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1.
Mol Cell ; 81(16): 3262-3274.e3, 2021 08 19.
Article in English | MEDLINE | ID: mdl-34214466

ABSTRACT

N-degron pathways are a set of proteolytic systems that target the N-terminal destabilizing residues of substrates for proteasomal degradation. Recently, the Gly/N-degron pathway has been identified as a new branch of the N-degron pathway. The N-terminal glycine degron (Gly/N-degron) is recognized by ZYG11B and ZER1, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2). Here we present the crystal structures of ZYG11B and ZER1 bound to various Gly/N-degrons. The structures reveal that ZYG11B and ZER1 utilize their armadillo (ARM) repeats forming a deep and narrow cavity to engage mainly the first four residues of Gly/N-degrons. The α-amino group of the Gly/N-degron is accommodated in an acidic pocket by five conserved hydrogen bonds. These structures, together with biochemical studies, decipher the molecular basis for the specific recognition of the Gly/N-degron by ZYG11B and ZER1, providing key information for future structure-based chemical probe design.


Subject(s)
Cell Cycle Proteins/ultrastructure , Glycine/chemistry , Protein Conformation , Receptors, Cytokine/ultrastructure , Amino Acid Sequence/genetics , Cell Cycle Proteins/chemistry , Cell Cycle Proteins/genetics , Crystallography, X-Ray , Glycine/genetics , HEK293 Cells , Humans , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/ultrastructure , Protein Binding/genetics , Protein Domains/genetics , Proteolysis , Receptors, Cytokine/chemistry , Receptors, Cytokine/genetics , Substrate Specificity , Ubiquitin/genetics
2.
Int J Mol Sci ; 20(20)2019 Oct 13.
Article in English | MEDLINE | ID: mdl-31614951

ABSTRACT

Obesity is closely associated with neuroinflammation in the hypothalamus, which is characterized by over-activated microglia and excessive production of pro-inflammatory cytokines. The present study was aimed at elucidating the effects of (-)-epigallocatechin gallate (EGCG) on palmitic acid-stimulated BV-2 microglia and high-fat-diet-induced obese mice. The results indicated the suppressive effect of EGCG on lipid accumulation, pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) release, and microglial activation in both cellular and high-fat-diet rodent models. These results were associated with lower phosphorylated levels of the janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) signaling pathway. In conclusion, EGCG can attenuate high-fat-induced hypothalamic inflammation via inhibiting the JAK2/STAT3 signaling pathways in microglia.


Subject(s)
Anti-Obesity Agents/pharmacology , Catechin/analogs & derivatives , Microglia/drug effects , Obesity/drug therapy , Animals , Anti-Obesity Agents/therapeutic use , Catechin/pharmacology , Catechin/therapeutic use , Cell Line , Diet, High-Fat/adverse effects , Disease Models, Animal , Hypothalamus/drug effects , Hypothalamus/immunology , Hypothalamus/metabolism , Inflammation/metabolism , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Janus Kinase 2/metabolism , Lipid Metabolism/drug effects , Mice , Mice, Inbred C57BL , Mice, Obese , Microglia/metabolism , Obesity/metabolism , Palmitic Acid/metabolism , Palmitic Acid/pharmacology , Polyphenols/pharmacology , STAT3 Transcription Factor/metabolism , Tea/metabolism , Tumor Necrosis Factor-alpha/metabolism
3.
Clin Exp Pharmacol Physiol ; 45(1): 58-67, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28925507

ABSTRACT

Epigallocatechin-3-gallate (EGCG) is a type of catechin. It exhibits excellent antioxidant effects and anti-tumour activities for cancer chemoprevention. The mechanism of anti-tumour effects of EGCG on different cancers has been studied for the past few decades, but remains controversial. To investigate the potential role that EGCG may play in the epigenetic regulation of colorectal cancer (CRC) cell line, we integrated bioinformatics analysis with experimental validation. We found that levels of the enhancer of zeste homologue 2 (EZH2) were significantly higher in CRC tissues compared to normal adjacent tissues, based on the Genomic Data Commons (GDC) data portal. Different human CRC cell lines exhibited differing expression of levels of the EZH2 protein. In RKO cells, EGCG and the EZH2 inhibitor GSK343 exhibited similar inhibitory efficacy on the proliferation, invasion and migration abilities of the cells, and suppressed protein expression of trimethylated lysine 27 on histone H3 (H3K27me3), which may be caused by the loss of the enzymatic function of EZH2. EGCG and GSK343 were found to have a synergistic effect on the growth of RKO cells in lower concentrations. EZH2-correlated genes were enriched in the cell cycle pathway, the top-ranking up-regulated pathway in tumour tissues, based on pathway analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). In accord with this, we confirmed that EGCG and GSK343 could both significantly arrest the G0/G1 phase in RKO cell cycle, suggesting EGCG and EZH2 inhibitor share a common mechanism of action in RKO cells.


Subject(s)
Antineoplastic Agents/pharmacology , Catechin/analogs & derivatives , Colorectal Neoplasms/pathology , Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors , Indazoles/pharmacology , Pyridones/pharmacology , Apoptosis/drug effects , Catechin/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Humans , Neoplasm Invasiveness
4.
Clin Exp Pharmacol Physiol ; 44(12): 1180-1191, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28815679

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) and associated advanced liver diseases have become prevalent conditions in many countries and are associated with increased mortality. Gene expression profiles in NAFLD have been examined recently but changes in expression elicited by chemical compound treatments have not been investigated. Since (-)-Epigallocatechin-3-gallate (EGCG) and atorvastatin (ATST) exhibit similar efficacy in NAFLD models, we reasoned that some common key genes might alter after treatment of EGCG and ATST. Accordingly, we applied integrated bioinformatics analyses of RNA microarray data from EGCG and ATST treatment groups compared to controls in a NAFLD phenotypic mouse model. Using differential expression (DE) analysis, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA) and ClueGO enrichment, shared EGCG and ATST down-regulated pathways were identified which included extracellular matrix (ECM)-receptor interaction and protein processing in endoplasmic reticulum (ER). To refine key genes associated with liver fibrosis, a human NAFLD signature derived from patients of different fibrosis stages was analyzed. The results showed that fibrosis-related genes Col1a1, Col1a2, Col3a1 and Col6a3 were significantly down-regulated. These four genes were further validated as down-regulated in an independent mouse NAFLD dataset. We conclude that EGCG and ATST treatment results in the significant down-regulation of genes related to liver fibrosis.


Subject(s)
Atorvastatin/therapeutic use , Catechin/analogs & derivatives , Gene Expression/drug effects , Liver Cirrhosis/genetics , Non-alcoholic Fatty Liver Disease/genetics , Animals , Atorvastatin/administration & dosage , Catechin/administration & dosage , Catechin/therapeutic use , Disease Models, Animal , Down-Regulation , Fibrillar Collagens/genetics , Humans , Liver Cirrhosis/drug therapy , Male , Mice, Inbred C57BL , Multigene Family , Non-alcoholic Fatty Liver Disease/drug therapy
5.
Br J Pharmacol ; 181(13): 1897-1915, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38413375

ABSTRACT

BACKGROUND AND PURPOSE: Protein palmitoylation is involved in learning and memory, and in emotional disorders. Yet, the underlying mechanisms in these processes remain unclear. Herein, we describe that A-kinase anchoring protein 150 (AKAP150) is essential and sufficient for depressive-like behaviours in mice via a palmitoylation-dependent mechanism. EXPERIMENTAL APPROACH: Depressive-like behaviours in mice were induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Palmitoylated proteins in the basolateral amygdala (BLA) were assessed by an acyl-biotin exchange assay. Genetic and pharmacological approaches were used to investigate the role of the DHHC2-mediated AKAP150 palmitoylation signalling pathway in depressive-like behaviours. Electrophysiological recording, western blotting and co-immunoprecipitation were performed to define the mechanistic pathway. KEY RESULTS: Chronic stress successfully induced depressive-like behaviours in mice and enhanced AKAP150 palmitoylation in the BLA, and a palmitoylation inhibitor was enough to reverse these changes. Blocking the AKAP150-PKA interaction with the peptide Ht-31 abolished the CRS-induced AKAP150 palmitoylation signalling pathway. DHHC2 expression and palmitoylation levels were both increased after chronic stress. DHHC2 knockdown prevented CRS-induced depressive-like behaviours, as well as attenuating AKAP150 signalling and synaptic transmission in the BLA in CRS-treated mice. CONCLUSION AND IMPLICATIONS: These results delineate that DHHC2 modulates chronic stress-induced depressive-like behaviours and synaptic transmission in the BLA via the AKAP150 palmitoylation signalling pathway, and this pathway may be considered as a promising novel therapeutic target for major depressive disorder.


Subject(s)
A Kinase Anchor Proteins , Basolateral Nuclear Complex , Depression , Lipoylation , Mice, Inbred C57BL , Animals , A Kinase Anchor Proteins/metabolism , Male , Mice , Depression/metabolism , Depression/psychology , Basolateral Nuclear Complex/metabolism , Stress, Psychological/metabolism , Behavior, Animal
6.
Food Sci Nutr ; 11(12): 7841-7854, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38107141

ABSTRACT

Jasmine tea is loved by most people who drink flower tea owing to its unique aroma, and it is known as the top of flower teas. In our study, the quantitative evaluation of the quality of jasmine tea and detection of aroma components were carried out. First, the flavor quality of 92 kinds of jasmine tea was evaluated using multiple sub-factor quality evaluation methods. According to the evaluation results, jasmine tea was divided into three types: "fresh and lovely" (FL), "heavy and thick" (HT), and "fresh and heavy" (FH). Gas chromatography-mass spectrometry (GC-MS) was used to detect the aroma components of the three types of jasmine tea samples. α-Farnesene, cis-3-hexenyl benzoate, acid phenylmethyl ester, linalool, methyl anthranilate, and indole were the main substances that constituted the basic aroma quality characteristics of jasmine tea. Compared to the FL type, the HT and FH types were weaker in the diversification of the characteristic aroma and accumulation of green, herb, sweet, and roast aroma substances. Green and herb aromas play crucial roles in the fresh and persistent qualities of the three types of jasmine tea, which are the key quality factors research focus of jasmine tea.

7.
Front Microbiol ; 14: 1124546, 2023.
Article in English | MEDLINE | ID: mdl-36846747

ABSTRACT

Instant dark teas (IDTs) were individually liquid-state fermented using the fungi Aspergillus cristatus, Aspergillus niger, and Aspergillus tubingensis. To understand how the chemical constituents of IDTs were affected by the fungi, samples were collected and measured by liquid chromatography-tandem mass-tandem mass spectrometry (LC-MS/MS). Untargeted metabolomics analysis revealed that 1,380 chemical constituents were identified in positive and negative ion modes, and 858 kinds of chemical components were differential metabolites. Through cluster analysis, IDTs were different from the blank control, and their chemical constituents mostly included carboxylic acids and their derivatives, flavonoids, organooxygen compounds, and fatty acyls. And the metabolites of IDTs fermented by A. niger and A. tubingensis had a high degree of similarity and were classified into one category, which showed that the fungus used to ferment is critical to the formation of certain qualities of IDTs. The biosynthesis of flavonoids and phenylpropanoid, which involved nine different metabolites such as p-coumarate, p-coumaroyl-CoA, caffeate, ferulate, naringenin, kaempferol, leucocyanidin, cyanidin, and (-)-epicatechin, were significant pathways influencing the quality formation of IDTs. Quantification analysis indicated that the A. tubingensis fermented-IDT had the highest content of theaflavin, theabrownin, and caffeine, while the A. cristatus fermented-IDT had the lowest content of theabrownin, and caffeine. Overall, the results provided new insights into the relationship between the quality formation of IDTs and the microorganisms used in liquid-state fermentation.

8.
iScience ; 26(9): 107561, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37664599

ABSTRACT

Palmitoyl acyltransferases (PATs) have been suggested to be involved in learning and memory. However, the underlying mechanisms have not yet been fully elucidated. Here, we found that the activity of DHHC2 was upregulated in the hippocampus after fear conditioning, and DHHC2 knockdown impaired fear induced memory and long-term potentiation (LTP). Additionally, the activity of DHHC2 and its synaptic expression were increased after high frequency stimulation (HFS) or glycine treatment. Importantly, fear learning selectively augmented the palmitoylation level of AKAP150, not PSD-95, and this effect was abolished by DHHC2 knockdown. Furthermore, 2-bromopalmitic acid (2-BP), a palmitoylation inhibitor, attenuated the increased palmitoylation level of AKAP150 and the interaction between AKAP150 and PSD-95 induced by HFS. Lastly, DHHC2 knockdown reduced the phosphorylation level of GluA1 at Ser845, and also induced an impairment of LTP in the hippocampus. Our results suggest that DHHC2 plays a critical role in regulating fear memory via AKAP150 signaling.

9.
Int J Biol Macromol ; 214: 402-413, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35738342

ABSTRACT

Different cultivars and processing technologies involved in producing tea result in the high heterogeneity of derived polysaccharide conjugates, which limits the understanding of their composition and structure, and biological activity. Here, raw tea leaves from the same cultivar were used to produce dried fresh tea leaves, green tea, and black tea, and three polysaccharide conjugates derived from dried fresh tea leaves (FTPS), green tea (GTPS), and black tea (BTPS) were prepared accordingly. Their physiochemical characteristics and bioactivities were investigated. The results showed that the oxidation during tea processing increased the phenolics and proteins while decreasing the GalA in the derived TPS conjugates; meanwhile, it reduced the molecular weight and particle size of BTPS but enhanced their antioxidant activity in vitro. Furthermore, all three TPS conjugates improved intestinal homeostasis by reducing TJ protein loss and inflammation and alleviated DSS-induced colitis symptoms in mice. In addition, the three TPS conjugates showed differential regulation of the intestinal microbiome and altered the produced SCFAs, which contributed to the prevention of colitis. Our findings suggest that TPS conjugates could be applied in colitis prevention in association with the regulation of gut microbiota, and their efficacy could be optimized by employing suitable tea processing technologies.


Subject(s)
Camellia sinensis , Colitis , Animals , Camellia sinensis/chemistry , Colitis/chemically induced , Colitis/complications , Colitis/drug therapy , Dextran Sulfate/adverse effects , Homeostasis , Mice , Mice, Inbred C57BL , Polysaccharides/adverse effects , Tea/chemistry
10.
Nat Commun ; 13(1): 7636, 2022 Dec 10.
Article in English | MEDLINE | ID: mdl-36496439

ABSTRACT

N-degron pathway plays an important role in the protein quality control and maintenance of cellular protein homeostasis. ZER1 and ZYG11B, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2), recognize N-terminal (Nt) glycine degrons and participate in the Nt-myristoylation quality control through the Gly/N-degron pathway. Here we show that ZER1 and ZYG11B can also recognize small Nt-residues other than glycine. Specifically, ZER1 binds better to Nt-Ser, -Ala, -Thr and -Cys than to -Gly, while ZYG11B prefers Nt-Gly but also has the capacity to recognize Nt-Ser, -Ala and -Cys in vitro. We found that Nt-Ser, -Ala and -Cys undergo Nt-acetylation catalyzed by Nt-acetyltransferase (NAT), thereby shielding them from recognition by ZER1/ZYG11B in cells. Instead, ZER1/ZYG11B readily targets a selection of small Nt-residues lacking Nt-acetylation for degradation in NAT-deficient cells, implicating its role in the Nt-acetylation quality control. Furthermore, we present the crystal structures of ZER1 and ZYG11B bound to various small Nt-residues and uncover the molecular mechanism of non-acetylated substrate recognition by ZER1 and ZYG11B.


Subject(s)
Protein Processing, Post-Translational , Ubiquitin-Protein Ligases , Ubiquitin-Protein Ligases/metabolism , Acetylation , Myristic Acid , Glycine/metabolism
11.
Food Funct ; 12(24): 12291-12302, 2021 Dec 13.
Article in English | MEDLINE | ID: mdl-34816850

ABSTRACT

Understanding nonvolatile metabolite alterations during processing and their impacts on potential function is crucial for technological innovations in tea manufacturing. In the present work, specific metabolite alterations during Zijuan black tea processing and their potential effects on nicotine-induced human oral epithelial cell (HOEC) injury were investigated. The results showed that leucine, isoleucine, and tyrosine were the main hydrolysis products during withering, and theaflavin-3-gallate (TF-3-G), theaflavin-3'-gallate (TF-3'-G) and theaflavin-3,3'-gallate (TFDG) were mainly formed during rolling. Moreover, oxidation of flavonoid glycosides, catechins and dimeric catechins took place during fermentation. During drying, amino acid conversion became dominant. Meanwhile, processing samples effectively attenuated nicotine-induced oxidative stress and inflammation in HOECs. TF-3'-G, TF-3-G, phenylalanine, and kaempferol-3-coumaroylglucoside exhibited strong associations with protective action, which indicates that modifying the processes in which black tea are produced to be rich in those specific components could be beneficial for the oral health of people who smoke.


Subject(s)
Antioxidants/pharmacology , Epithelial Cells/drug effects , Oxidative Stress/drug effects , Tea/chemistry , Food Handling , Functional Food , Humans , Nicotine , Smoking/adverse effects
12.
J Zhejiang Univ Sci B ; 22(7): 548-562, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-34269008

ABSTRACT

Metformin, a first-line drug for type 2 diabetes mellitus, has been recognized as a potential anti-tumor agent in recent years. Epigallocatechin-3-gallate (EGCG), as the dominant catechin in green tea, is another promising adjuvant agent for tumor prevention. In the present work, the potential effect of EGCG on the anti-tumor efficacy of metformin in a mouse melanoma cell line (B16F10) was investigated. Results indicated that EGCG and metformin exhibited a synergistic effect on cell viability, migration, and proliferation, as well as signal transducer and activator of transcription 3/nuclear factor-κB (STAT3/NF-κB) pathway signaling and the production of inflammation cytokines. Meanwhile, the combination showed an antagonistic effect on cell apoptosis and oxidative stress levels. The combination of EGCG and metformin also differentially affected the nucleus (synergism) and cytoplasm (antagonism) of B16F10 cells. Our findings provide new insight into the potential effects of EGCG on the anti-tumor efficacy of metformin in melanoma cells.


Subject(s)
Antineoplastic Agents/pharmacology , Catechin/analogs & derivatives , Melanoma/drug therapy , Metformin/administration & dosage , Skin Neoplasms/drug therapy , Animals , Apoptosis , Catechin/administration & dosage , Cell Line, Tumor , Cell Movement , Cell Nucleus/metabolism , Cell Proliferation , Cell Survival , Cytokines/metabolism , Cytoplasm/metabolism , Inflammation , Melanoma, Experimental , Mice , NF-kappa B p50 Subunit/metabolism , Oxidative Stress , Phosphorylation , STAT3 Transcription Factor/metabolism , Spectrum Analysis, Raman
13.
J Agric Food Chem ; 69(50): 15362-15373, 2021 Dec 22.
Article in English | MEDLINE | ID: mdl-34904826

ABSTRACT

Black tea, as the most consumed kind of tea, is shown to have beneficial effects on human health. However, its impact on particulate matter (PM) induced lung injury and the mechanisms involved have been sparsely addressed. Here, we show that PM-exposed mice exhibited oxidative stress and inflammation in the lungs, which was significantly alleviated by a daily intake of black tea infusion (TI) in a concentration-dependent manner. Interestingly, both the ethanol-soluble fraction (ES) and the ethanol precipitate fraction (EP) exhibited better effects than those of TI; moreover, EP tended to have stronger protection than ES in some indicators, implying that EP played a dominant role in the prevention effects. Furthermore, fecal microbiota transplantation (FMT) revealed that the gut microbiota was differentially reshaped by TI and its fractions were able to directly alleviate the injury induced by PMs. These results indicate that daily intake of black tea and its fractions, especially EP, may alleviate particulate matter-induced lung injury via the gut-lung axis in mice. In addition, the Lachnospiraceae_NK4A136_group could be the core gut microbe contributing to the protection of EP and thus should be further studied in the future.


Subject(s)
Camellia sinensis , Lung Injury , Animals , Lung , Lung Injury/etiology , Lung Injury/prevention & control , Mice , Mice, Inbred C57BL , Particulate Matter/toxicity , Tea
14.
J Nanosci Nanotechnol ; 21(1): 623-631, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33213662

ABSTRACT

Natural siderite was selected as a raw material for preparing nano zero-valent iron (nZVI). The efficiency of the as-synthesized nZVI for PO3-4-P removal was investigated, and the effects of the annealing temperature, pH, initial PO3-4-P concentration, adsorption temperature and oxygen were investigated. The results indicated that after annealing at 550 °C, nZVI exhibited an average crystal size of 56.3 nm and a surface area of 14.1 m²/g. A decrease in pH and an increase in oxygen availability enhanced the removal efficiency. The adsorption process, which was spontaneous and exothermic according to the thermodynamic analysis, agreed well with the pseudo-second-order kinetic model. Based on the Langmuir equilibrium isotherms, the capacity of nZVI to adsorb phosphorus was determined to be 33.18 mg/L. The optimized conditions for the experimental conditions were defined by an orthogonal experiment as follows: initial P concentration 2 mg/L, initial pH 4, iron dose 2 g/L, adsorption time 60 min. The experimental results suggested that the as-prepared nZVI was a promising adsorbent for the removal of phosphate.

15.
Am J Transl Res ; 13(6): 6945-6951, 2021.
Article in English | MEDLINE | ID: mdl-34306447

ABSTRACT

OBJECTIVES: This study analyzed the effect of multi-platform extended care on postoperative self-efficacy and quality of life in patients with osteoporotic vertebral compressive fracture (OVCF). METHODS: 162 OVCF patients who underwent percutaneous vertebroplasty (PVP) or percutanous kyphoplasty (PKP) surgery in our hospital from January 2018 to June 2019 were classified into a control group (n=78) and an observation group (n=84) based on the admission time. The control group was given conventional health guidance and follow-up by telephone, and the observation group got multi-platform extended care. The postoperative incidence of re-fracture, Oswestry dysfunction index (ODI) before and after intervention, self-efficacy and quality of life were compared between the two groups. RESULTS: Incidence of re-fracture in the observation group was higher than that of the control group (P<0.05). The ODI scores of the two groups 3, 6, and 12 months after operation were lower than those on discharge (P<0.05), and the observation group had lower OD scores than the control group 6 and 12 months after operation (P<0.05). The self-efficacy scores of the two groups 6 months after discharge were higher than that on discharge (P<0.05), and the index in the observation group was higher than that of the control group (P<0.05). In addition, the scores of all dimensions of quality of life in two groups 6 months of discharge were higher than those on discharge (P<0.05), and the scores in the observation group were higher than those of the control group (P<0.05). CONCLUSION: Multi-platform extended care can effectively reduce the risk of postoperative re-fracture in OVCF patients, facilitate the improvement of patients' lumbar function, self-efficacy, and quality of life, and improve the prognosis of patients, which is worthy of clinical promotion.

16.
Front Pharmacol ; 12: 719842, 2021.
Article in English | MEDLINE | ID: mdl-34381369

ABSTRACT

Psoriasis, the most common skin inflammatory disease, is characterized by massive keratinocyte proliferation and immune cell infiltration into epidermis. L-Theanine (L-THE), a nonproteinogenic amino acid derived from green tea (Camellia sinensis), has been proved to possess the properties of anti-inflammatory, antidepressants and neuroprotective. However, whether L-THE has a therapeutic effect on psoriasis is still unknown. In this study, we found that the epidermal thickness and inflammatory response were significantly reduced in Imiquimod (IMQ)-induced psoriasis mice by applying with L-THE on mice skin. The expression of proliferation and inflammation associated genes such as keratin 17, IL-23 and CXCL1-3 was also downregulated by L-THE. Furthermore, L-THE inhibited the production of IL-23 in dendritic cells (DCs) after IMQ treatment, and decreased the levels of chemokines in keratinocytes treated with IL-17A by downregulating the expression of IL-17RA. RNA-seq and KEGG analysis revealed that L-THE significantly regulated the expression of IL-17A and NF-κB signaling pathway-associated genes. Metabolomics analysis displayed that L-THE promoted propanoate metabolism which has been reported to inhibit the activity of TH17 cells. Therefore, our results demonstrated that L-THE significantly decreases the levels of IL-23 and chemokines, and attenuates IMQ-induced psoriasis like skin inflammation by inhibiting the activation of NF-κB and IL-17A signaling pathways, and promoting the propanoate metabolism. Our findings suggest that topical applied L-THE can be used as a topical drug candidate for the treatment of psoriasis or as an adjuvant treatment of ustekinumab or secukinumab to prevent the relapse of psoriasis.

17.
Am J Transl Res ; 13(7): 8235-8240, 2021.
Article in English | MEDLINE | ID: mdl-34377311

ABSTRACT

PURPOSE: To assess the influence of pain care and hospice care on the quality of life of patients with advanced gastric cancer. METHODS: 136 patients with advanced gastric cancer were randomly divided into a experimental group (n=68) and a control group (n=68). The experimental group received pain care combined with hospice care, and control group received routine nursing. We measured quality of life and pain relief to assess the effect of pain care and hospice care. RESULTS: After nursing, the visual analogue scale (VAS) of the two groups decreased, the VAS score of the experimental group was lower than that of the control group (P < 0.05). Compared with the control group, the scores of SF-36 questionnaire (physiological function, psychological function, physical pain, emotional function, social function, and mental health) of the control group were lower than those of the experimental group (P < 0.05). CONCLUSIONS: Pain care and hospice care can effectively reduce the pain degree of patients with advanced gastric cancer and improve the quality of nursing.

18.
Nutrients ; 12(4)2020 Apr 10.
Article in English | MEDLINE | ID: mdl-32290071

ABSTRACT

Several studies in the past decades have reported anti-tumor activity of the bioactive compounds extracted from tea leaves, with a focus on the compound epigallocatechin-3-gallate (EGCG). However, further investigations are required to unravel the underlying mechanisms behind the anti-tumor activity of EGCG. In this study, we demonstrate that EGCG significantly inhibits the growth of 4T1 breast cancer cells in vitro and in vivo. EGCG ameliorated immunosuppression by significantly decreasing the accumulation of myeloid-derived suppressor cells (MDSCs) and increasing the proportions of CD4+ and CD8+ T cells in spleen and tumor sites in 4T1 breast tumor-bearing mice. Surprisingly, a low dose of EGCG (0.5-5 µg/mL) effectively reduced the cell viability and increased the apoptosis rate of MDSCs in vitro. EGCG down-regulated the canonical pathways in MDSCs, mainly through the Arg-1/iNOS/Nox2/NF-κB/STAT3 signaling pathway. Moreover, transcriptomic analysis suggested that EGCG also affected the non-canonical pathways in MDSCs, such as ECM-receptor interaction and focal adhesion. qRT-PCR further validated that EGCG restored nine key genes in MDSCs, including Cxcl3, Vcan, Col4a1, Col8a1, Oasl2, Mmp12, Met, Itsnl and Acot1. Our results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine breast tumor model.


Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/immunology , Catechin/analogs & derivatives , Myeloid-Derived Suppressor Cells/immunology , Phytotherapy , Polyphenols/pharmacology , Signal Transduction/drug effects , Signal Transduction/genetics , Tea/chemistry , Animals , Arginase/metabolism , Breast Neoplasms/genetics , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Catechin/isolation & purification , Catechin/pharmacology , Catechin/therapeutic use , Cell Line, Tumor , Disease Models, Animal , Female , Mice , Myeloid-Derived Suppressor Cells/metabolism , Myeloid-Derived Suppressor Cells/pathology , NADPH Oxidase 2/metabolism , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Polyphenols/isolation & purification , Polyphenols/therapeutic use , STAT3 Transcription Factor/metabolism
19.
Biochim Biophys Acta Mol Basis Dis ; 1866(10): 165856, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32512188

ABSTRACT

Epigallocatechin gallate (EGCG), as one of the main ingredients of green tea, has been reported to have potential prevention on a variety of solid tumors. However, the system-wide molecular mechanisms targeted to EGCG's anti-tumor effect have not been illustrated. Here, AGS and SGC7901 GC cells were used to investigate the EGCG-mediated change of gene expression. Our data showed that EGCG retarded cell growth and promoted cell death of GC in dose-dependent manner. Analyses based on transcription, translation as well as function were performed to explore the elusive anticancer role of EGCG. Of them, cell cycle was probably implicated key pathway of EGCG. Besides, our data revealed numerous LncRNAs activated after EGCG treatment. In this study, LINC00511 was discovered to be suppressed by EGCG and highly expressed in GC cells and tissues. Knockdown of LINC00511 inhibited cell growth and promoted cell death ratio in GC. Additionally, our data suggested LINC00511 could decrease the expression of miR-29b, followed by inducing GC development. Knockdown of miR-29b recovered the effects of LINC00511 silencing. In addition, we found overexpression of KDM2A, a target of miR-29b, would rescue the level of LINC00511. All the data showed that the LINC00511/miR-29b/KDM2A axis can be used as a diagnostic and therapeutic target for GC.


Subject(s)
Catechin/analogs & derivatives , Gene Expression Regulation, Neoplastic/drug effects , Stomach Neoplasms/drug therapy , Apoptosis/drug effects , Carcinogenesis/drug effects , Carcinogenesis/genetics , Catechin/pharmacology , Catechin/therapeutic use , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/genetics , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , F-Box Proteins/genetics , Gene Knockdown Techniques , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA-Seq , Stomach Neoplasms/pathology
20.
Quant Imaging Med Surg ; 9(4): 722-729, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31143663

ABSTRACT

BACKGROUND: Primitive neuroectodermal tumor (PNET) is extremely rare and highly aggressive with poor prognosis. Few studies concerning PNET's the imaging features have been published. METHODS: Six cases of PNET, all confirmed by pathology and immunohistochemical (IHC) examinations, were treated during January 2012 to December 2016. These cases' clinical course and imaging findings were retrospectively analyzed. RESULTS: Among six PNET cases, one located in left superior abdomen, one case at posterior abdominal wall, one case in right orbit, one case in left frontal temporal lobe, one case in pelvic cavity, and one case located in left supraclavicular fossa. The tumor's density was uniform for small tumor and heterogeneous for large tumors on CT images, while the size of tumors differed during presentation depending on the location of the tumor. Marked enhancement was visualized after injection of contrast media. The demarcation between the lesion and adjacent tissues or organs tended to be unclear. On magnetic resonance imaging (MRI) images, the mass mainly showed heterogeneously long T1 and long T2 signal intensity, mixed high signal intensity on fluid-attenuated inversion recovery (FLAIR) image. In two cases maximum intensity projection image reconstruction demonstrates tortuous blood vessels within the tumor on enhanced CT images. Five cases were treated by surgical resection with two cases received adjuvant radiotherapy and three cases received adjuvant chemotherapy. Six patients were followed up with a mean period of 34.5 months (ranging from 6 to 55 months). Five patients survived and one died. Among the five patients undergoing surgeries, one patient presented pelvic and abdominal recurrence/metastasis 2 months after abdominal PNET resection. One patient had a recurrent lesion in the right orbit involving the right ethmoid sinus 6 months after right orbital PNET resection. One patient's pelvic tumor recurred 7 months after PNET operation, and this patient died after 1 year and 10 months of follow-up. During the follow-up period, the remaining three cases did not show obvious recurrence and/or metastasis. CONCLUSIONS: Overall, the imaging appearances of PNET lack characteristics. PNETs generally do not have clear boundary, or partially so, with its adjacent organs or tissues suggesting their invasive nature. Upon further validation, maximum intensity projection image reconstruction demonstrates tortuous blood vessels within the tumor on enhanced CT images may be valuable information for the diagnosis of PNET.

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