Publications by authors named "Mei Liu"

1,209 Publications

  • Page 1 of 1

Effect of One-Coordinated Atoms on the Electronic and Optical Properties of ZnSe Clusters.

ACS Omega 2021 Jul 15;6(29):18711-18718. Epub 2021 Jul 15.

Institute of Atomic and Molecular Physics, Sichuan University, Chengdu, Sichuan 610065, P. R. China.

To understand the influence of one-coordinated Zn and Se atoms on the structures, electronic, and optical properties of ZnSe clusters, we investigate the ZnSe clusters employing first-principles theoretical calculations. The ZnSe cluster, constructed from the InP nanocrystal structure, possesses a ZnSe core and 16 one-coordinated surface atoms. The effect of one-coordinated atoms is studied by adding or removing one-coordinated atoms of the ZnSe cluster. The calculations show that the modifications of one-coordinated atoms change slightly the coordination states and bond lengths of the atoms on the cluster surface. The clusters with the same core structure and different amounts of one-coordinated atoms have similar optical spectra, suggesting the importance of the cluster core structure in their optical properties.
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http://dx.doi.org/10.1021/acsomega.1c01550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319925PMC
July 2021

Inhibition of USP11 sensitizes gastric cancer to chemotherapy via suppressing RhoA and Ras-mediated signaling pathways.

Clin Res Hepatol Gastroenterol 2021 Jul 28:101779. Epub 2021 Jul 28.

Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, People's Republic of China. Electronic address:

Background: The poor outcomes in advanced gastric cancer (GC) necessitate alternative therapeutic strategy. Ubiquitin-specific protease 11 (USP11) has recently garnered attention as a therapeutic target in cancer because of its important regulatory role in cancer cell functions. Here, we revealed the expression, function and underlying molecular interactions of USP11 in gastric cancer.

Methods: The expression of USP11 was analyzed using immunohistochemistry and ELISA. The loss-of function and gain-of function analysis of USP11 was performed using siRNA knockdown and plasmid overexpression approaches. The downstream molecules regulated by USP11 were determined using immunoblotting analysis.

Results: USP11 was upregulated in ∼80% of gastric cancer patients, and the upregulation was associated with HER3 overexpression. In addition, USP11 level was not regulated by HER3 and vice versa. Functional studies demonstrated that USP11 overexpression promoted gastric cancer growth and migration, and alleviated toxicity-induced by chemotherapeutic drug. In contrast, USP11 depletion significantly inhibited gastric cancer growth, migration and survival, and augmented chemotherapeutic drug's efficacy. Gastric cancer cells with higher USP11 levels were more sensitive to USP11 inhibitions than cells with lower USP11 levels. Mechanism studies showed that USP11 depletion suppressed migration via RhoA-mediated pathway and inhibited growth and survival likely via Ras-mediated pathway.

Conclusions: Our work highlights the important role of USP11 in gastric cancer and therapeutic value of inhibiting USP11 to sensitize gastric cancer to chemotherapy.
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http://dx.doi.org/10.1016/j.clinre.2021.101779DOI Listing
July 2021

Identification of the Hub Genes in Alzheimer's Disease.

Comput Math Methods Med 2021 15;2021:6329041. Epub 2021 Jul 15.

Department of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, 170 Xinsong Road, 201199 Shanghai, China.

Purpose: Alzheimer's disease (AD) is considered to be the most common neurodegenerative disease and also one of the major fatal diseases affecting the elderly, thus bringing a huge burden to society. Therefore, identifying AD-related hub genes is extremely important for developing novel strategies against AD.

Materials And Methods: Here, we extracted the gene expression profile GSE63061 from the National Center for Biotechnology Information (NCBI) GEO database. Once the unverified gene chip was removed, we standardized the microarray data after quality control. We utilized the Limma software package to screen the differentially expressed genes (DEGs). We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEGs. Subsequently, we constructed a protein-protein interaction (PPI) network using the STRING database.

Result: We screened 2169 DEGs, comprising 1313 DEGs with upregulation and 856 DEGs with downregulation. Functional enrichment analysis showed that the response of immune, the degranulation of neutrophils, lysosome, and the differentiation of osteoclast were greatly enriched in DEGs with upregulation; peptide biosynthetic process, translation, ribosome, and oxidative phosphorylation were dramatically enriched in DEGs with downregulation. 379 nodes and 1149 PPI edges were demonstrated in the PPI network constructed by upregulated DEGs; 202 nodes and 1963 PPI edges were shown in the PPI network constructed by downregulated DEGs. Four hub genes, including GAPDH, RHOA, RPS29, and RPS27A, were identified to be the newly produced candidates involved in AD pathology.

Conclusion: GAPDH, RHOA, RPS29, and RPS27A are expected to be key candidates for AD progression. The results of this study can provide comprehensive insight into understanding AD's pathogenesis and potential new therapeutic targets.
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http://dx.doi.org/10.1155/2021/6329041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302378PMC
July 2021

A residual network with attention module for hyperspectral information of recognition to trace the origin of rice.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 15;263:120155. Epub 2021 Jul 15.

School of Automation Engineering, Northeast Electric Power University, Jilin 132012, China. Electronic address:

In this work, a neural network framework for hyperspectral information recognition was proposed, combined with residual block and convolutional block attention module (CBAM) to enhance the detection performance of hyperspectral for tracing the rice quality. Firstly, the hyperspectral image system was used to obtain the hyperspectral information of the rice. Secondly, due to the small data set, the structure of the residual network was designed based on the characteristics of the hyperspectral information to prevent overfitting the model. Finally, the CBAM was introduced to calculate the channel and spatial attention to redistribute the weight parameter and enhance the classification performance of the model. The results showed that our (Res-CBAM) model had better classification performance than other classification methods. The classification accuracy of the rice was 96.33%. This study provided a strategy to enhance the detection performance of hyperspectral, and an intelligent technology to trace the rice quality.
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http://dx.doi.org/10.1016/j.saa.2021.120155DOI Listing
July 2021

IL-1β-induced Elevation of SLC7A11 Promotes Hepatocellular Carcinoma Metastasis through Upregulating PD-L1 and CSF1.

Hepatology 2021 Jul 20. Epub 2021 Jul 20.

Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.

Background & Aims: Due to paucity of effective treatment options, metastasis is still a major cause for hepatocellular carcinoma (HCC)-associated mortality. Molecular mechanism of inflammation-induced HCC metastasis is largely unknown. Here, we characterized the function of solute carrier family 7 member 11 (SLC7A11) in inflammation-related HCC metastasis and probed therapy strategies for this subpopulation patients.

Approach & Results: Elevated expression of SLC7A11 was positively correlated with poor tumor differentiation, and higher tumor-nodule-metastasis (TNM) stage, and indicated poor prognosis in human HCC. SLC7A11 increased HIF1α expression through reducing α-ketoglutarate (αKG) level via exporting glutamate. SLC7A11 upregulated programmed death-1-ligand 1 (PD-L1) and colony stimulating factor-1 (CSF1) expression through αKG-HIF1α cascade. SLC7A11 overexpression in HCC cells promoted intratumoral tumour-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) infiltration through CSF1/CSF1R axis, whereas knockdown of CSF1 attenuated SLC7A11-mediated intratumoral TAMs and MDSCs infiltration and HCC metastasis. Depletion of either TAMs or MDSCs decreased SLC7A11-mediated HCC metastasis. Furthermore, combination of CSF1R inhibitor BZL945 and anti-PD-L1 antibody blocked SLC7A11-induced HCC metastasis. In addition, interleukin 1β (IL-1β) upregulated SLC7A11 expression through the IL-1R1/ERK/SP1 pathway. SLC7A11 knockdown impaired IL-1β-promoted HCC metastasis. Anakinra, an IL-1R1 antagonist, reversed IL-1β-promoted HCC metastasis. In human HCC tissues, SLC7A11 expression was positively associated with HIF1α, PD-L1, and CSF1 expression, and intratumoral TAMs and MDSCs infiltration.

Conclusions: IL-1β-induced SLC7A11 overexpression upregulated PD-L1 and CSF1 through αKG/HIF1α axis, which promoted TAMs and MDSCs infiltration. Interruption of this oncogenic loop may provide a promising therapy strategy for the inhibition of SLC7A11-mediated HCC metastasis.
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http://dx.doi.org/10.1002/hep.32062DOI Listing
July 2021

Left ventricular diastolic pressure gradient and outcome in advanced chronic kidney disease patients with preserved ejection fraction.

Int J Cardiovasc Imaging 2021 Jul 20. Epub 2021 Jul 20.

Department of Cardiology, West China Hospital of Sichuan University, 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.

Assessment of left ventricular (LV) diastolic dysfunction is important in patients with chronic kidney disease (CKD). The early diastolic peak intraventricular pressure gradient (IVPG) has a vital role in diastolic function. Relative pressure imaging (RPI) is a new echocardiographic method to quantify IVPG. The purpose of this study was to analyze RPI-derived IVPG in advanced CKD patients with preserved LV ejection fraction. The study population consisted of 51 advanced CKD patients and 39 healthy controls. Patients were stratified by the evidence of heart failure with preserved ejection fraction (HFpEF) into HFpEF group (32 patients) and non-HFpEF group (19 patients). RPI analysis was used to determine the early diastolic LV relative pressure and pressure distribution. The total IVPG and segmental IVPGs corresponding to basal, mid, and apical part of the LV were calculated. Total IVPG, along with apical and mid IVPGs were all significantly reduced in HFpEF Group compared with non-HFpEF Group and controls (all P < 0.05). But no significant difference of total or segmental IVPGs was found between non-HFpEF Group and the controls. Additionally, apical IVPG < 0.02 mmHg/cm (Hazard ratio 9.82, 95 % confidence interval 2.01-48.01, P = 0.005) was the independent risk factor for the composite outcome (mortality and cardiovascular hospitalization) during a median follow-up of 24 months. Advanced CKD patients with HFpEF exhibited decreased apical and mid IVPG of the LV, and the severity of apical IVPG reduction correlated with poor outcome.
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http://dx.doi.org/10.1007/s10554-021-02339-4DOI Listing
July 2021

Improved lipid productivity of Scenedesmus obliquus with high nutrient removal efficiency by mixotrophic cultivation in actual municipal wastewater.

Chemosphere 2021 Jul 12;285:131475. Epub 2021 Jul 12.

Zhejiang Provincial Key Laboratory of Petrochemical Pollution Control, School of Petrochemical Engineering & Environment, Zhejiang Ocean University, Zhoushan, 316022, China. Electronic address:

This study was aimed to assess the growth and lipid productivity improvement of a green microalga Scenedesmus obliquus by mixotrophic cultivation, via addition of sodium acetate (NaAc) into actual municipal wastewater (AMW). Moreover, the nutrient removal efficiency of the culture media in terms of carbon, nitrogen, and phosphorus was investigated. The results showed that the S. obliquus grew better in the AMW than in the BG11 medium (0.20 g L vs 0.16 g L in dry cell weight), and the final algal lipid productivity was higher (9.02 mg L d vs 7.75 mg L d, P < 0.05). Further, the addition of NaAc significantly stimulated the algal growth and lipid productivity. Specifically, the highest improvement was obtained by the NaAc-addition of 1 g L, where the algal dry cell weight increased 2.40 times than that in the AMW with little organic carbon (0.48 mg L vs 0.20 mg L, P < 0.01), and the corresponding algal lipid productivity increased 2.44 time (22.08 mg L d vs 9.02 mg L d, P < 0.01). Meanwhile, the addition of 1 g L of NaAc significantly increased the microalga-driven nitrogen and phosphorus removal efficiency, respectively by 1.75 and 2.23 times (82.20% vs 46.85% for total nitrogen, and 76.35% vs 34.18% for total phosphorus). In summary, this study confirmed the feasibility of using organic carbon-supplemented AMW to replace the artificial media for microalgae-based lipid production and nutrient recycling.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131475DOI Listing
July 2021

SUMOylation activates large tumour suppressor 1 to maintain the tissue homeostasis during Hippo signalling.

Oncogene 2021 Jul 15. Epub 2021 Jul 15.

Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, China.

Large tumour suppressor (LATS) 1/2, the core kinases of Hippo signalling, are critical for maintaining tissue homeostasis. Here, we investigate the role of SUMOylation in the regulation of LATS activation. High cell density induces the expression of components of the SUMOylation machinery and enhances the SUMOylation and activation of Lats1 but not Lats2, whereas genetic deletion of the SUMOylation E2 ligase, Ubc9, abolishes this Lats1 activation. Moreover, SUMOylation occurs at the K830 (mouse K829) residue to activate LATS1 and depends on the PIAS1/2 E3 ligase. Whereas the K830 deSUMOylation mutation of LATS1 found in the human metastatic prostate cancers eliminates the kinase activity by attenuating the formation of the phospho-MOB1/phospho-LATS1 complex. As a result, the LATS1(K830R) transgene phenocopies Yap transgene to cause the oversized livers in mice, whereas Lats1(K829R) knock-in phenocopies the deletion of Lats1 in causing the reproductive and endocrine defects and ovary tumours in mice. Thus, SUMOylation-mediated LATS1 activation is an integral component of Hippo signalling in the regulation of tissues homeostasis.
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http://dx.doi.org/10.1038/s41388-021-01937-9DOI Listing
July 2021

Differential Bacteriophage Efficacy in Controlling in Cattle Hide and Soil Models.

Front Microbiol 2021 28;12:657524. Epub 2021 Jun 28.

Department of Animal Science, Texas A&M University, College Station, TX, United States.

Asymptomatic carriage in beef cattle is a food safety concern and the beef feedlot environment and cattle hides are reservoirs of this pathogen. Bacteriophages present an attractive non-antibiotic strategy for control of in beef. In this study, four diverse and genetically unrelated phages, Sergei, Season12, Sw2, and Munch, were characterized and tested alone and in combination for their ability to control in cattle hide and soil systems, which are relevant models for control in beef production. Phage Sergei is a member of the genus , phage Season12 was identified as a member of the genus, Sw2 was identified as a member of the T5-like genus, and Munch was found to be a novel "jumbo" myovirus. Observed pathogen reductions in the model systems ranged from 0.50 to 1.75 log CFU/cm in hides and from 0.53 to 1.38 log CFU/g in soil, with phages Sergei and Sw2 producing greater reductions (∼1 log CFU/cm or CFU/g) than Season12 and Munch. These findings are in accordance with previous observations of phage virulence, suggesting the simple ability of a phage to form plaques on a bacterial strain is not a strong indicator of antimicrobial activity, but performance in liquid culture assays provides a better predictor. The antimicrobial efficacies of phage treatments were found to be phage-specific across model systems, implying that a phage capable of achieving bacterial reduction in one model is more likely to perform well in another. Phage combinations did not produce significantly greater efficacy than single phages even after 24 h in the soil model, and phage-insensitive colonies were not isolated from treated samples, suggesting that the emergence of phage resistance was not a major factor limiting efficacy in this system.
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http://dx.doi.org/10.3389/fmicb.2021.657524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273493PMC
June 2021

Circular RNA circFAT1(e2) Promotes Colorectal Cancer Tumorigenesis via the miR-30e-5p/ITGA6 Axis.

Comput Math Methods Med 2021 26;2021:9980459. Epub 2021 Jun 26.

Department of General Practice, Minhang Hospital, Fudan University, 170 Xinsong Road, 201199 Shanghai, China.

circRNAs (circular RNAs) are a family of noncoding RNAs and have diverse physiological and pathological functions. However, the functions and mechanisms of circRNAs in the development and progression of colorectal cancer (CRC) remain largely unknown. Here, we aimed to explore the functions and roles of circFAT1(e2) in CRC. qRT-PCR revealed that circFAT1(e2) in CRC tumor tissues was upregulated compared with that in adjacent normal tissues and was also upregulated in CRC cell lines. Small interfering RNAs (siRNAs) against circFAT1(e2) were used to decrease the expression of circFAT1(e2) in HCT116 and RKO cells in vitro. The roles of circFAT1(e2) in CRC cell metastasis and proliferation were then determined by transwell and CCK-8 assays. The results showed that circFAT1(e2) silencing markedly suppressed CRC growth. Moreover, we identified circFAT1(e2) as a promoter of CRC metastasis. Knockdown of circFAT1(e2) evidently reduced HCT116 and RKO cell migration and invasion. Furthermore, the regulatory relationship between circFAT1(e2) and its target miRNAs was verified by a luciferase reporter assay. We demonstrated that circFAT1(e2) could sponge miR-30e-5p, which regulated the expression level of integrin 6 (ITGA6), the downstream target gene of miR-30e-5p. Rescue assays demonstrated that knockdown of miR-30e-5p enhanced CRC proliferation and migration via ITGA6. Taken together, our results reveal the novel oncogenic roles of circFAT1(e2) in CRC through the miR-30e-5p/ITGA6 axis.
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http://dx.doi.org/10.1155/2021/9980459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257361PMC
June 2021

Stocking density alters growth performance, serum biochemistry, digestive enzymes, immune response, and muscle quality of largemouth bass (Micropterus salmoides) in in-pond raceway system.

Fish Physiol Biochem 2021 Aug 5;47(4):1243-1255. Epub 2021 Jul 5.

Freshwater Fishery Healthy Breeding Laboratory of Ministry of Agriculture, Zhejiang Institute of Freshwater Fisheries, 999 Hangchaoqiao Road, Huzhou, Zhejiang, 313001, China.

The effects of stocking density on growth performance, serum biochemistry, digestive enzymes, immune response, and muscle quality of largemouth bass (Micropterus salmoides) reared in nine in-pond raceway systems (IPRS, 22.0 m × 5.0 m × 2.0 m) were studied. M. salmoides with initial an body weight of 8.25 ± 0.51 g and body length of 6.99 ± 0.44 cm were reared at an initial stocking density of 90.91 ind./m (low stocking density, LSD), 113.63 ind./m (middle stocking density, MSD), and 136.36 ind./m (high stocking density, HSD) with triplication. After 300 days of culture, MSD recorded the highest final body weight, weight gain, specific growth rate, and yield, but the food conversion ratio in MSD was the lowest. The viscerosomatic index in LSD was significantly higher than other groups. The fish serum reared at HSD showed significantly lower total protein, higher total cholesterol, triglyceride, total bilirubin, glucose content, alanine transaminase, and aspartate transaminase activity. Significantly lower intestinal amylase, lipase, trypsin activities, hepatic superoxide dismutase (SOD) and catalase (CAT) activities, and higher malondialdehyde content were detected in HSD compared to others. The content of crude lipid, saturated fatty acid decreased, and total essential amino acid, delicious amino acid, and polyunsaturated fatty acid increased in muscle with stocking density increase. No significant difference was observed in muscle texture. Profitability analysis indicated the benefit-to-cost ratio varied between 1.10 and 1.68, of which MSD was significantly higher than others. The optimal stocking density for M. salmoides should be 113.63 ind./m in an IPRS farm.
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http://dx.doi.org/10.1007/s10695-021-00948-3DOI Listing
August 2021

SKP-SCs transplantation alleviates 6-OHDA-induced dopaminergic neuronal injury by modulating autophagy.

Cell Death Dis 2021 Jul 5;12(7):674. Epub 2021 Jul 5.

Department of Neurology, Affiliated Hospital of Nantong University, Nantong, China.

Parkinson's disease is a common neurodegenerative disease. Cell transplantation is a promising therapeutic option for improving the survival and function of dopaminergic neurons, but the mechanisms underlying the interaction between the transplanted cells and the recipient neurons remain to be studied. In this study, we investigated the effects of skin precursor cell-derived Schwann cells (SKP-SCs) directly cocultured with 6-OHDA-injured dopaminergic neurons in vitro and of SKP-SCs transplanted into the brains of 6-OHDA-induced PD mice in vivo. In vitro and in vivo studies revealed that SKP-SCs could reduce the damage to dopaminergic neurons by enhancing self-autophagy and modulating neuronal autophagy. Thus, the present study provides the first evidence that cell transplantation mitigates 6-OHDA-induced damage to dopaminergic neurons by enhancing self-autophagy, suggesting that earlier transplantation of Schwann cells might help alleviate the loss of dopaminergic neurons.
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http://dx.doi.org/10.1038/s41419-021-03967-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257782PMC
July 2021

[Effects of experimental warming on soil nitrogen transformation in alpine scrubland of eastern Qinghai-Tibet Plateau, China].

Ying Yong Sheng Tai Xue Bao 2021 Jun;32(6):2045-2052

College of Life Science, China West Normal University, Nanchong 637009, Sichuan, China.

We investigated the effects of warming on soil nitrogen cycling process in alpine scrub ecosystem, with an simulated warming experiment at alpine scrubland on the eastern Qinghai-Tibet Plateau, China. We examined the responses of soil nitrogen transformation rate to warming in three critical periods (the early, late, and non-growing seasons). The results showed that warming increased soil temperature by 1.2 ℃, but decreased soil moisture by 2.5%. The soil net nitrogen mineralization rates (, ammonification and nitrification) in the growing season were significantly higher than those in the non-growing season. The rates of soil net nitrogen fixation in the non-growing season were significantly higher than that in the growing season. Soil nitrification was the major process of soil nitrogen transformation in the early growing season, while soil ammonification was the major one in the late growing season and non-growing season. The effects of experimental warming on soil nitrogen transformation differed among those three periods. Experimental warming significantly increased soil net ammonification, nitrification, nitrogen mine-ralization and fixation in the early growing season, and enhanced soil net nitrification and nitrogen mineralization in the non-growing season. However, warming significantly decreased soil net nitrification, nitrogen mineralization and fixation in the late growing season and soil net ammonification in the non-growing season. Moreover, warming did not affect soil net nitrogen fixation rates in the non-growing season and soil net nitrification rates in the late growing season. Future climate warming would significantly change soil nitrogen transformation by accelerating soil nitrogen cycling in the alpine scrub ecosystem on the eastern Qinghai-Tibet Plateau.
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http://dx.doi.org/10.13287/j.1001-9332.202106.007DOI Listing
June 2021

Honokiol inhibits proliferation of colorectal cancer cells by targeting Anoctamin 1/TMEM16A Ca -activated Cl channels.

Br J Pharmacol 2021 Jun 30. Epub 2021 Jun 30.

Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.

Background And Purpose: Anoctamin 1 (Ano1, also named TMEM16A) Ca -activated Cl channels contribute to the pathogenesis of colorectal cancer. Honokiol is known to inhibit cell proliferation and tumor growth in colorectal cancer. However, the molecular target of honokiol remains unclear. This study aimed to investigate whether honokiol inhibited cell proliferation of colorectal cancer by targeting Ano1 channels.

Experimental Approach: Patch clamp techniques were performed to study the effect of honokiol on Ca -activated Cl currents in HEK293 cells overexpressing Ano1- or Ano2-containing plasmids or in human colorectal carcinoma SW620 cells. Site-directed mutagenesis was used to identify the critical residues for honokiol-induced Ano1 inhibition. CCK-8 assay measured cell proliferation in SW620 cells or human intestinal epithelial NCM460 cells.

Key Results: Honokiol blocked Ano1 currents in Ano1-overexpressing HEK293 cells and SW620 cells. Honokiol more potently inhibited Ano1 currents than Ano2 currents. Three amino acids (R429, K430, and N435) were critical for honokiol-induced Ano1 inhibition. The R429A/K430L/N435G mutation reduced the sensitivity of Ano1 to honokiol. Honokiol inhibited SW620 cell proliferation, and this effect was reduced by Ano1-shRNAs. Furthermore, Ano1 overexpression promoted proliferation in NCM460 cells with low Ano1 endogenous expression, and resulted in an increased sensitivity to honokiol. Overexpression of the R429A/K430L/N435G mutation reduced WT Ano1-induced increase in the sensitivity of NCM460 cells to honokiol.

Conclusion And Implications: We identified a new anti-cancer mechanism of honokiol, by which honokiol inhibits cell proliferation by targeting Ano1 Ca -activated Cl channels.
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http://dx.doi.org/10.1111/bph.15606DOI Listing
June 2021

Antibiotic Timing and Progression to Septic Shock Among Emergency Department Patients with Suspected Infection.

Chest 2021 Jun 26. Epub 2021 Jun 26.

University of Kansas Medical Center, Department of Internal Medicine, Pulmonary and Critical Care Division, Kansas City, KS, USA. Electronic address:

Background: Recent medical society opinions have questioned the use of early antimicrobials in patients with sepsis, but without septic shock.

Research Question: Is time from Emergency Department (ED) presentation to administration of antibiotics associated with progression to septic shock among patients presenting with suspected infection?

Study Design: and Methods: This was a retrospective cohort study from March 2007 to March 2020. All adults with suspected infection and first antimicrobial administered within 24 hours of triage were included. Patients with shock on presentation were excluded. We performed univariate and multivariate logistic regressions predicting progression to septic shock.

Results: 74,114 patient encounters were included in the study. 5,510 (7.4%) of the patients progressed to septic shock. Of the patients who progressed to septic shock, 88% had received antimicrobials within the first five hours from triage. In the multivariate logistic model, time (hours) to first antimicrobial administration had an OR of 1.03 [95% CI: 1.02-1.04; p<0.001] for progression to septic shock and 1.02 [95% CI: 0.99-1.04; p = 0.121] for in-hospital mortality. When adjusted for severity of illness, each hour delayed until initial antimicrobial administration was associated with a 4.0% increase in progression to septic shock for every hour up to 24 hours from triage. qSOFA positive patients were given antibiotics at an earlier time point than SIRS positive patients (0.82 vs 1.2 hours; p<0.05). However, median time to septic shock was significantly shorter (p<0.05) for qSOFA positive patients at triage (11.2 hours) compared with SIRS positive patients at triage (26 hours).

Interpretation: Delays in first antimicrobial administration in patients with suspected infection are associated with rapid increases in likelihood of progression to septic shock. Additionally, qSOFA has higher specificity than SIRS for predicting septic shock, but is associated with a worse outcome even when patients receive early antibiotics.
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http://dx.doi.org/10.1016/j.chest.2021.06.029DOI Listing
June 2021

Mixotrophic cultivation of microalgae coupled with anaerobic hydrolysis for sustainable treatment of municipal wastewater in a hybrid system of anaerobic membrane bioreactor and membrane photobioreactor.

Bioresour Technol 2021 Oct 24;337:125457. Epub 2021 Jun 24.

Department of Environmental Science and Engineering, School of Petrochemical Engineering & Environment, Zhejiang Ocean University, Zhoushan 316000, China.

This study investigated the possibility of coupling anaerobic hydrolysis in an anaerobic membrane bioreactor (AnMBR) with mixotrophic microalgae cultivation in a membrane photobioreactor (MPBR) for the sustainable treatment of municipal wastewater. Using the hydrolyzed wastewater discharged from AnMBR, Chlorella pyrenoidosa in MPBR grew in a mixotrophic mode and realized rapid growth. During the stable operation, MPBR achieved average carbon capture rate of 42.82 mg L d and algal lipid production rate of 19.66 mg L d. The average reduction in TN, TP, and TOC during stable operation was 96.7%, 98.0%, and 95.9%, respectively. Mass balance analysis showed that the overall system captured 14.76 mg of carbon from the atmosphere per liter of wastewater treated. Therefore, this AnMBR-MPBR hybrid system simultaneously realized advanced treatment of municipal wastewater, efficient production of algal lipid, and carbon capture from atmosphere, and thus has a good potential in the sustainable treatment of municipal wastewater.
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http://dx.doi.org/10.1016/j.biortech.2021.125457DOI Listing
October 2021

Nose-to-brain delivery of borneol modified tanshinone IIA nanoparticles in prevention of cerebral ischemia/reperfusion injury.

Drug Deliv 2021 Dec;28(1):1363-1375

Institute of Interdisciplinary Integrative Medicine Research, Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Targeted treatment of cerebral ischemia/reperfusion injury (CIRI) remains a problem due to the difficulty in drug delivery across the blood-brain barrier (BBB). In this study, we developed Bo-TSA-NP, a novel tanshinone IIA (TSA) loaded nanoparticles modified by borneol, which has long been proved with the ability to enhance other drugs' transport across the BBB. The Bo-TSA-NP, with a particle size of about 160 nm, drug loading of 3.6%, showed sustained release and P-glycoprotein (P-gp) inhibition property. It demonstrated a significantly higher uptake by 16HBE cells through the clathrin/caveolae-mediated endocytosis and micropinocytosis. Following intranasal (IN) administration, Bo-TSA-NP significantly improved the preventive effect on a rat model of CIRI with improved neurological scores, decreased cerebral infarction areas and a reduced content of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) in rat brain. In conclusion, these results indicate that Bo-TSA-NP is a promising nose-to-brain delivery system that can enhance the prevention effect of TSA on CIRI.
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http://dx.doi.org/10.1080/10717544.2021.1943058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245080PMC
December 2021

Molecular epidemiology and drug-resistance of tuberculosis in Luodian revealed by whole genome sequencing.

Infect Genet Evol 2021 Jun 24;93:104979. Epub 2021 Jun 24.

Department of Respiratory Medicine, Affiliated Hospital of Zunyi Medical University, No.149 Dalian Road, Zunyi 563000, Guizhou, China. Electronic address:

In this study, we aimed to investigate the molecular epidemiology and drug-resistance profiles of tuberculosis (TB) in Luodian, an area with highest TB incidence and limited healthcare resources in Guizhou, China. The passive case finding strategy was used to identify suspected pulmonary TB with symptoms, and individuals with positive Mycobacterium tuberculosis (MTB) culture were enrolled from May 22, 2018 to April 21, 2019. All the 107 cases except three came from nine towns, including 55.1% from Longping and Bianyang. The phylogeny tree showed that 53.3% of strains were Lineage 2 (Beijing genotype), while 46.7% were Lineage 4 (Euro-American genotype). Among Lineage 2 strains, 66.7% were of "modern" Beijing type. Seven clusters with genomic distance within 12 SNPs were identified. The clusters included 14 strains, accounting for a clustering rate of 13.1%. The distance separating the clustered cases was between 2.1 and 71.0 km (Km), with an average paired distance of 21.8 Km (interquartile range, 2.8-38.0 Km). Based on the gene mutations associated with drug-resistance, we predicted that 4.8% of strains were resistant to isoniazid, 3.7% to rifampicin, and 3.7% to streptomycin; only one strain (0.9%) had multidrug resistance (MDR). This study found low drug-resistance rates in Luodian, and the sub-lineage of the "modern" Beijing branch has recent expansion in Luodian. This work may also serve as a genomic baseline to assess the evolution and spread of MTB in Guizhou.
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http://dx.doi.org/10.1016/j.meegid.2021.104979DOI Listing
June 2021

Genome-guided investigation of anti-inflammatory sesterterpenoids with 5-15 trans-fused ring system from phytopathogenic fungi.

Appl Microbiol Biotechnol 2021 Jul 22;105(13):5407-5417. Epub 2021 Jun 22.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Fungal terpenoids catalyzed by bifunctional terpene synthases (BFTSs) possess interesting bioactive and chemical properties. In this study, an integrated approach of genome mining, heterologous expression, and in vitro enzymatic activity assay was used, and these identified a unique BFTS sub-clade critical to the formation of a 5-15 trans-fused bicyclic sesterterpene preterpestacin I (1). The 5-15 bicyclic BFTS gene clusters were highly conserved but showed relatively wide phylogenetic distribution across several species of the diverged fungal classes Dothideomycetes and Sordariomycetes. Further genomic organization analysis of these homologous biosynthetic gene clusters from this clade revealed a glycosyltransferase from the graminaceous pathogen Bipolaris sorokiniana isolate BS11134, which was absent in other 5-15 bicyclic BFTS gene clusters. Targeted isolation guided by BFTS gene deletion led to the identification of two new sesterterpenoids (4, and 6) from BS11134. Compounds 2 and 4 showed moderate effects on LPS-induced nitrous oxide production in the murine macrophage-like cell line RAW264.7 with in vitro inhibition rates of 36.6 ± 2.4% and 24.9 ± 2.1% at 10 μM, respectively. The plausible biosynthetic pathway of these identified compounds was proposed as well. This work revealed that phytopathogenic fungi can serve as important sources of active terpenoids via systematic analysis of the genomic organization of BFTS biosynthetic gene clusters, their phylogenetic distribution in fungi, and cyclization properties of their metabolic products. KEY POINTS: • Genome mining of the first BFTS BGC harboring a glycosyltransferase. • Gene-deletion guided isolation revealed three novel 5-15 bicyclic sesterterpenoids. • Biosynthetic pathway of isolated sesterterpenoids was proposed.
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http://dx.doi.org/10.1007/s00253-021-11192-3DOI Listing
July 2021

Robust k-WTA Network Generation, Analysis, and Applications to Multiagent Coordination.

IEEE Trans Cybern 2021 Jun 16;PP. Epub 2021 Jun 16.

In this article, a robust k-winner-take-all (k-WTA) neural network employing the saturation-allowed activation functions is designed and investigated to perform a k-WTA operation, and is shown to possess enhanced robustness to disturbance compared to existing k-WTA neural networks. Global convergence and robustness of the proposed k-WTA neural network are demonstrated through analysis and simulations. An application studied in detail is competitive multiagent coordination and dynamic task allocation, in which k active agents [among m (m > k)] are allocated to execute a tracking task with the static m-k ones. This is implemented by adopting a distributed k-WTA network with limited communication, aided with a consensus filter. Simulation results demonstrating the system's efficacy and feasibility are presented.
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http://dx.doi.org/10.1109/TCYB.2021.3079457DOI Listing
June 2021

Natural biomaterial sarcosine as an interfacial layer enables inverted organic solar cells to exhibit over 16.4% efficiency.

Nanoscale 2021 Jul 16;13(25):11128-11137. Epub 2021 Jun 16.

Collaborative Innovation Center of Light Manipulations and Applications in Universities of Shandong, School of Physics and Electronics, Shandong Normal University, Jinan 250014, China.

The natural biomaterial sarcosine as an electron transport layer (ETL) to modify ITO or ITO/ZnO was successfully introduced into inverted organic solar cells (OSCs) with PM6:BTP-BO-4Cl as the active layer. The introduction of sarcosine on the surface of ITO or ITO/ZnO resulted in lower work function (WF) and higher surface energy. The active layers processed on the surfaces of ITO or ITO/ZnO presented a more optimized morphology and a more ordered molecular arrangement after their modification with sarcosine. The introduction of sarcosine as an ETL promoted charge transport and collection in the OSCs. Therefore, the power conversion efficiency (PCE) of the OSCs increased to 13.53% from 3.86% by modifying ITO with sarcosine. The PCE of the OSCs with ZnO as ETLs improved to 16.45% from 14.85% by modifying ZnO with sarcosine. The improved PCEs benefited from the simultaneously improved short-circuit current density (J), fill factor (FF), and open-circuit voltage (V). Therefore, this work demonstrates that sarcosine has great potential as an ETL to improve the performance of OSCs.
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http://dx.doi.org/10.1039/d0nr09090eDOI Listing
July 2021

Downregulation of decidual SKP2 is associated with human recurrent miscarriage.

Reprod Biol Endocrinol 2021 Jun 11;19(1):88. Epub 2021 Jun 11.

Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200135, China.

Background: Recurrent miscarriage (RM) is a very frustrating problem for both couples and clinicians. To date, the etiology of RM remains poorly understood. Decidualization plays a critical role in implantation and the maintenance of pregnancy, and its deficiency is closely correlated with RM. The F-box protein S-phase kinase associated protein 2 (SKP2) is a key component of the SCF-type E3 ubiquitin ligase complex, which is critically involved in ErbB family-induced Akt ubiquitination, aerobic glycolysis and tumorigenesis. SKP2 is pivotal for reproduction, and SKP2-deficient mice show impaired ovarian development and reduced fertility.

Methods: Here, we investigated the expression and function of SKP2 in human decidualization and its relation with RM. A total of 40 decidual samples were collected. Quantitative PCR analysis, western blot analysis and immunohistochemistry analysis were performed to analyze the differential expression of SKP2 between RM and control cells. For in vitro induction of decidualization, both HESCs (human endometrial stromal cells) cell line and primary ESCs (endometrial stromal cells) were used to analyze the effects of SKP2 on decidualization via siRNA transfection.

Results: Compared to normal pregnant women, the expression of SKP2 was reduced in the decidual tissues from individuals with RM. After in vitro induction of decidualization, knockdown of SKP2 apparently attenuated the decidualization of HESCs and resulted in the downregulation of HOXA10 and FOXM1, which are essential for normal human decidualization. Moreover, our experiments demonstrated that SKP2 silencing reduced the expression of its downstream target GLUT1.

Conclusions: Our study indicates a functional role of SKP2 in RM: downregulation of SKP2 in RM leads to impaired decidualization and downregulation of GLUT1 and consequently predisposes individuals to RM.
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http://dx.doi.org/10.1186/s12958-021-00775-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194034PMC
June 2021

Novel deep learning-based transcriptome data analysis for drug-drug interaction prediction with an application in diabetes.

BMC Bioinformatics 2021 Jun 11;22(1):318. Epub 2021 Jun 11.

Big Data Decision Institute, Jinan University, Guangzhou, 510632, China.

Background: Drug-drug interaction (DDI) is a serious public health issue. The L1000 database of the LINCS project has collected millions of genome-wide expressions induced by 20,000 small molecular compounds on 72 cell lines. Whether this unified and comprehensive transcriptome data resource can be used to build a better DDI prediction model is still unclear. Therefore, we developed and validated a novel deep learning model for predicting DDI using 89,970 known DDIs extracted from the DrugBank database (version 5.1.4).

Results: The proposed model consists of a graph convolutional autoencoder network (GCAN) for embedding drug-induced transcriptome data from the L1000 database of the LINCS project; and a long short-term memory (LSTM) for DDI prediction. Comparative evaluation of various machine learning methods demonstrated the superior performance of our proposed model for DDI prediction. Many of our predicted DDIs were revealed in the latest DrugBank database (version 5.1.7). In the case study, we predicted drugs interacting with sulfonylureas to cause hypoglycemia and drugs interacting with metformin to cause lactic acidosis, and showed both to induce effects on the proteins involved in the metabolic mechanism in vivo.

Conclusions: The proposed deep learning model can accelerate the discovery of new DDIs. It can support future clinical research for safer and more effective drug co-prescription.
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http://dx.doi.org/10.1186/s12859-021-04241-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194123PMC
June 2021

Nested Case-Control Study of Corin Combined with sFlt-1/PLGF in Predicting the Risk of Preeclampsia.

Int J Gen Med 2021 3;14:2313-2320. Epub 2021 Jun 3.

Postgraduate Department, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong.

Background: Preeclampsia (PE), a serious pregnancy disorder, is responsible for maternal and fetal mortality worldwide. At present, numerous candidate biomarkers have been studied to predict PE.

Objective: To explore the role of Corin in PE risk prediction and then evaluate the predictive ability of soluble vascular endothelial growth factor receptor-1 (sFlt-1), placenta growth factor (PLGF), and sFlt-1/PLGF after the addition of Corin.

Methods: A total of 135 pregnant women from Affiliated Hospital of Shandong University of Traditional Chinese Medicine participated in this study in their first trimester. A nested case-control study was conducted and all subjects were divided into PE groups (n=46) and controls (n=89). The levels of PLGF, sFlt-1, sFlt-1/PLGF ratio, and Corin of the two groups at 12-16 weeks of gestation were measured and analyzed. Receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to evaluate the predictive ability of various biomarkers.

Results: The concentrations of sFlt-1, sFlt-1/PLGF, and Corin in PE group were significantly higher than that in controls, while the concentration of PLGF in the PE group was lower. The area under curve (AUC) of sFlt-1, PLGF and sFlt-1/PLGF for predicting PE was 0.786, 0.719 and 0.866, respectively. Combined with Corin, the prediction ability of the above biomarkers could be improved to 0.876, 0.847, and 0.897, respectively. Corin in combination with sFlt-1/PLGF resulted in improvements with 12.6% being reclassified and a resulting NRI of 0.142 (0.020~0.263) and IDI of 0.087 (0.037~0.137).

Conclusion: The addition of Corin to sFlt-1, PLGF and sFlt-1/PLGF can improve the ability of each marker to predict PE risk. Corin in combination with sFlt-1/PLGF can be used as ideal markers to identify the pregnant women who subsequently develop PE, which will help in risk stratification and better therapeutic management.
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http://dx.doi.org/10.2147/IJGM.S297344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184237PMC
June 2021

Prognostic and predictive significance of the tumor microenvironment in hepatocellular carcinoma.

Cancer Biomark 2021 May 28. Epub 2021 May 28.

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Identification of molecular markers that reflect the characteristics of the tumor microenvironment (TME) may be beneficial to predict the prognosis of post-operative hepatocellular carcinoma (HCC) patients.

Objective And Methods: A total of 100 tissue samples from HCC patients were separately stained by immunohistochemistry to examine the expression levels of CD56, CD8α, CD68, FoxP3, CD31 and pan-Keratin. The prognostic values were analyzed by Cox regression and the Kaplan-Meier method.

Results: Univariate and multivariate logistic analysis showed that FoxP3 was the independent factor associated with microvascular invasion (MVI), tumor size and envelop invasion; CD68 was associated with envelope invasion and AFP. Kaplan-Meier survival curves revealed that CD68 and FoxP3 expression were significantly associated with relapse free survival (RFS) of HCC patients (P< 0.05). The ROC curve indicated that the combination of tumor number, MVI present and CD68 expression yielded a ROC curve area of 82.3% (86.36% specificity, 68.75% sensitivity) to evaluate the prognosis of HCC patients, which was higher than the classifier established by the combination of tumor number and MVI (78.8% probability, 63.64% specificity and 85.42% sensitivity).

Conclusions: Our study indicated that CD68 and FoxP3 are associated with prognosis of HCC patients, and CD68 can be considered as a potential prognostic and predictive biomarker.
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http://dx.doi.org/10.3233/CBM-203003DOI Listing
May 2021

Detection of copy number variants in African goats using whole genome sequence data.

BMC Genomics 2021 May 29;22(1):398. Epub 2021 May 29.

University of Natural Resources and Life Sciences, Vienna, Austria.

Background: Copy number variations (CNV) are a significant source of variation in the genome and are therefore essential to the understanding of genetic characterization. The aim of this study was to develop a fine-scaled copy number variation map for African goats. We used sequence data from multiple breeds and from multiple African countries.

Results: A total of 253,553 CNV (244,876 deletions and 8677 duplications) were identified, corresponding to an overall average of 1393 CNV per animal. The mean CNV length was 3.3 kb, with a median of 1.3 kb. There was substantial differentiation between the populations for some CNV, suggestive of the effect of population-specific selective pressures. A total of 6231 global CNV regions (CNVR) were found across all animals, representing 59.2 Mb (2.4%) of the goat genome. About 1.6% of the CNVR were present in all 34 breeds and 28.7% were present in all 5 geographical areas across Africa, where animals had been sampled. The CNVR had genes that were highly enriched in important biological functions, molecular functions, and cellular components including retrograde endocannabinoid signaling, glutamatergic synapse and circadian entrainment.

Conclusions: This study presents the first fine CNV map of African goat based on WGS data and adds to the growing body of knowledge on the genetic characterization of goats.
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http://dx.doi.org/10.1186/s12864-021-07703-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164248PMC
May 2021

Complete Genome Sequence of Klebsiella pneumoniae Podophage Pone.

Microbiol Resour Announc 2021 May 27;10(21):e0140520. Epub 2021 May 27.

Center for Phage Technology, Texas A&M University, College Station, Texas, USA.

Klebsiella pneumoniae is a Gram-negative pathogen that has become increasingly antibiotic resistant. Phage therapy is potentially a useful approach to controlling this pathogen. Here, we present the genome sequence of the phiKMV-like K. pneumoniae podophage Pone.
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http://dx.doi.org/10.1128/MRA.01405-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201637PMC
May 2021

Clinical Reasoning: A 65-Year-Old Woman With Tremor.

Neurology 2021 May 26. Epub 2021 May 26.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, China

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http://dx.doi.org/10.1212/WNL.0000000000012262DOI Listing
May 2021

EZH2-mediated inhibition of KLF14 expression promotes HSCs activation and liver fibrosis by downregulating PPARγ.

Cell Prolif 2021 Jul 24;54(7):e13072. Epub 2021 May 24.

Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objectives: Induction of deactivation and apoptosis of hepatic stellate cells (HSCs) are principal therapeutic strategies for liver fibrosis. Krüppel-like factor 14 (KLF14) regulates various biological processes, however, roles, mechanisms and implications of KLF14 in liver fibrosis are unknown.

Materials And Methods: KLF14 expression was detected in human, rat and mouse fibrotic models, and its effects on HSCs were assessed. Chromatin immunoprecipitation assays were utilized to investigate the binding of KLF14 to peroxisome proliferator-activated receptor γ (PPARγ) promoter, and the binding of enhancer of zeste homolog 2 (EZH2) to KLF14 promoter. In vivo, KLF14-overexpressing adenovirus was injected via tail vein to thioacetamide (TAA)-treated rats to investigate the role of KLF14 in liver fibrosis progression. EZH2 inhibitor EPZ-6438 was utilized to treat TAA-induced rat liver fibrosis.

Results: KLF14 expression was remarkably decreased in human, rat and mouse fibrotic liver tissues. Overexpression of KLF14 increased LD accumulation, inhibited HSCs activation, proliferation, migration and induced G2/M arrest and apoptosis. Mechanistically, KLF14 transactivated PPARγ promoter activity. Inhibition of PPARγ blocked the suppressive role of KLF14 overexpression in HSCs. Downregulation of KLF14 in activated HSCs was mediated by EZH2-regulated histone H3 lysine 27 trimethylation. Adenovirus-mediated KLF14 overexpression ameliorated TAA-induced rat liver fibrosis in PPARγ-dependent manner. Furthermore, EPZ-6438 dramatically alleviated TAA-induced rat liver fibrosis. Importantly, KLF14 expression was decreased in human with liver fibrosis, which was significantly correlated with EZH2 upregulation and PPARγ downregulation.

Conclusions: KLF14 exerts a critical anti-fibrotic role in liver fibrosis, and targeting the EZH2/KLF14/PPARγ axis might be a novel therapeutic strategy for liver fibrosis.
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http://dx.doi.org/10.1111/cpr.13072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249795PMC
July 2021
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