Publications by authors named "Ruijie Liu"

112 Publications

Distinctive gene expression patterns and imprinting signatures revealed in reciprocal crosses between cattle sub-species.

BMC Genomics 2021 Jun 3;22(1):410. Epub 2021 Jun 3.

Davies Research Centre, School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, Australia.

Background: There are two genetically distinct subspecies of cattle, Bos taurus taurus and Bos taurus indicus, which arose from independent domestication events. The two types of cattle show substantial phenotypic differences, some of which emerge during fetal development and are reflected in birth outcomes, including birth weight. We explored gene expression profiles in the placenta and four fetal tissues at mid-gestation from one taurine (Bos taurus taurus; Angus) and one indicine (Bos taurus indicus; Brahman) breed and their reciprocal crosses.

Results: In total 120 samples were analysed from a pure taurine breed, an indicine breed and their reciprocal cross fetuses, which identified 6456 differentially expressed genes (DEGs) between the two pure breeds in at least one fetal tissue of which 110 genes were differentially expressed in all five tissues examined. DEGs shared across tissues were enriched for pathways related to immune and stress response functions. Only the liver had a substantial number of DEGs when reciprocal crossed were compared among which 310 DEGs were found to be in common with DEGs identified between purebred livers; these DEGs were significantly enriched for metabolic process GO terms. Analysis of DEGs across purebred and crossbred tissues suggested an additive expression pattern for most genes, where both paternal and maternal alleles contributed to variation in gene expression levels. However, expression of 5% of DEGs in each tissue was consistent with parent of origin effects, with both paternal and maternal dominance effects identified.

Conclusions: These data identify candidate genes potentially driving the tissue-specific differences between these taurine and indicine breeds and provide a biological insight into parental genome effects underlying phenotypic differences in bovine fetal development.
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http://dx.doi.org/10.1186/s12864-021-07667-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176687PMC
June 2021

Complex functionality of protein phosphatase 1 isoforms in the heart.

Authors:
Ruijie Liu

Cell Signal 2021 May 29;85:110059. Epub 2021 May 29.

Department of Biomedical Sciences, Grand Valley State University, Allendale, MI 49401, USA. Electronic address:

Protein phosphatase 1(PP1) is a key regulator of cardiac function through dephosphorylating serine/threonine residues within target proteins to oppose the function of protein kinases. Studies from failing hearts of animal models and human patients have demonstrated significant increase of PP1 activity in myocardium, while elevated PP1 activity in transgenic mice leads to cardiac dysfunction, suggesting that PP1 might be a therapeutic target to ameliorate cardiac dysfunction in failing hearts. In fact, cardiac overexpression of inhibitor 1, the endogenous inhibitor of PP1, increases cardiac contractility and suppresses heart failure progression. However, this notion of PP1 inhibition for heart failure treatment has been challenged by recent studies on the isoform-specific roles of PP1 in the heart. PP1 is a holoenzyme composed of catalytic subunits (PP1α, PP1β, or PP1γ) and regulatory proteins that target them to distinct subcellular locations for functional specificity. This review will summarize how PP1 regulates phosphorylation of some of the key cardiac proteins involved in Ca handling and cardiac contraction, and the potential role of PP1 isoforms in controlling cardiac physiology and pathophysiology.
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http://dx.doi.org/10.1016/j.cellsig.2021.110059DOI Listing
May 2021

The relationship between flavor formation, lipid metabolism, and microorganisms in fermented fish products.

Food Funct 2021 May 25. Epub 2021 May 25.

National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China.

Traditional fermented fish products are favored due to their unique flavors. The fermentation process of fish is accompanied by the formation of flavor substances through a complex metabolic reaction of microorganisms, especially lipolysis and lipid oxidation. However, it is difficult to precisely control the reaction of microorganisms during the fermentation process in modern industrial production, and fermented fish products have lost their traditional characteristic flavors. The purpose of this review is to summarize the different kinds of fermented fish, core microorganisms in it, and flavor formation mechanisms, providing guidance for industrial cultural starters. Future research on the flavor formation mechanism is necessary to confirm the relationship between flavor formation, lipid metabolism, and microorganisms to ensure stable flavor and safety, and to elucidate the mechanism directly toward industrial application.
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http://dx.doi.org/10.1039/d1fo00692dDOI Listing
May 2021

Identification of VWF as a Novel Biomarker in Lung Adenocarcinoma by Comprehensive Analysis.

Front Oncol 2021 22;11:639600. Epub 2021 Apr 22.

NHC Key Laboratory of Cancer Proteomics, Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.

Lung adenocarcinoma (LUAD) is one of the most malignant tumors with high morbidity and mortality worldwide due to the lack of reliable methods for early diagnosis and effective treatment. It's imperative to study the mechanism of its development and explore new biomarkers for early detection of LUAD. In this study, the Gene Expression Omnibus (GEO) dataset GSE43458 and The Cancer Genome Atlas (TCGA) were used to explore the differential co-expressed genes between LUAD and normal samples. Three hundred sixity-six co-expressed genes were identified by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) method. Those genes were mainly enriched in ameboidal-type cell migration (biological process), collagen-containing extracellular matrix (cell component), and extracellular matrix structure constituent (molecular function). The protein-protein network (PPI) was constructed and 10 hub genes were identified, including IL6, VWF, CDH5, PECAM1, EDN1, BDNF, CAV1, SPP1, TEK, and SELE. The expression level of hub genes was validated in the GEPIA database, compared with normal tissues, VWF is lowly expressed and SPP1 is upregulated in LUAD tissues. The survival analysis showed increased expression of SPP1 indicated unfavorable prognosis whereas high expression of VWF suggested favorable prognosis in LUAD (p < 0.05). Based on the immune infiltration analysis, the relationship between SPP1 and VWF expression and macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. Quantitative real-time PCR (qRT-PCR) and western blotting were used to validate the expression of VWF and SPP1 in normal human bronchial epithelial (HBE) cell and three LUAD cell lines, H1299, H1975, and A549. Immunohistochemistry (IHC) was further performed to detect the expression of VWF in 10 cases LUAD samples and matched normal tissues. In summary, the data suggest that VWF is a potential novel biomarker for prognosis of LUAD.
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http://dx.doi.org/10.3389/fonc.2021.639600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100660PMC
April 2021

Interactions between α-tocopherol and γ-oryzanol in oil-in-water emulsions.

Food Chem 2021 Sep 22;356:129648. Epub 2021 Mar 22.

National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, PR China.

The interaction between antioxidants is affected by many factors, such as concentration, ratio and system. In this study, different concentrations of α-tocopherol and γ-oryzanol showed antagonistic effect in the oil-in-water emulsion, and the distribution of α-tocopherol increased in aqueous phase after combined with γ-oryzanol. The concentration could affect the degree of antagonism. According to fluorescence quenching, cyclic voltammetry measurements and the oxidative decomposition of antioxidants during storage, the inhibitory effect of γ-oryzanol on the regeneration of α-tocopherol was proposed to be responsible for the antagonism. This work can provide suggestions for studying the mechanism of antioxidant interaction in emulsion system.
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http://dx.doi.org/10.1016/j.foodchem.2021.129648DOI Listing
September 2021

IRGM promotes melanoma cell survival through autophagy and is a promising prognostic biomarker for clinical application.

Mol Ther Oncolytics 2021 Mar 19;20:187-198. Epub 2020 Dec 19.

Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

Previously, we showed that mouse immunity-related guanosine triphosphatase (GTPase) family M protein 1 (Irgm1) promotes malignant melanoma progression by inducing cellular autophagy flux and metastasis. Human IRGM, a truncated protein functionally distinct from its mouse counterpart, has several splice isoforms. In this study, we analyzed the association of IRGM and human melanoma clinical prognosis and investigated the function of IRGM in human melanoma cells. Data from the training cohort (n = 144) showed that overexpression of IRGM is proportional to melanoma genesis and clinical stages in human tissue chips. A validation cohort (n = 78) further confirmed that IRGM is an independent risk factor promoting melanoma progression and is associated with poor survival of patients. Among IRGM isoforms, we found that IRGMb is responsible for such correlation. In addition, IRGM promoted melanoma cell survival through autophagy, both and . We further showed that the blockade of translocation of high-mobility group box 1 (HMGB1) from the nucleus to cytoplasm inhibits IRGM1-mediated cellular autophagy and reduces cell survival. IRGM functions as a positive regulator of melanoma progression through autophagy and may serve as a promising prognostic marker and therapeutic target.
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http://dx.doi.org/10.1016/j.omto.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889451PMC
March 2021

Circ_0082182 promotes oncogenesis and metastasis of colorectal cancer in vitro and in vivo by sponging miR-411 and miR-1205 to activate the Wnt/β-catenin pathway.

World J Surg Oncol 2021 Feb 17;19(1):51. Epub 2021 Feb 17.

Department of Anorectal Surgery, Jingmen No.1 People's Hospital, No.167, Xiangshan Avenue, Dadao District, Jingmen, 448000, Hubei, China.

Background: Circular RNAs (circRNAs) are a class of endogenous single-strand RNA transcripts with crucial regulation in human cancers. The objective of this study is to investigate the role of circ_0082182 in CRC and its specific functional mechanism.

Methods: The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the levels of circ_0082182, microRNA-411 (miR-411) and microRNA-1205 (miR-1205). Cell proliferation was detected by Cell counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used for determining cell cycle and cell apoptosis. Cell apoptosis was also assessed by caspase3 and caspase9 activities. Cell migration and invasion were examined using scratch assay and transwell assay. The interaction between circ_0082182 and miRNA was validated by the dual-luciferase reporter and biotinylated RNA pull-down assays. Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by Western blot. Xenograft model was established for the research of circ_0082182 in vivo.

Results: Circ_0082182 was upregulated in CRC and could predict the poor prognosis of CRC patients. Functionally, circ_0082182 promoted CRC cell proliferation, cell cycle progression, and metastasis while inhibited apoptosis. Subsequently, circ_0082182 was shown to act as the sponges of miR-411 and miR-1205. MiR-411 and miR-1205 were identified as tumor inhibitors in CRC. Furthermore, circ_0082182 promoted the CRC progression via sponging miR-411 and miR-1205. Moreover, circ_0082182 facilitated the Wnt/β-catenin pathway and EMT process by targeting miR-411 and miR-1205. In vivo, circ_0082182 accelerated the CRC tumorigenesis and EMT process by activating the Wnt/β-catenin pathway by downregulating the expression of miR-411 or miR-1205.

Conclusion: This study showed that circ_0082182 functioned as an oncogene in the developing process of CRC by sponging miR-411 or miR-1205 to activate the Wnt/β-catenin pathway. Circ_0082182 might be a molecular target in the diagnosis and treatment of CRC.
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http://dx.doi.org/10.1186/s12957-021-02164-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891146PMC
February 2021

New perspective toward nutritional support for malnourished cancer patients: Role of lipids.

Compr Rev Food Sci Food Saf 2021 Mar 2;20(2):1381-1421. Epub 2021 Feb 2.

National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China.

To improve the difficulties related to malnutrition, nutritional support has become an essential part of multidisciplinary comprehensive treatment for cancer. Lipids are essential nutrient source for the human body, and nowadays in clinical practices, it has a positive interventional effect on patients suffering from cancer. However, contribution of lipids in nutritional support of cancer patients is still poorly understood. Moreover, the sensory and physicochemical properties of lipids can severely restrict their applications in lipid-rich formula foods. In this review article, for the first time, we have presented a summary of the existing studies which were related to the associations between different lipids and improved malnutrition in cancer patients and discussed possible mechanisms. Subsequently, we discussed the challenges and effective solutions during processing of lipids into formula foods. Further, by considering existing problems in current lipid nutritional support, we proposed a novel method for the treatment of malnutrition, including developing individualized lipid nutrition for different patients depending on the individual's genotype and enterotype. Nonetheless, this review study provides a new direction for future research on nutritional support and the development of lipid-rich formula foods for cancer patients, and probably will help to improve the efficacy of lipids in the treatment of cancer malnutrition.
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http://dx.doi.org/10.1111/1541-4337.12706DOI Listing
March 2021

GPR120 Agonist GW9508 Ameliorated Cellular Senescence Induced by ox-LDL.

ACS Omega 2020 Dec 8;5(50):32195-32202. Epub 2020 Dec 8.

Department of Cardiology, Dongguan Songshanhu Central Hospital, Dongguan, Guangdong 523326, China.

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial senescence is involved in the pathogenesis of atherosclerosis and many cardiovascular diseases. G-protein-coupled receptor 120 (GPR120), a type of orphan G-protein-coupled receptors (GPRs), plays a vital role in mediating anti-inflammatory and insulin-sensitizing effects. The biological function of GPR120 in vascular endothelial cells is largely unknown. The human aortic endothelial cells (HAECs) were treated with ox-LDL (100 μg/mL) in the presence or absence of GW9508 (50 μM) or AH9614 (1 μM) for 24 h. The LDH assay was used to determine cell death. The dihydroethidium (DHE) staining assay was used to measure intracellular levels of reactive oxidative species (ROS), and a senescence β-galactosidase assay kit was used to determine endothelial senescence. Gene and protein expressions were measured using real-time polymerase chain reaction (PCR) and western blot analysis, respectively. Ox-LDL treatment decreased the expression of GPR120 by more than half in HAECs. Typically, 100 μg/mL of ox-LDL- induced 35.2% LDH release, which was reduced to 16.9% by 50 μM GW9508, the agonist of GPR120. Importantly, GW9508 relieved cytotoxicity and suppressed the ox-LDL-induced increase in the activity of senescence-associated β-galactosidase (SA-β-Gal) (from 3.3-fold to 1.6-fold of the control group) and the generation of cellular reactive oxidative species (ROS) (from 3.8-fold to 1.6-fold of the control group). Furthermore, we found that GW9508 ameliorated ox-LDL-induced endothelial cell cycle arrest at the G0/G1 phase and the expression of key senescence proteins, including p53 and plasminogen activator inhibitor-1(PAI-1). Mechanistically, we showed that GW9508 promoted ox-LDL-induced transcriptional factor NF-E2-related factor 2 (NRF2) (increase by 47.3%) translocation into the nucleus. The effect of GW9508 is dependent on its receptor GPR120, the blockage of which by its specific antagonist, AH7614, abolished the antisenescence effect of GW9508. Collectively, this study revealed the protective effect of GPR120 activation in vascular endothelial cells, implying that GPR120 is a promising therapeutic target for the treatment of cardiovascular diseases.
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http://dx.doi.org/10.1021/acsomega.0c03581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758881PMC
December 2020

Dietary oleic acid supplementation and blood inflammatory markers: a systematic review and meta-analysis of randomized controlled trials.

Crit Rev Food Sci Nutr 2020 Dec 11:1-18. Epub 2020 Dec 11.

Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, Wuxi, China.

The aim of this systematic review and meta-analysis was to analyze data from randomized controlled trials (RCTs) assessing the effects of oleic acid (OA) supplementation on blood inflammatory markers in adults. PubMed, EMBASE and Cochrane Library databases were systematically searched from 1950 to 2019, with adults and a minimum intervention duration of 4 weeks. The effect size was estimated, adopting standardized mean difference (SMD) and 95% confidence interval (CI). Of the 719 identified studies, thirty-one RCTs involving 1634 subjects were eligible. The results of this study revealed that increasing OA supplementation significantly reduced C-reactive protein (CRP) (SMD: -0.11, 95% CI: -0.21, -0.01, P = 0.038). However, dietary OA consumption did not significantly affect tumor necrosis factor (TNF) (SMD: -0.05, 95% CI: -0.19, 0.10, P = 0.534), interleukin 6 (IL-6) (SMD: 0.01, 95% CI: -0.10, 0.13, P = 0.849), fibrinogen (SMD: 0.08, 95% CI: -0.16, 0.31, P = 0.520), plasminogen activator inhibitor type 1 (PAI-1) activity (SMD: -0.11, 95% CI: -0.34, 0.12, P = 0.355), soluble intercellular adhesion molecule-1 (sICAM-1) (SMD: -0.06, 95% CI: -0.26, 0.13, P = 0.595) or soluble vascular cell adhesion molecule-1 (sVCAM-1) (SMD: -0.04, 95% CI: -0.27, 0.18, P = 0.701). Overall, the meta-analysis demonstrated that dietary OA supplementation significantly reduced CRP, yet did not affect other inflammatory markers including TNF, IL-6, fibrinogen, PAI-1 activity, sICAM-1or sVCAM-1.
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http://dx.doi.org/10.1080/10408398.2020.1854673DOI Listing
December 2020

Rapid Screening α-Glucosidase Inhibitors from Natural Products by At-Line Nanofractionation with Parallel Mass Spectrometry and Bioactivity Assessment.

J Chromatogr A 2021 Jan 23;1635:461740. Epub 2020 Nov 23.

Institute of Pharmaceutical Analysis, College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine & New Drug Research, Jinan University, Guangzhou 510632, China. Electronic address:

In this study, a novel at-line nanofractionation screening platform was successfully developed for the rapid screening and identification of α-glucosidase inhibitors from natural products. A time-course bioassay based on high density well-plates was performed in parallel with high resolution mass spectrometry (MS), providing a straightforward and rapid procedure to simultaneously obtain chemical and biological information of active compounds. Through multiple nanofractionations into the same well-plate and comparisons of the orthogonal separation results of hydrophilic interaction liquid chromatography (HILIC) and reversed-phase liquid chromatography (RPLC), the α-glucosidase inhibitors can be accurately identified from co-eluates. The screening platform was comprehensively evaluated and validated, and was applied to the screenings of green tea polyphenols and Ginkgo folium flavonoids. After accurate peak shape and retention time matching between the bioactivity chromatograms and MS chromatograms, ten α-glucosidase inhibitors were successfully screened out and identified. The proposed screening method is rapid, effective and can avoid ignoring low abundant/active inhibitors.
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http://dx.doi.org/10.1016/j.chroma.2020.461740DOI Listing
January 2021

Characterization and determination of free phytosterols and phytosterol conjugates: The potential phytochemicals to classify different rice bran oil and rice bran.

Food Chem 2021 May 12;344:128624. Epub 2020 Nov 12.

National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.

Phytosterols are important beneficial compounds found in rice bran (RB) and rice bran oil (RBO). Although relationships have been confirmed between the forms of phytosterols and their bioactivities, the analysis of different forms of phytosterols in RB and RBO has been lacking. In this study, high temperature gas chromatography-mass spectrometry (HTGC-MS) was combined with the single standard to determine multi-components (SSDMC) method to determine free sterols (FSs) and steryl glycosides (SGs) in RB and RBO. High-performance liquid chromatography (HPLC) was used to determine steryl ferulates (SFs). There was clear variation in the composition of FS, SF and SG, indicating that different forms of phytosterols can discriminate between different RB and RBO. The developed method may be also useful for the detection of other compounds of interest in oils, oil seeds or cereals.
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http://dx.doi.org/10.1016/j.foodchem.2020.128624DOI Listing
May 2021

Characterization of fatty acids, triacylglycerols, phytosterols and tocopherols in peony seed oil from five different major areas in China.

Food Res Int 2020 11 9;137:109416. Epub 2020 Jun 9.

Synergetic Innovation Center of Food Safety and Nutrition, State Key Laboratory of Food Science and Technology, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, People's Republic of China. Electronic address:

Peony (Paeonia lactiflora pall) is a unique plant in China, which is planted on a large scale in different areas. The study characterized the triacylglycerol (TAG), fatty acid (FA), phytosterol, and tocopherol in peony seed oil (PSO) from five cultivation areas in China. The FAs in PSO were mainly C fatty acyl chains, especially α-linolenic acid (C). The triacylglycerol of PSO was identified by UPLC-Q-ToF/MS, and the predominant TAGs were LnLnLn, LLnLn, LLLn, LnLO/LLL, and OOLn/OLL. As for the micronutrients, γ-tocopherol and β-sitosterol were main components of tocopherol and phytosterol, respectively. The obtained data were further analyzed by principal components analysis (PCA), which allowed differentiation of five PSOs by their cultivation areas. For the great potential in unsaturated fatty acid and micronutrients, PSO could be a good dietary resource of plant oil.
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http://dx.doi.org/10.1016/j.foodres.2020.109416DOI Listing
November 2020

Identification and in vitro anti-inflammatory activity of different forms of phenolic compounds in Camellia oleifera oil.

Food Chem 2021 May 18;344:128660. Epub 2020 Nov 18.

School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, China.

Camellia oleifera (C. oleifera) oil is known as "oriental olive oil". We previously reported the anti-inflammatory activity of C. oleifera oil was mainly attributed to the phenolic compounds, but the specific compounds remain uncovered. In this study, phenolic compounds in the form of free (11.92 μg GAE/g), esterified (37.57 μg GAE/g), glycosylated (128.71 μg GAE/g), and insoluble (47.53 μg GAE/g) were prepared from C. oleifera oil. Their anti-inflammatory activities were evaluated by lipopolysaccharide induced RAW 264.7 macrophage. Glycosylated fraction showed the highest anti-inflammatory activity as indicated by the low production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Subsequently, 13 different glycosylated polyphenols were identified by UPLC-Q-TOF/MS, and the major compounds were purified for anti-inflammatory re-evaluation. Lower anti-inflammatory activities of compound 3 and compound 6 were observed when compared to kaempferol. Overall, these results would promote the utilization of phenolic compounds in C. oleifera oil.
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http://dx.doi.org/10.1016/j.foodchem.2020.128660DOI Listing
May 2021

Antioxidant interaction of α-tocopherol, γ-oryzanol and phytosterol in rice bran oil.

Food Chem 2021 May 22;343:128431. Epub 2020 Oct 22.

National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu PR China.

In this study, purified rice bran oil (RBO) was used as a lipid matrix model to study the individual and binary antioxidant capacity of the minor constituents (α-tocopherol, γ-oryzanol and phytosterol) added at different concentrations and ratios. The results revealed that concentration influenced on the oxidation stability and scavenging capacity, while ratio mainly affected the type of interaction or the degree of synergism or antagonism. It was important to notice that the antioxidant capacity of α-tocopherol would decrease under high concentration. Besides, the inhibition of phytosterol on α-tocopherol and the formation of hydrogen bond between γ-oryzanol and phytosterol were speculated by the interactions of these minor constituents. This work helps to select efficient combinations for stabilizing the anti-oxidation of nutrient enriched RBO or provide suggestions for moderate retain of minor constituents in RBO.
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http://dx.doi.org/10.1016/j.foodchem.2020.128431DOI Listing
May 2021

lncRNA RP11-624L4.1 Is Associated with Unfavorable Prognosis and Promotes Proliferation via the CDK4/6-Cyclin D1-Rb-E2F1 Pathway in NPC.

Mol Ther Nucleic Acids 2020 Dec 15;22:1025-1039. Epub 2020 Oct 15.

NHC Key Laboratory of Cancer Proteomics, Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in southern China and southeast Asia. Emerging evidence revealed that long noncoding RNAs (lncRNAs) might play important roles in the development and progression of many cancers, including NPC. The functions and mechanisms of the vast majority of lncRNAs involved in NPC remain unknown. In this study, a novel lncRNA RP11-624L4.1 was identified in NPC tissues using next-generation sequencing. hybridization (ISH) was used to analyze the correlation between RP11-624L4.1 expression and the clinicopathological features or prognosis in NPC patients. RNA-Protein Interaction Prediction (RPISeq) predictions and RNA-binding protein immunoprecipitation (RIP) assays were used to identify RP11-624L4.1's interactions with cyclin-dependent kinase 4 (CDK4). As a result, we found that RP11-624L4.1 is hyper-expressed in NPC tissues, which was associated with unfavorable prognosis and clinicopathological features in NPC. By knocking down and overexpressing RP11-624L4.1, we also found that it promotes the proliferation ability of NPC and through the CDK4/6-Cyclin D1-Rb-E2F1 pathway. Overexpression of CDK4 in knocking down RP11-624L4.1 cells can partially rescue NPC promotion, indicating its role in the RP11-624L4.1-CDK4/6-Cyclin D1-Rb-E2F1 pathway. Taken together, RP11-624L4.1 is required for NPC unfavorable prognosis and proliferation through the CDK4/6-Cyclin D1-Rb-E2F1 pathway, which may be a novel therapeutic target and prognostic in patients with NPC.
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http://dx.doi.org/10.1016/j.omtn.2020.10.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558227PMC
December 2020

Connectivity Mapping Identifies BI-2536 as a Potential Drug to Treat Diabetic Kidney Disease.

Diabetes 2021 02 16;70(2):589-602. Epub 2020 Oct 16.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY

Diabetic kidney disease (DKD) remains the most common cause of kidney failure, and the treatment options are insufficient. Here, we used a connectivity mapping approach to first collect 15 gene expression signatures from 11 DKD-related published independent studies. Then, by querying the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 data set, we identified drugs and other bioactive small molecules that are predicted to reverse these gene signatures in the diabetic kidney. Among the top consensus candidates, we selected a PLK1 inhibitor (BI-2536) for further experimental validation. We found that PLK1 expression was increased in the glomeruli of both human and mouse diabetic kidneys and localized largely in mesangial cells. We also found that BI-2536 inhibited mesangial cell proliferation and extracellular matrix in vitro and ameliorated proteinuria and kidney injury in DKD mice. Further pathway analysis of the genes predicted to be reversed by the PLK1 inhibitor was of members of the TNF-α/NF-κB, JAK/STAT, and TGF-β/Smad3 pathways. In vitro, either BI-2536 treatment or knockdown of PLK1 dampened the NF-κB and Smad3 signal transduction and transcriptional activation. Together, these results suggest that the PLK1 inhibitor BI-2536 should be further investigated as a novel therapy for DKD.
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http://dx.doi.org/10.2337/db20-0580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881868PMC
February 2021

Determination of low-abundance single-base point mutations based on endonuclease IV and branch migration system.

Anal Chim Acta 2020 Oct 20;1134:28-33. Epub 2020 Aug 20.

Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China. Electronic address:

Combining endonuclease IV and branch migration competition systems, we have designed a new single-base mutation detection method which is capable of thermostatic, sensitive, simple, and cost-effective at the same time, while other probe method based on endonuclease IV hardly achieve. Our method has better discrimination factors (6.81-83.10) and a low abundance detection limit of mutant-type DNA (MT) (0.05% mutant-type DNA/total DNA) without complex temperature optimize process. The concentration detection limit of MT is 0.03 nM.The abundance detection limit for EGFR L858R (0.1%) and PTEN R130Q (0.05%) in clinical samples suggested that the method has potential applications in clinical diagnosis.
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http://dx.doi.org/10.1016/j.aca.2020.08.014DOI Listing
October 2020

Mice lacking DUSP6/8 have enhanced ERK1/2 activity and resistance to diet-induced obesity.

Biochem Biophys Res Commun 2020 11 8;533(1):17-22. Epub 2020 Sep 8.

Department of Biomedical Sciences, Grand Valley State University, Allendale, MI, 49401, USA.

Extracellular signal-regulated kinase 1 and 2 (ERK1/2) have been implicated as important regulators of metabolic homeostasis. Here we generated a new mouse model with genetic deletion of two ERK1/2 phosphatases, dual specificity phosphatase (DUSP) 6 and 8, to further define the role of ERK1/2 in obesity development. Dusp6/8 double-null mice demonstrated elevated ERK1/2 phosphorylation in multiple tissues, without any change of phosphorylation of p38 and c-Jun N-terminal kinases (JNKs). Elevated ERK1/2 activity in Dusp6/8 double-null mice was associated with larger hearts and other organs, consistent with greater rate of cell proliferation in these mice. However, ERK1/2 activation was not sufficient to protect the mouse hearts from pathological hypertrophy and interstitial fibrosis following angiotensin II and phenylephrine stimulation. Interestingly, mice lacking DUSP6/8 were resistant to high-fat diet-induced obesity. Serum triglyceride, lipid content in the liver and visceral adipose tissues was also dramatically reduced in Dusp6/8 double-null mice. Furthermore, Dusp6/8 double-null mice had improved glucose tolerance. Mechanistically, we found out that elevated ERK1/2 activity increased the expression levels of genes involved in lipid metabolism and glucose homeostasis. Together, our data suggest that ERK1/2 play an essential role for the management of metabolic homeostasis.
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http://dx.doi.org/10.1016/j.bbrc.2020.08.106DOI Listing
November 2020

Tubular HIPK2 is a key contributor to renal fibrosis.

JCI Insight 2020 09 3;5(17). Epub 2020 Sep 3.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

We previously used global Hipk2-null mice in various models of kidney disease to demonstrate the central role of homeodomain-interacting protein kinase 2 (HIPK2) in renal fibrosis development. However, renal tubular epithelial cell-specific (RTEC-specific) HIPK2 function in renal fibrogenesis has yet to be determined. Here, we show that modulation of tubular HIPK2 expression and activity affects renal fibrosis development in vivo. The loss of HIPK2 expression in RTECs resulted in a marked diminution of renal fibrosis in unilateral ureteral obstruction (UUO) mouse models and HIV-associated nephropathy (HIVAN) mouse models, which was associated with the reduction of Smad3 activation and downstream expression of profibrotic markers. Conversely, WT HIPK2 overexpression in RTECs accentuated the extent of renal fibrosis in the setting of UUO, HIVAN, and folic acid-induced nephropathy in mice. Notably, kinase-dead HIPK2 mutant overexpression or administration of BT173, an allosteric inhibitor of HIPK2-Smad3 interaction, markedly attenuated the renal fibrosis in these mouse models of kidney disease, indicating that HIPK2 requires both the kinase activity and its interaction with Smad3 to promote TGF-β-mediated renal fibrosis. Together, these results establish an important RTEC-specific role of HIPK2 in kidney fibrosis and further substantiate the inhibition of HIPK2 as a therapeutic approach against renal fibrosis.
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http://dx.doi.org/10.1172/jci.insight.136004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526443PMC
September 2020

Acetylation-mediated degradation of HSD17B4 regulates the progression of prostate cancer.

Aging (Albany NY) 2020 07 17;12(14):14699-14717. Epub 2020 Jul 17.

Department of Oncology, NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha 410008, China.

Steroidogenic enzymes are crucial in prostate cancer (PCa) progression. 17β-Hydroxysteroid dehydrogenase type 4 (HSD17B4), encoded by HSD17B4, lacks catalytic capacity in androgen metabolism. Now the detailed role and molecular mechanism of PCa development are largely unknown. Here we showed that the expression of HSD17B4 was increased in PCa tissues compared to paired paratumor tissues. HSD17B4 knockdown in PCa cells significantly suppressed its proliferation, migration and invasion, while overexpressing HSD17B4 had opposite effects. Mechanistically, we found that the protein level of HSD17B4 was regulated by its acetylation at lysine 669(K669). Dihydroxytestosterone (DHT) treatment increased HSD17B4 acetylation and then promoted its degradation via chaperone-mediated autophagy (CMA). SIRT3 directly interacted with HSD17B4 to inhibit its acetylation and enhance its stability. In addition, we identified CREBBP as a regulator of the K669 acetylation and degradation of HSD17B4, affecting PC cell proliferation, migration and invasion. Notably, in PCa tissues and paired paratumor tissues, the level of HSD17B4 was negatively correlated with its K669 acetylation. Taken together, this study identified a novel role of HSD17B4 in PCa progression and suggested that HSD17B4 and its upstream regulators may be potential therapeutic targets for PCa intervention.
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http://dx.doi.org/10.18632/aging.103530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425433PMC
July 2020

Role of SIRT1 in HIV-associated kidney disease.

Am J Physiol Renal Physiol 2020 08 13;319(2):F335-F344. Epub 2020 Jul 13.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.

Human immunodeficiency virus (HIV) infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We have previously shown that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3, were increased in HIVAN kidneys. Here, we demonstrate the key role of sirtuin 1 (SIRT1) deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in the glomeruli of human and mouse HIVAN kidneys and that HIV-1 gene expression was associated with reduced SIRT1 expression and increased acetylation of NF-κB p65 and STAT3 in cultured podocytes. Interestingly, SIRT1 overexpression, in turn, reduced the expression of negative regulatory factor in podocytes stably expressing HIV-1 proviral genes, which was associated with inactivation of NF-κB p65 and a reduction in HIV-1 long terminal repeat promoter activity. In vivo, the administration of the small-molecule SIRT1 agonist BF175 or inducible overexpression of SIRT1 specifically in podocytes markedly attenuated albuminuria, kidney lesions, and expression of inflammatory markers in Tg26 mice. Finally, we showed that the reduction in SIRT1 expression by HIV-1 is in part mediated through miR-34a expression. Together, our data provide a new mechanism of SIRT1 regulation and its downstream effects in HIV-1-infected kidney cells and indicate that SIRT1/miR-34a are potential drug targets to treat HIV-related kidney disease.
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http://dx.doi.org/10.1152/ajprenal.00140.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473906PMC
August 2020

SOX10 - A Novel Marker for the Differential Diagnosis of Breast Metaplastic Squamous Cell Carcinoma.

Cancer Manag Res 2020 28;12:4039-4044. Epub 2020 May 28.

Department of Pathology, School of Basic Medical Science, Central South University, Changsha 410013, People's Republic of China.

Introduction: Differential diagnosis of metaplastic squamous cell carcinoma of breast (MSCCB) is difficult. In particular, in terms of metastatic MSCCB, because of the low speciality of traditional markers such as mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15) and GATA binding protein 3 (GATA3), the most common problem is differentiating the spread of MSCCB to the lung from a primary lung squamous cell carcinoma. It is urgently required to explore a novel marker to aid in differential diagnosis.

Aim: The aim of this study is to explore a novel marker to aid in the differential diagnosis of MSCCB from other squamous cell carcinomas (SCC) in other organs.

Methods: We tested the expression of SOX10 in 375 human SCC specimens with immunohistochemistry (IHC).

Results: In a series of 20 MSCCB, 9 (45%) were positive for SOX10. All of them were triple-negative MSCCB. Conversely, SOX10 was totally negative in another 205 SCC originating from lung, skin, cervix, oral mucosa, and esophagus. In a series of 150 triple-negative breast cancer and their metastatic foci, SOX10 labeling in the primary tumor and metastasis was 78% and 79.3%, respectively, and the agreement rate was 97.3% (>0.05).

Conclusion: Our findings demonstrate that SOX10 was recommended for differentiating MSCCB from non-mammary metastasis to the breast, as well as for distinguishing primary SCC from metastatic MSCCB, and SOX10 may be valuable in the pathological diagnosis of breast-derived metaplastic squamous cell carcinoma.
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http://dx.doi.org/10.2147/CMAR.S250867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266319PMC
May 2020

Analysis of Phytochemical Composition of Camellia oleifera Oil and Evaluation of its Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages.

Lipids 2020 07 11;55(4):353-363. Epub 2020 May 11.

International Joint Research Laboratory for Lipid Nutrition and Safety, Synergetic Innovation Center of Food Safety and Nutrition, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province, 214122, PR China.

In China, Camellia oleifera oil (COO) is not only a common edible oil but also a traditional remedy widely applied to ameliorate a variety of illnesses associated with inflammation, such as mouth ulcers, thrush, eczema, etc. However, there has been a lack of relevant biological research on the anti-inflammatory capacity of COO, and the specific bioactive lipid phytochemicals contributing to the anti-inflammatory effect need further research. In this study, the RAW 264.7 macrophages model was used to investigate the anti-inflammatory capacity of COO. Our data showed that 33-200 μg/mL COO markedly inhibited the lipopolysaccharide lipopolysaccharide (LPS)-stimulated nitric oxide (NO.) secretion via the suppression of Nos2 and Cox-2 expression. The enzyme immunoassay confirmed that COO also exhibited a strong suppressive effect on the expression of proinflammatory cytokines such as Tnf-α and Il-6. To further explore the correlation between the anti-inflammatory effects and the lipid phytochemicals in COO, 10 samples were collected and screened for their chemical compositions. It was interestingly demonstrated that the polyphenol extracts of COO play a vital role in its anti-inflammatory properties. In addition, an oil-in-water (O/W) emulsion-based system was also developed to deliver the liposoluble COO into the cells, and the feasibility of this system was confirmed. Our research confirms the anti-inflammatory potential of COO and highlights that the main functional ingredient is polyphenol extracts. This may provide a scientific basis for the comprehensive utilization and development of COO and related functional foods.
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http://dx.doi.org/10.1002/lipd.12241DOI Listing
July 2020

Haplotype-resolved genomes provide insights into structural variation and gene content in Angus and Brahman cattle.

Nat Commun 2020 04 29;11(1):2071. Epub 2020 Apr 29.

The Davies Research Centre, School of Animal and Veterinary Sciences, University of Adelaide, Roseworthy, SA, 5371, Australia.

Inbred animals were historically chosen for genome analysis to circumvent assembly issues caused by haplotype variation but this resulted in a composite of the two genomes. Here we report a haplotype-aware scaffolding and polishing pipeline which was used to create haplotype-resolved, chromosome-level genome assemblies of Angus (taurine) and Brahman (indicine) cattle subspecies from contigs generated by the trio binning method. These assemblies reveal structural and copy number variants that differentiate the subspecies and that variant detection is sensitive to the specific reference genome chosen. Six genes with immune related functions have additional copies in the indicine compared with taurine lineage and an indicus-specific extra copy of fatty acid desaturase is under positive selection. The haplotyped genomes also enable transcripts to be phased to detect allele-specific expression. This work exemplifies the value of haplotype-resolved genomes to better explore evolutionary and functional variations.
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http://dx.doi.org/10.1038/s41467-020-15848-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190621PMC
April 2020

A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma.

Cell Death Dis 2020 02 3;11(2):89. Epub 2020 Feb 3.

Department of Oncology, NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha, 410008, People's Republic of China.

Abnormal expression of the E3 ubiquitin ligase A20 has been found in some malignant cancers, including hepatocellular carcinoma (HCC). Here, we discovered that A20 is an E3 ubiquitin ligase for phosphofructokinase, liver type (PFKL) in HCC A20 interacts with PFKL and promotes its degradation, therefore inhibiting glycolysis in HCC cell lines. Downregulation of A20 in HCC cells promotes proliferation, migration, and glycolysis, all of which can be inhibited by targeting PFKL with RNA interference. Importantly, A20 is downregulated in advanced HCC tissues and inversely correlated with PFKL expression. Thus, our findings establish A20 as a critical regulator of glycolysis and reveal a novel mechanism for A20 in tumor suppression and PFKL regulation. Given that an increased level of glycolysis is linked with HCC, this study also identifies potential therapeutic targets for HCC treatment.
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http://dx.doi.org/10.1038/s41419-020-2278-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997366PMC
February 2020

Analysis of left ventricular diastolic energy loss in patients with aortic stenosis with preserved ejection fraction by using vector flow mapping.

Echocardiography 2019 12;36(12):2216-2226

Department of Ultrasound, Henan Provincial People's Hospital Heart Center, Fuwai Central China Cardiovascular Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.

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http://dx.doi.org/10.1111/echo.14555DOI Listing
December 2019

New insights into mammalian sex chromosome structure and evolution using high-quality sequences from bovine X and Y chromosomes.

BMC Genomics 2019 Dec 19;20(1):1000. Epub 2019 Dec 19.

The Davies Research Centre, School of Animal and Veterinary Sciences, University of Adelaide, Roseworthy, South Australia, Australia.

Background: Mammalian X chromosomes are mainly euchromatic with a similar size and structure among species whereas Y chromosomes are smaller, have undergone substantial evolutionary changes and accumulated male specific genes and genes involved in sex determination. The pseudoautosomal region (PAR) is conserved on the X and Y and pair during meiosis. The structure, evolution and function of mammalian sex chromosomes, particularly the Y chromsome, is still poorly understood because few species have high quality sex chromosome assemblies.

Results: Here we report the first bovine sex chromosome assemblies that include the complete PAR spanning 6.84 Mb and three Y chromosome X-degenerate (X-d) regions. The PAR comprises 31 genes, including genes that are missing from the X chromosome in current cattle, sheep and goat reference genomes. Twenty-nine PAR genes are single-copy genes and two are multi-copy gene families, OBP, which has 3 copies and BDA20, which has 4 copies. The Y chromosome X-d1, 2a and 2b regions contain 11, 2 and 2 gametologs, respectively.

Conclusions: The ruminant PAR comprises 31 genes and is similar to the PAR of pig and dog but extends further than those of human and horse. Differences in the pseudoautosomal boundaries are consistent with evolutionary divergence times. A bovidae-specific expansion of members of the lipocalin gene family in the PAR reported here, may affect immune-modulation and anti-inflammatory responses in ruminants. Comparison of the X-d regions of Y chromosomes across species revealed that five of the X-Y gametologs, which are known to be global regulators of gene activity and candidate sexual dimorphism genes, are conserved.
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http://dx.doi.org/10.1186/s12864-019-6364-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923926PMC
December 2019

Health benefits of 4,4-dimethyl phytosterols: an exploration beyond 4-desmethyl phytosterols.

Food Funct 2020 Jan;11(1):93-110

National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu Province, China.

4,4-Dimethyl phytosterols possess two methyl groups at the carbon-4 atom of the aliphatic A-ring. The methyl groups are crucial for the molecular recognition of endogenous and exogenous bioactive compounds. Phytosterols have received worldwide attention owing to their recognized health benefits. However, 4,4-dimethyl phytosterols are less appreciated. Recent research studies revealed that 4,4-dimethyl phytosterols exert numerous beneficial effects on disease prevention, and are particularly involved in the endogenous cannabinoid system (ECS). The purpose of this review is to summarize and highlight the currently available information regarding the structures and sources of 4,4-dimethyl phytosterols, and to provide detailed preclinical studies performed to evaluate their potential for treating various diseases. Future research on 4,4-dimethyl phytosterols is warranted to confirm their relationship with the ECS, and to elucidate the mechanism directly toward clinical trials.
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http://dx.doi.org/10.1039/c9fo01205bDOI Listing
January 2020

Arctigenin attenuates diabetic kidney disease through the activation of PP2A in podocytes.

Nat Commun 2019 10 4;10(1):4523. Epub 2019 Oct 4.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Arctigenin (ATG) is a major component of Fructus Arctii, a traditional herbal remedy that reduced proteinuria in diabetic patients. However, whether ATG specifically provides renoprotection in DKD is not known. Here we report that ATG administration is sufficient to attenuate proteinuria and podocyte injury in mouse models of diabetes. Transcriptomic analysis of diabetic mouse glomeruli showed that cell adhesion and inflammation are two key pathways affected by ATG treatment, and mass spectrometry analysis identified protein phosphatase 2 A (PP2A) as one of the top ATG-interacting proteins in renal cells. Enhanced PP2A activity by ATG reduces p65 NF-κB-mediated inflammatory response and high glucose-induced migration in cultured podocytes via interaction with Drebrin-1. Importantly, podocyte-specific Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection. Collectively, our results demonstrate a renoprotective mechanism of ATG via PP2A activation and establish PP2A as a potential target for DKD progression.
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http://dx.doi.org/10.1038/s41467-019-12433-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778111PMC
October 2019