mesoporous adsorbent with surface properties which enhanced its usefulness. From the adsorption studies, it was observed that factors such as pH, salts, temperature and contact time influenced the uptake of the anionic dyes. The maximum monolayer capacity of PN-FeO-IDA-Zr for AR was 49.4 mg g (at 313 K) and was well fitted by the Langmuir model with the chemisorption process being the dominant reaction mechanism. In binary systems, PN-FeO-IDA-Zr exhibited higher affinity for AR as compared with AK. The significant removal efficiency exhibited by this novel adsorbent as well as other unique features such as easy retrieval and high regeneration promotes its prospects as an adsorbent for practical wastewater remediation processes.
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http://dx.doi.org/10.1007/s11356-021-13030-5DOI Listing
March 2021

Atom-Economical Cross-Coupling of Internal and Terminal Alkynes to Access 1,3-Enynes.

J Am Chem Soc 2021 Mar 8;143(10):3881-3888. Epub 2021 Mar 8.

Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, United States.

Selective carbon-carbon (C-C) bond formation in chemical synthesis generally requires prefunctionalized building blocks. However, the requisite prefunctionalization steps undermine the overall efficiency of synthetic sequences that rely on such reactions, which is particularly problematic in large-scale applications, such as in the commercial production of pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without prefunctionalized building blocks. In this transformation several classes of unactivated internal acceptor alkynes can be coupled with terminal donor alkynes to deliver 1,3-enynes in a highly regio- and stereoselective manner. The scope of compatible acceptor alkynes includes propargyl alcohols, (homo)propargyl amine derivatives, and (homo)propargyl carboxamides. This method is facilitated by a tailored P,N-ligand that enables regioselective addition and suppresses secondary /-isomerization of the product. The reaction is scalable and can operate effectively with as low as 0.5 mol % catalyst loading. The products are versatile intermediates that can participate in various downstream transformations. We also present preliminary mechanistic experiments that are consistent with a redox-neutral Pd(II) catalytic cycle.
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http://dx.doi.org/10.1021/jacs.0c12565DOI Listing
March 2021

Susceptibility-associated genetic variation in NEDD9 contributes to prostate cancer initiation and progression.

Cancer Res 2021 Feb 25. Epub 2021 Feb 25.

Center for Personalized Cancer Therapy, Uiversity of Massachusetts Boston

Although American men of European ancestry represent the largest population of prostate cancer (PCa) patients, men of African ancestry are disproportionately affected by PCa with higher prevalence and worse outcomes. These racial disparities in PCa are due to multiple factors, but variations in genomic susceptibility such as single nucleotide polymorphisms (SNP) may play an important role in determining cancer aggressiveness and treatment outcome. Using public databases, we have identified a PCa susceptibility SNP at an intronic enhancer of the NEDD9 gene, which is strongly associated with increased risk of patients with African ancestry. This genetic variation increased expression of NEDD9 by modulating the chromatin binding of certain transcription factors, including ERG and NANOG. Moreover, NEDD9 displayed oncogenic activity in PCa cells, promoting PCa tumor growth and metastasis in vitro and in vivo. Together, our study provides novel insights into the genetic mechanisms driving PCa racial disparities.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3042DOI Listing
February 2021

Outcomes and prognostic factors in 70 non-survivors and 595 survivors with COVID-19 in Wuhan, China.

Transbound Emerg Dis 2020 Dec 30. Epub 2020 Dec 30.

Wuhan Ninth Hospital, Wuhan, China.

Since the first outbreak of coronavirus disease 2019 (COVID-19) occurred in December 2019, more than 51 million cases had been reported globally. We aimed to identify the risk factors for in-hospital fatal outcome and severe pneumonia of this disease. This is a retrospective, multicentre study, which included all confirmed cases of COVID-19 with definite outcomes (died or discharged) hospitalized between 1 January and 4 March 2020 in Wuhan. Of all 665 patients included, 70 died and 595 discharged (including 333 mild and 262 severe cases). Underlying comorbidity was more commonly observed among deaths (72.9%) than mild (26.4%) and severe (61.5%) survivors, with hypertension, diabetes and cardiovascular as dominant diseases. Fever and cough were the primary clinical magnifications. Older age (≥65 years) (OR = 3.174, 95% CI = 1.356-7.755), diabetes (OR = 2.540, 95% CI = 0.995-6.377), dyspnoea (OR = 7.478, 95% CI = 3.031-19.528), respiratory failure (OR = 10.528, 95% CI = 4.484-25.829), acute cardiac injury (OR = 25.103, 95% CI = 9.057-76.590) and acute respiratory distress syndrome (OR = 7.308, 95% CI = 1.501-46.348) were associated with in-hospital fatal outcome. In addition, older age (OR = 2.149, 95% CI = 1.424-3.248), diabetes (OR = 3.951, 95% CI = 2.077-7.788), cardiovascular disease (OR = 3.414, 95% CI = 1.432-8.799), nervous system disease (OR = 4.125, 95% CI = 1.252-18.681), dyspnoea (OR = 31.944, 95% CI = 18.877-92.741), achieving highest in-hospital temperature of >39.0°C (OR = 37.450, 95% CI = 7.402-683.403) and longer onset of illness to diagnosis (≥9 days) were statistically associated with higher risk of developing severe COVID-19. In conclusion, the potential risk factors forolder age, diabetes, dyspnoea, respiratory failure, acute cardiac injury and acute respiratory distress syndrome could help clinicians to identify patients with poor prognosis at an early stage.
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http://dx.doi.org/10.1111/tbed.13969DOI Listing
December 2020

Complete chloroplast genome sequence of an alpine rhubarb .

Mitochondrial DNA B Resour 2020 Nov 3;5(3):3681-3682. Epub 2020 Nov 3.

State Key Laboratory of Grassland Agro-Ecosystem, Institute of Innovation Ecology, Lanzhou University, Lanzhou, China.

Samuelsson (Polygonaceae) is an endangered alpine rhubarb in the Qinghai-Tibet Plateau. In this study we report the complete chloroplast genome sequence (plastome) of . The assembled plastome is 162,291 bp in length with 31,741 bp inverted repeat (IR) regions and 128 annotated genes, including 34 tRNA genes, 8 rRNA genes, and 86 protein-coding genes. Phylogenetic analyses based on the full plastome sequences suggest the close relationship of with and . The plastome reported here is highly useful for designing plastome SSR markers to conduct a further conservation genetic study of this endangered rhubarb.
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http://dx.doi.org/10.1080/23802359.2020.1832930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646595PMC
November 2020

Engineering an Optogenetic CRISPRi Platform for Improved Chemical Production.

ACS Synth Biol 2021 01 24;10(1):125-131. Epub 2020 Dec 24.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

Microbial synthesis of chemicals typically requires the redistribution of metabolic flux toward the synthesis of targeted products. Dynamic control is emerging as an effective approach for solving the hurdles mentioned above. As light could control the cell behavior in a spatial and temporal manner, the optogenetic-CRISPR interference (opto-CRISPRi) technique that allocates the metabolic resources according to different optical signal frequencies will enable bacteria to be controlled between the growth phase and the production stage. In this study, we applied a blue light-sensitive protein EL222 to regulate the expression of the dCpf1-mediated CRISPRi system that turns off the competitive pathways and redirects the metabolic flux toward the heterologous muconic acid synthesis in . We found that the opto-CRISPRi system dynamically regulating the suppression of the central metabolism and competitive pathways could increase the muconic acid production by 130%. These results demonstrated that the opto-CRISPRi platform is an effective method for enhancing chemical synthesis with broad utilities.
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http://dx.doi.org/10.1021/acssynbio.0c00488DOI Listing
January 2021

Lemnardosinanes A-I: New Bioactive Sesquiterpenoids from Soft Coral sp.

J Org Chem 2021 01 15;86(1):970-979. Epub 2020 Dec 15.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.

Two rearranged nardosinane sesquiterpenoids with novel carbon skeletons, lemnardosinanes A () and B (), and seven new nardosinane-related sesquiterpeniod lemnardosinanes C-I (), together with a known compound 6,7-seco-13-nornardosinan (), were isolated from the soft coral sp. collected from Xisha Islands of the South China Sea. Their structures were elucidated by comprehensive spectroscopic analyses, Mosher's method, Mo(OAc)-induced circular dichroism experiment, and quantum chemical calculations. Plausible biosynthetic pathways of - were proposed. Compounds and displayed angiogenesis promoting activity in a zebrafish model. Compounds and exhibited antiviral activity against the H1N1 virus with IC values of 10.9 and 41.5 μM, respectively.
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http://dx.doi.org/10.1021/acs.joc.0c02463DOI Listing
January 2021

Role of a complex of two proteins in alleviating sodium ion stress in an economic crop.

Authors:
Jie Yang Mingyu Liu

PLoS One 2020 20;15(11):e0242221. Epub 2020 Nov 20.

Beijing Forestry University, Beijing, China.

An economically valuable woody plant species tree bean (Cajanus cajan (L.) Millsp.) is predominantly cultivated in tropical and subtropical areas and is regarded as an important food legume (or pulse) crop that is facing serious sodium ion stress. NAM (N-acetyl-5-methoxytryptamine) has been implicated in abiotic and biotic stress tolerance in plants. However, the role of NAM in sodium ion stress tolerance has not been determined. In this study, the effect of NAM was investigated in the economically valuable woody plant species, challenged with stress at 40 mM sodium ion for 3 days. NAM-treated plants (200 μM) had significantly higher fresh weight, average root length, significantly reduced cell size, increased cell number, and increased cytoskeleton filaments in single cells. The expression pattern of one of 10 Tree bean Dynamic Balance Movement Related Protein (TbDMP), TbDMP was consistent with the sodium ion-stress alleviation by NAM. Using TbDMP as bait, Dynamic Balance Movement Related Kinase Protein (TbDBK) was determined to interact with TbDMP by screening the tree bean root cDNA library in yeast. Biochemical experiments showed that NAM enhanced the interaction between the two proteins which promoted resist sodium ion stress resistance. This study provides evidence of a pathway through which the skeleton participates in NAM signaling.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242221PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679020PMC
December 2020

Fabrication of zirconium (IV)-loaded chitosan/FeO/graphene oxide for efficient removal of alizarin red from aqueous solution.

Carbohydr Polym 2020 Nov 24;248:116792. Epub 2020 Jul 24.

College of Chemistry, Zhengzhou University, No 100 of Kexue Road, Zhengzhou, 450001, PR China. Electronic address:

Zirconium(IV)-loaded chitosan/FeO/graphene oxide (Zr-CMGO) was fabricated and applied to remove alizarin red (AR) from aqueous solution. Characterizations of Zr-CMGO were performed using several techniques. The effects of initial AR pH, coexisted NaCl, contact time and AR concentration were systematically investigated in batch mode. The increased pH had a negative effect on AR adsorption while there was little impact with salinity. Adsorption capacity toward AR reached up to 231 mg/g at 313 K. The kinetic and isotherm analyses indicated that pseudo-second-order kinetic model and Freundlich model could predicted the uptake of AR. In addition, the mechanism of AR adsorption could be mainly complexation, electrostatic force, etc. There is antibacterial activity from test about Zr-CMGO. Furthermore, the two-stage design could be applied for the theoretical support. Based on all results, Zr-CMGO is a novel and selective adsorbent for practical applications.
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http://dx.doi.org/10.1016/j.carbpol.2020.116792DOI Listing
November 2020

On-machine surface defect detection using light scattering and deep learning.

J Opt Soc Am A Opt Image Sci Vis 2020 Sep;37(9):B53-B59

This paper presents an on-machine surface defect detection system using light scattering and deep learning. A supervised deep learning model is used to mine the information related to defects from light scattering patterns. A convolutional neural network is trained on a large dataset of scattering patterns that are predicted by a rigorous forward scattering model. The model is valid for any surface topography with homogeneous materials and has been verified by comparing with experimental data. Once the neural network is trained, it allows for fast, accurate, and robust defect detection. The system capability is validated on microstructured surfaces produced by ultraprecision diamond machining.
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http://dx.doi.org/10.1364/JOSAA.394102DOI Listing
September 2020

Chromatin binding of FOXA1 is promoted by LSD1-mediated demethylation in prostate cancer.

Nat Genet 2020 10 31;52(10):1011-1017. Epub 2020 Aug 31.

Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, USA.

FOXA1 functions as a pioneer transcription factor by facilitating the access to chromatin for steroid hormone receptors, such as androgen receptor and estrogen receptor, but mechanisms regulating its binding to chromatin remain elusive. LSD1 (KDM1A) acts as a transcriptional repressor by demethylating mono/dimethylated histone H3 lysine 4 (H3K4me1/2), but also acts as a steroid hormone receptor coactivator through mechanisms that are unclear. Here we show, in prostate cancer cells, that LSD1 associates with FOXA1 and active enhancer markers, and that LSD1 inhibition globally disrupts FOXA1 chromatin binding. Mechanistically, we demonstrate that LSD1 positively regulates FOXA1 binding by demethylating lysine 270, adjacent to the wing2 region of the FOXA1 DNA-binding domain. Acting through FOXA1, LSD1 inhibition broadly disrupted androgen-receptor binding and its transcriptional output, and dramatically decreased prostate cancer growth alone and in synergy with androgen-receptor antagonist treatment in vivo. These mechanistic insights suggest new therapeutic strategies in steroid-driven cancers.
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http://dx.doi.org/10.1038/s41588-020-0681-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541538PMC
October 2020

Anemia is associated with severe illness in COVID-19: A retrospective cohort study.

J Med Virol 2021 03 10;93(3):1478-1488. Epub 2020 Nov 10.

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

Anemia commonly aggravates the severity of respiratory diseases, whereas thus far, few studies have elucidated the impact of anemia on coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the clinical characteristics of patients with anemia, and to further explore the relationship between anemia and the severity of COVID-19. In this single-center, retrospective, observational study, a total of 222 confirmed patients admitted to Wuhan Ninth Hospital from 1 December 2019 to 20 March 2020 were recruited, including 79 patients with anemia and 143 patients without anemia. Clinical characteristics, laboratory findings, disease progression and prognosis were collected and analyzed. Risk factors associated with the severe illness in COVID-19 were established by univariable and multivariable logistic regression models. In our cohort, compared to patients without anemia, patients with anemia were more likely to have one or more comorbidities and severe COVID-19 illness. More patients demonstrated elevated levels of C-reactive protein (CRP), procalcitonin (PCT) and creatinine in anemia group. Levels of erythrocyte sedimentation rate, D-dimer, myoglobin, T-pro brain natriuretic peptide (T-pro-BNP) and urea nitrogen in patients with anemia were significantly higher than those without. In addition, the proportion of patients with dyspnea, elevated CRP, and PCT was positively associated with the severity of anemia. The odd ratio of anemia related to the severe condition of COVID-19 was 3.47 (95% confidence interval [CI]: 1.02-11.75; P = .046) and 3.77 (95% CI: 1.33-10.71; P = .013) after adjustment for baseline date and laboratory indices, respectively. Anemia is an independent risk factor associated with the severe illness of COVID-19, and healthcare professionals should be more sensitive to the hemoglobin levels of COVID-19 patients on admission. Awareness of anemia as a risk factor for COVID-19 was of great significance.
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http://dx.doi.org/10.1002/jmv.26444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461220PMC
March 2021

Early modulation of macrophage ROS-PPARγ-NF-κB signalling by sonodynamic therapy attenuates neointimal hyperplasia in rabbits.

Sci Rep 2020 07 15;10(1):11638. Epub 2020 Jul 15.

Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, 23 Youzheng Street, Harbin, 150001, China.

Disruption of re-endothelialization and haemodynamic balance remains a critical side effect of drug-eluting stents (DES) for preventing intimal hyperplasia. Previously, we found that 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) suppressed macrophage-mediated inflammation in atherosclerotic plaques. However, the effects on intimal hyperplasia and re-endothelialization remain unknown. In this study, 56 rabbits were randomly assigned to control, ultrasound, ALA and ALA-SDT groups, and each group was divided into two subgroups (n = 7) on day 3 after right femoral artery balloon denudation combined with a hypercholesterolemic diet. Histopathological analysis revealed that ALA-SDT enhanced macrophage apoptosis and ameliorated inflammation from day 1. ALA-SDT inhibited neointima formation without affecting re-endothelialization, increased blood perfusion, decreased the content of macrophages, proliferating smooth muscle cells (SMCs) and collagen but increased elastin by day 28. In vitro, ALA-SDT induced macrophage apoptosis and reduced TNF-α, IL-6 and IL-1β via the ROS-PPARγ-NF-κB signalling pathway, which indirectly inhibited human umbilical artery smooth muscle cell (HUASMC) proliferation, migration and IL-6 production. ALA-SDT effectively inhibits intimal hyperplasia without affecting re-endothelialization. Hence, its clinical application combined with bare-metal stent (BMS) implantation presents a potential strategy to decrease bleeding risk caused by prolonged dual-antiplatelet regimen after DES deployment.
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http://dx.doi.org/10.1038/s41598-020-68543-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363872PMC
July 2020

In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19.

Cell Metab 2020 08 24;32(2):176-187.e4. Epub 2020 Jun 24.

Department of Intensive Care Unit, Wuhan Third Hospital & Tongren Hospital of Wuhan University, Wuhan, China.

Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.
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http://dx.doi.org/10.1016/j.cmet.2020.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311917PMC
August 2020

Myeloid signature reveals immune contexture and predicts the prognosis of hepatocellular carcinoma.

J Clin Invest 2020 09;130(9):4679-4693

MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences.

BACKGROUNDDespite an increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the tumor-associated myeloid response balance and its translational value. We aimed to construct a simple and reliable myeloid signature for hepatocellular carcinoma (HCC).METHODSUsing in situ immunohistochemistry, we assessed the distribution of major myeloid subtypes in both peri- and intratumoral regions of HCC. A 2-feature-based, myeloid-specific prognostic signature, named the myeloid response score (MRS), was constructed using an L1-penalized Cox regression model based on data from a training subset (n = 244), a test subset (n = 244), and an independent internal (n = 341) and 2 external (n = 94; n = 254) cohorts.RESULTSThe MRS and the MRS-based nomograms displayed remarkable discriminatory power, accuracy, and clinical usefulness for predicting recurrence and patient survival, superior to current staging algorithms. Moreover, an increase in MRS was associated with a shift in the myeloid response balance from antitumor to protumor activities, accompanied by enhanced CD8+ T cell exhaustion patterns. Additionally, we provide evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC.CONCLUSIONWe identified and validated a simple myeloid signature for HCC that showed remarkable prognostic potential and may serve as a basis for the stratification of HCC immune subtypes.FUNDINGThis work was supported by the National Science and Technology Major Project of China, the National Natural Science Foundation of China, the Science and Information Technology of Guangzhou, the Fundamental Research Funds for the Central Universities, the Guangdong Basic and Applied Basic Research Foundation, and the China Postdoctoral Science Foundation.
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http://dx.doi.org/10.1172/JCI135048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456226PMC
September 2020

Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes.

Cell Metab 2020 06 1;31(6):1068-1077.e3. Epub 2020 May 1.

The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China.

Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.
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http://dx.doi.org/10.1016/j.cmet.2020.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252168PMC
June 2020

Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19.

Circ Res 2020 06 17;126(12):1671-1681. Epub 2020 Apr 17.

General Surgery, Huanggang Central Hospital, Wuhan, China (W.M.).

Rationale: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.

Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.

Methods And Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; =0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; =0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; =0.01) in patients with COVID-19 and coexisting hypertension.

Conclusions: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.317134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265882PMC
June 2020

Sesquiterpenoids from the soft coral sp.

Nat Prod Res 2020 Mar 9:1-5. Epub 2020 Mar 9.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, People's Republic of China.

Two new neolemnane-type sesquiterpenoids lemnolins A () and B (), together with one known tricyclic sesquiterpenoid () were isolated from the South China Sea soft coral sp. The structures were elucidated by comprehensive spectroscopic analysis and ECD analysis. Compound displayed antiviral activity against influenza A (H1N1) virus .
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http://dx.doi.org/10.1080/14786419.2020.1736062DOI Listing
March 2020

Recent applications of chiral phosphoric acids in palladium catalysis.

Org Biomol Chem 2020 01 7;18(4):618-637. Epub 2020 Jan 7.

Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, BCC-169, La Jolla, CA 92037, USA.

Through the combined action of palladium catalysts and chiral phosphoric acids (CPAs) a variety of catalytic asymmetric reactions have been realized during the past decade, including allylation, alkene functionalization, and C-H activation. This review surveys key examples across these various reaction types and examines the different mechanisms by which CPAs can affect stereoinduction in these reaction systems.
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http://dx.doi.org/10.1039/c9ob02205hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032947PMC
January 2020

Membrane-permeabilized sonodynamic therapy enhances drug delivery into macrophages.

PLoS One 2019 10;14(6):e0217511. Epub 2019 Jun 10.

Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China.

Macrophages play a pivotal role in the formation and development of atherosclerosis as a predominant inflammatory cell type present within atherosclerotic plaque. Promoting anti-atherosclerotic drug delivery into macrophages may provide a therapeutic potential on atherosclerotic plaque. In this study, we investigated whether membrane-permeabilized sonodynamic therapy (MP-SDT) enhances drug delivery into THP-1 macrophages. Images of confocal microscopy confirmed that the optimal plasma distribution of the sonosensitizer protoporphyrin IX (PpIX) was at 1 hour incubation. The non-lethal parameter of MP-SDT was determined by cell viability as measured by a CCK-8 assay. Bright field microscopy demonstrated plasma membrane deformation in response to MP-SDT. Using SYTOX Green, a model drug for cellular uptake, we found that MP-SDT significantly induced membrane permeabilization dependent on ultrasound intensity and exposure time. Using Fluo-3 AM, intracellular calcium elevation during MP-SDT was confirmed as a result of membrane permeabilization. Membrane perforation of MP-SDT-treated cells was observed by scanning electron microscopy and transmission electron microscopy. Moreover, MP-SDT-induced membrane permeabilization and perforation were remarkably prevented by scavenging reactive oxygen species (ROS) during MP-SDT. Furthermore, we assessed the therapeutic effect of MP-SDT in combination with anti-atherosclerotic drug atorvastatin. Our results showed that MP-SDT increased the therapeutic effect of atorvastatin on lipid-laden THP-1-derived foam cells, including decreasing lipid droplets, increasing the cholesterol efflux and the expression of PPARγ and ABCG1. In conclusion, MP-SDT might become a promising approach to facilitating the delivery of anti-atherosclerotic drugs into macrophages via membrane permeabilization.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217511PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557485PMC
March 2020

Propofol-induced miR-219-5p inhibits growth and invasion of hepatocellular carcinoma through suppression of GPC3-mediated Wnt/β-catenin signalling activation.

J Cell Biochem 2019 10 19;120(10):16934-16945. Epub 2019 May 19.

Department of Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.

Propofol is one of the most extensively used intravenous anaesthetic agents, which has been found to improve the surgical intervention outcome of several types of cancer, including hepatocellular carcinoma (HCC). Additionally, in vitro and in vivo experiments have also indicated that propofol affects the biological behaviour of HCC. However, the underlying mechanisms of the surgical resection of HCC with propofol have not been fully understood. In the present study, we aimed to investigate the underlying mechanism of propofol inhibition of the growth and invasion of HCC cells. Our results showed that treatment with propofol suppressed the proliferation, invasion and migration of HCC in vitro. The subcutaneous xenograft tumour and orthotopic xenograft tumour experiments in nude mice showed that propofol significantly decreased tumour volumes, growth rates and the liver orthotopic xenograft tumour in vivo. Furthermore, the underlying mechanism investigations of the suppressive effects of propofol on HCC cells revealed that propofol treatment upregulated the expression levels of the candidate tumour suppressor miR-219-5p. Silencing of propofol-induced miR-219-5p using anti-miR-219-5p abrogated the inhibitory effects on the proliferation, migration and invasion of HCC cells exerted by propofol treatment. Additionally, we demonstrated that propofol reversed the epithelial-mesenchymal transition of Huh7 and SMMC7721 cells via miR-219-5p induction. The molecular mechanism behind these findings is that propofol-induced miR-219-5p inhibits HCC cell progression by targeting glypican-3 and subsequently results in the inhibition of Wnt/β-catenin signalling. Taken together, our study provides new insights into the advantages of the surgical intervention of HCC with propofol anaesthetization.
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http://dx.doi.org/10.1002/jcb.28952DOI Listing
October 2019

Lipidomics coupled with pathway analysis characterizes serum metabolic changes in response to potassium oxonate induced hyperuricemic rats.

Lipids Health Dis 2019 May 10;18(1):112. Epub 2019 May 10.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.

Background: Hyperuricemia as a metabolic disease is usually associated with lipid metabolic disorder. The purpose of this study is to identify potential lipid biomarkers and provide the evidence for the relationship between hyperuricemia and lipid-related diseases.

Methods: Lipidomics-a specialized study of lipid metabolites-has become a highly sensitive and powerful tool for biomarker discovery. In this work, an ultra-performance liquid chromatography-quadruole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS)-based on Lipidomics approach was employed to investigate serum samples from potassium oxonate-treated rats to find potential biomarkers. Principal component analysis (PCA) was used to analyze the MS data to assess the establishment of hyperuricemia model. Orthogonal partial least-squares discriminant analysis (OPLS-DA) in combination with independent samples t-test was performed for biomarker selection and identification.

Results: Thirteen potential biomarkers in rat serum were identified in the screen, and two abnormal metabolism pathways were found, namely glycerolphospholipid metabolism and glycosylphosphatidylinositol-anchored protein biosynthesis.

Conclusions: In this work, the Lipidomics approach based on UPLC-Q-TOF/MS was employed to investigate serum metabolic changes in the rat model, 13 potential biomarkers related to hyperuricemia were identified, primarily involved in glycerolphospholipid metabolism and glycosylphosphatidylinositol-anchored protein biosynthesis. Abnormal glycerophospholipid metabolism pathway may be associated with lipid metabolism disorder caused by hyperuricemia, while the relationship between hyperuricemia and glycosylphosphatidylinositol-anchored protein biosynthesis needs further study.
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http://dx.doi.org/10.1186/s12944-019-1054-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511199PMC
May 2019

RAB18 promotes proliferation and metastasis in hepatocellular carcinoma.

Am J Transl Res 2019 15;11(2):1009-1019. Epub 2019 Feb 15.

Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University Guangzhou, China.

RAB18, a member of the Ras family, has been suggested to play a critical role in multiple biological process. However, its functions in the development of hepatocellular carcinoma (HCC) remain unknown. In the present study, the expression and biological role of RAB18 in HCC were investigated. Results showed that the expression level of RAB18 was significantly increased in HCC tissue specimens and HCC cell lines. Kaplan-Meier survival analysis showed that high RAB18 expression was correlated with poor overall survival compared to those with low RAB18 expression. These results were further confirmed by analyses in the Cancer Genome Atlas (TCGA) database. Specific knockdown of RAB18 expression inhibited proliferation and clone formation of HCC . Western blot analyses showed that CCND1 was suppressed, and p21 and p27 were substantially upregulated in RAB18 knockdown HCC cells. Furthermore, we also observed that knockdown of RAB18 expression suppressed the migration and invasion of HCC cells and reversed expression of epithelial-mesenchymal transition (EMT)-related markers. Interestingly, the primary and xenograft tumor mouse models showed that RAB18 knockdown significantly reduced tumorigenesis and metastasis in nude mice. These results revealed that RAB18 was correlated with poor clinical outcomes and facilitated HCC progression via promotion of HCC cell proliferation and metastasis. These findings suggest that RAB18 may be a prognostic biomarker and potential therapeutic target in patients with HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413289PMC
February 2019