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Darwish AB, Salama A, Essam Ibrahim Al-Samadi I. Formulation, optimisation, and evaluation of Lornoxicam-loaded Novasomes for targeted ulcerative colitis therapy: in vitro and in vivo investigations. J Drug Target 2025; 33:975-988. [PMID: 39831638 DOI: 10.1080/1061186x.2025.2456929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 12/31/2024] [Accepted: 01/15/2025] [Indexed: 01/22/2025]
Abstract
The purpose of this work was to create and assess Lornoxicam (LOR) loaded Novasomes (Novas) for the efficient treatment of ulcerative colitis. The study was performed using a 23 factorial design to investigate the impact of several formulation variables. Three separate parameters were investigated: Surface Active agent (SAA) type (X1), LOR concentration (X2), and SAA: Oleic acid ratio (X3). The dependent responses included encapsulation efficiency (Y1: EE %), particle size (Y2: PS), zeta potential (Y3: ZP), and polydispersity index (Y4: PDI). The vesicles demonstrated remarkable LOR encapsulation efficiency, ranging from 81.32 ± 3.24 to 98.64 ± 0.99%. The vesicle sizes ranged from 329 ± 9.88 to 583.4 ± 9.04 nm with high negative zeta potential values. The release pattern for Novas' LOR was biphasic and adhered to Higuchi's model. An in-vivo study assessed how LOR-Novas affected rats' acetic acid-induced ulcerative colitis (UC). The optimised LOR-Novas effectively reduced colonic ulceration (p < 0.05) and reduced the inflammatory pathway via inhibiting Toll-like receptor 4 (TLR4), Nuclear factor kappa β (NF-κβ) and inducible nitric oxide (iNO). At the same time, it elevated Silent information regulator-1(SIRT-1) and reduced glutathione (GSH) colon contents. Thus, the current study suggested that the formulation of LOR-Novas may be a viable treatment for ulcerative colitis.
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Affiliation(s)
| | - Abeer Salama
- Pharmacology Department, National Research Centre, Cairo, Egypt
| | - Inas Essam Ibrahim Al-Samadi
- Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt
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Liu GH, Wu F, Huo XY, Sun HB, Jin ZL, Gu YC, Guo DL, Zhou Y. Polycyclic Polyprenylated Acylphloroglucinols from Hypericum himalaicum. PLANTA MEDICA 2025. [PMID: 40294603 DOI: 10.1055/a-2596-3029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
Six previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) with a vicinal diol moiety (1: -6: ) were isolated from the whole plant of Hypericum himalaicum. Their structures were established through a comprehensive analysis of HRMS and 1D and 2D NMR data, while the absolute configurations were determined using the Mo2(OAc)4-induced circular dichroism (ICD), ECD, and NMR calculations. Compound 1: attenuated the secretion of NO, TNF-α, and IL-6, downregulated the protein expression of COX-2 and iNOS, and inhibited the release of ROS in LPS-induced RAW264.7 macrophages. Further investigation revealed that the anti-inflammatory effects may be attributed to the inhibition of the NF-κB and NLRP3 signaling pathways.
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Affiliation(s)
- Guang-Hui Liu
- Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, P. R. China
- University of Chinese Academy of Sciences, Beijing, P. R. China
| | - Fan Wu
- Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, P. R. China
- University of Chinese Academy of Sciences, Beijing, P. R. China
- Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, P. R. China
| | - Xue-Yan Huo
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, P. R. China
| | - Hong-Bing Sun
- Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, P. R. China
- University of Chinese Academy of Sciences, Beijing, P. R. China
- Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, P. R. China
| | - Zhuo-Lin Jin
- Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, P. R. China
- University of Chinese Academy of Sciences, Beijing, P. R. China
| | - Yu-Cheng Gu
- Syngenta Jealott's Hill International Research Centre, Bracknell, United Kingdom
| | - Da-Le Guo
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, P. R. China
| | - Yan Zhou
- Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, P. R. China
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Bates CA, Haber LT, Schoeny R, Maier A. Identification of mutagenicity, MOA, and dose response analysis. Food Chem Toxicol 2025; 202:115441. [PMID: 40222646 DOI: 10.1016/j.fct.2025.115441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 03/14/2025] [Accepted: 04/08/2025] [Indexed: 04/15/2025]
Abstract
Bates et al. (2023) developed a cancer risk assessment framework to evaluate dietary carcinogens. The framework 1) evaluates gene mutation as an early key event of cancer development; 2) considers the dose metric appropriate based on mode of action understanding; and 3) integrates the appropriate dose metric category with relevant exposure data to evaluate dose response options and cancer level of concern for the specified exposure scenario. Here, we test the framework with three demonstrated rodent carcinogens with varying human cancer assessments and underlying cancer biology: acrylamide, aflatoxin B1, and β-myrcene. While traditional cancer assessment approaches might characterize these chemicals as potential human carcinogens based primarily on rodent tumorigenicity data, the framework evaluates the cancer MOA in the context of exposure patterns to provide more information on conditions that may increase risk. We found that mutation is an early key event for aflatoxin B1 carcinogenicity, and linear low-dose extrapolation is an appropriate approach. In contrast, MOA data support a dose threshold-based approach for acrylamide and β-myrcene, and their respective dietary consumption patterns suggest a low concern for cancer. The framework provides a more nuanced approach to cancer risk assessment and provides for a more informed risk management decision.
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Affiliation(s)
| | - Lynne T Haber
- Risk Science Center, University of Cincinnati College of Medicine, United States
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Ding J, Zhu MZ, Liu SM, Liu RC, Xu S, Shehzadi K, Ma HL, Yu MJ, Zhu XH, Liang JH. Discovery of Orally Active Phenylquinoline-Based Soluble Epoxide Hydrolase Inhibitors with Anti-Inflammatory and Analgesic Activity. J Med Chem 2024; 67:18412-18447. [PMID: 39361006 DOI: 10.1021/acs.jmedchem.4c01766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
Currently, there are no specific drugs for treating acute pancreatitis. Soluble epoxide hydrolase (sEH) inhibitors show promise, but face challenges like low blood drug concentrations and potential adverse effects on CYP enzymes and the human ether-a-go-go-related gene (hERG). In this study, an approach involving scaffold hopping and structure-activity guided optimization was employed to design a series of phenylquinoline-based sEH inhibitors. Among these compounds, DJ-53 exhibited potent in vitro and in vivo effects in alleviating pain and reducing inflammation. The in vivo mechanism of action involved inhibiting sEH enzyme activity, thereby increasing levels of anti-inflammatory epoxyeicosatrienoic acids (EETs) and decreasing levels of proinflammatory dihydroxyeicosatrienoic acids (DHETs). Importantly, DJ-53 showed exceptional oral bioavailability and pharmacokinetics, while avoiding inhibition of CYP enzymes or the hERG channel. These results highlight DJ-53's potential as a new lead compound for anti-inflammatory and analgesic applications and provide a safe and effective scaffold for developing sEH inhibitors.
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Affiliation(s)
- Jing Ding
- Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China
| | - Min-Zhen Zhu
- Research Center for Brain Health, PazhouLab, Guangzhou 510330, China
| | - Si-Meng Liu
- Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China
| | - Rui-Chen Liu
- Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China
| | - Shuo Xu
- Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China
| | - Kiran Shehzadi
- Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China
| | - Hong-Le Ma
- Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China
| | - Ming-Jia Yu
- Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China
| | - Xin-Hong Zhu
- Research Center for Brain Health, PazhouLab, Guangzhou 510330, China
| | - Jian-Hua Liang
- Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China
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Wu YJ, Xiong JF, Zhan CN, Xu H. Gut microbiota alterations in colorectal adenoma-carcinoma sequence based on 16S rRNA gene sequencing: A systematic review and meta-analysis. Microb Pathog 2024; 195:106889. [PMID: 39197689 DOI: 10.1016/j.micpath.2024.106889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 08/12/2024] [Accepted: 08/25/2024] [Indexed: 09/01/2024]
Abstract
BACKGROUND Most sporadic colorectal cancers (CRC) develop through the adenoma-carcinoma sequence. While dysbiosis of the intestinal flora contributes to CRC's pathogenesis, precise microbial taxa closely associated with the colorectal adenoma-carcinoma sequence remain elusive. This meta-analysis aimed to summarize the features of intestinal flora in patients with AD and CRC. METHODS PubMed, Embase, Cochrane Library, and Web of Science were searched for case-control studies comparing the relative abundance of gut microbiota in the feces of patients with AD, CRC, and healthy controls (HC) from inception to January 2024. The weighted mean difference (WMD) with a 95 % confidence interval (CI) was used to display the results. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the entailed literature. Publication bias was evaluated with the Egger's and Begg's tests. RESULTS Eleven studies were included, involving 477 CRC patients, 628 AD patients, and 864 healthy controls. Compared with HC, the patients with AD had a significantly lower Chao 1 index (WMD = -30.17, 95 % CI [-41.10, -19.23], P < 0.001) and Shannon index (WMD = -0.11 95 % CI [-0.18, -0.04], P = 0.002). Compared with AD, the CRC patients had a significantly higher Chao1 index (WMD = 22.09, 95 % CI [7.59, 36.00], P = 0.003) and Shannon index (WMD = 0.08, 95 % CI [0.00, 0.15], P = 0.037). Enterobacteriaceae (WMD = 0.03 95 % CI [0.00,0.05], P = 0.047; WMD = 0.02 95 % CI [0.00,0.04], P = 0.027) significantly increased in the order of Control-AD-CRC, while that of Blautia (WMD = -0.00 95 % CI [-0.01, -0.00], P = 0.001; WMD = -0.00 95 % CI [-0.00, -0.00], P = 0.002) was reduced. Compared with HC, the relative abundance of Proteobacteria (WMD = 0.05 95 % CI [0.03,0.07], P < 0.001), Fusobacteria (WMD = 0.02 95 % CI [0.00,0.03], P = 0.042), Streptococcaceae (WMD = 0.03 95 % CI [0.01,0.05], P = 0.017), Prevotellaceae (WMD = 0.02 95 % CI [0.00,0.04], P = 0.040), and Escherichia-Shigella (WMD = 0.06 95 % CI [0.01, 0.11], P = 0.021) was enriched in the CRC group. The relative abundance of Alistipes (WMD = 0.00 95 % CI [0.00,0.01], P = 0.032) and Streptococcus (WMD = 0.00 95 % CI [0.00,0.00], P = 0.001) was increased in the AD vs HC. The relative abundance of Firmicutes (WMD = -0.07 95 % CI [-0.12, -0.03], P = 0.003), Bifidobacteria (WMD = -0.03 95 % CI [-0.05, -0.01], P = 0.016), and Klebsiella (WMD = -0.01 95 % CI [-0.01, -0.00], P = 0.001) was decreased in the CRC vs HC. Compared with AD, the relative abundance of Firmicutes (WMD = -0.04 95 % CI [-0.07, -0.02], P = 0.002), Peptostreptococcaceae (WMD = -0.03 95 % CI [-0.05, -0.00], P = 0.021), Lachnospiraceae (WMD = -0.04 95 % CI [-0.08,-0.00], P = 0.037), Ruminococcaceae (WMD = -0.06 95 % CI [-0.09,-0.03], P < 0.001), Faecalibacterium (WMD = -0.01 95 % CI [-0.02, -0.01], P = 0.001), and Lachnoclostridium (WMD = -0.02 95 % CI [-0.03, -0.00], P = 0.040) was decreased in the CRC group, while Proteobacteria (WMD = 0.04 95 % CI [0.02,0.05], P < 0.001) was increased. CONCLUSIONS The dysbiosis characterized by reduced levels of short-chain fatty acid (SCFA)-producing bacteria, decreased anti-inflammatory bacteria, increased pro-inflammatory bacteria, and an elevation of bacteria with cytotoxic effects damaging to DNA may represent the specific microbial signature of colorectal adenoma/carcinoma. Further research is required to elucidate the mechanisms by which gut dysbiosis leads to the progression from AD to CRC and to explore the potential of specific microbiota markers in clinical treatment and non-invasive screening.
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Affiliation(s)
- Yi-Jun Wu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jing-Fang Xiong
- Department of Geriatrics, Hangzhou Red Cross Hospital, Hangzhou, China
| | - Cheng-Nan Zhan
- Medical Service Community, Hangzhou Xiaoshan Hospital of TCM, Hangzhou, China
| | - Hong Xu
- Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, Hangzhou, China.
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Yue L, Luo J, Zhao C, Zhao J, Ye J, He K, Zou J. Oleanane triterpenoids with C-14 carboxyl group from Astilbe grandis inhibited LPS-induced macrophages activation by suppressing the NF- κB signaling pathway. Front Pharmacol 2024; 15:1413876. [PMID: 39148539 PMCID: PMC11324442 DOI: 10.3389/fphar.2024.1413876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 07/17/2024] [Indexed: 08/17/2024] Open
Abstract
Background Excessive inflammation poses significant risks to human physical and mental health. Astilbe grandis, a traditional Miao medicine, is renowned for its anti-inflammatory properties. However, the specific anti-inflammatory effects and mechanisms of many compounds within this plant remain unclear. This study aims to investigate the anti-inflammatory effects and mechanisms of two characteristic oleanane triterpenoids, 3α-acetoxyolean-12-en-27-oic acid (1) and 3β-acetoxyolean-12-en-27-oic acid (2), isolated from Astilbe grandis, using lipopolysaccharide (LPS)-induced Macrophages. Methods The anti-inflammatory effects and mechanisms of compounds 1 and 2 were investigated by establishing an LPS-induced inflammation model in RAW 264.7 cells and THP-1 cells. Nitric oxide (NO) levels were assessed using the Griess method. The concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β) were measured via enzyme-linked immunosorbent assay (ELISA). The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was determined using western blotting and quantitative real-time PCR (qRT-PCR). Additionally, the phosphorylation level of p65 in nuclear factor-kappa B (NF-κB) was assessed through western blotting. The nuclear translocation of NF-κB p65 was assessed through immunofluorescence staining. Finally, the binding affinity of the compounds to NF-κB p65 target was validated through molecular docking. Results Compounds 1 and 2 significantly inhibited the expression of NO, TNF-α, IL-6, IL-1β, COX-2, and iNOS in LPS-induced Macrophages. Mechanistically, they attenuated the activation of the NF-κB signaling pathway by downregulating the phosphorylation level and nuclear translocation of p65. Conclusion This study elucidates the anti-inflammatory activities and potential mechanism of the characteristic oleanane triterpenoids with C-14 carboxyl group, compounds 1 and 2, in LPS-induced Macrophages by inhibiting the NF-κB signaling pathway for the first time. These findings suggest that these two compounds hold promise as potential candidates for anti-inflammatory interventions in the future.
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Affiliation(s)
- Lan Yue
- School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jinfang Luo
- School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, China
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Chenliang Zhao
- School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jinfeng Zhao
- School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jianghai Ye
- School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Kang He
- School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Juan Zou
- School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, China
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Eisenbrand G, Buettner A, Diel P, Epe B, Först P, Grune T, Haller D, Heinz V, Hellwig M, Humpf HU, Jäger H, Kulling S, Lampen A, Leist M, Mally A, Marko D, Nöthlings U, Röhrdanz E, Spranger J, Steinberg P, Vieths S, Wätjen W, Hengstler JG. Commentary of the SKLM to the EFSA opinion on risk assessment of N-nitrosamines in food. Arch Toxicol 2024; 98:1573-1580. [PMID: 38573336 PMCID: PMC11106120 DOI: 10.1007/s00204-024-03726-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 04/05/2024]
Abstract
Dietary exposure to N-nitrosamines has recently been assessed by the European Food Safety Authority (EFSA) to result in margins of exposure that are conceived to indicate concern with respect to human health risk. However, evidence from more than half a century of international research shows that N-nitroso compounds (NOC) can also be formed endogenously. In this commentary of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG), the complex metabolic and physiological biokinetics network of nitrate, nitrite and reactive nitrogen species is discussed with emphasis on its influence on endogenous NOC formation. Pioneering approaches to monitor endogenous NOC have been based on steady-state levels of N-nitrosodimethylamine (NDMA) in human blood and on DNA adduct levels in blood cells. Further NOC have not been considered yet to a comparable extent, although their generation from endogenous or exogenous precursors is to be expected. The evidence available to date indicates that endogenous NDMA exposure could exceed dietary exposure by about 2-3 orders of magnitude. These findings require consolidation by refined toxicokinetics and DNA adduct monitoring data to achieve a credible and comprehensive human health risk assessment.
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Affiliation(s)
| | - Andrea Buettner
- Chair of Aroma and Smell Research, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestrasse 9, 91054, Erlangen, Germany
- Fraunhofer Institute for Process Engineering and Packaging IVV, Giggenhauser Strasse 35, 85354, Freising, Germany
| | - Patrick Diel
- Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany
| | - Bernd Epe
- Institute of Pharmaceutical and Biomedical Sciences, University of Mainz, Staudingerweg, 55128, Mainz, Germany
| | - Petra Först
- Food Process Engineering, TUM School of Life Sciences, Technical University of Munich, Weihenstephaner Berg 1, 85354, Freising, Germany
| | - Tillman Grune
- German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany
| | - Dirk Haller
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354, Freising, Germany
- ZIEL Institute for Food and Health, Technical University of Munich, Weihenstephaner Berg 1, 85354, Freising, Germany
| | - Volker Heinz
- DIL German Institute of Food Technology, Professor-von-Klitzing-Strasse 7, 49610, Quakenbrück, Germany
| | - Michael Hellwig
- Chair of Special Food Chemistry, Technical University Dresden, Bergstrasse 66, 01062, Dresden, Germany
| | - Hans-Ulrich Humpf
- Institute of Food Chemistry, University of Münster, Corrensstrasse 45, 48149, Münster, Germany
| | - Henry Jäger
- University of Natural Resources and Life Sciences, Gregor-Mendel-Strasse 33, 1180, Vienna, Austria
| | - Sabine Kulling
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Strasse 9, 76131, Karlsruhe, Germany
| | - Alfonso Lampen
- Risk Assessment Strategies, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany
| | - Marcel Leist
- Division for In Vitro Toxicology and Biomedicine, Department of Biology, University of Konstanz, Universitaetsstrasse 10, 78464, Constance, Germany
| | - Angela Mally
- Department of Toxicology, University of Würzburg, Versbacher Strasse 9, 97078, Würzburg, Germany
| | - Doris Marko
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Strasse 38-40, 1090, Vienna, Austria
| | - Ute Nöthlings
- Institute for Nutrition Research and Food Science, Rheinische Friedrich-Wilhelms-University Bonn, Fiedrich-Hirzebruch-Allee 7, 53115, Bonn, Germany
| | - Elke Röhrdanz
- Unit Reproductive and Genetic Toxicology, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger Allee 3, 53175, Bonn, Germany
| | - Joachim Spranger
- Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Pablo Steinberg
- Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-Und-Neu-Straße 9, 76131, Karlsruhe, Germany
| | - Stefan Vieths
- Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225, Langen, Germany
| | - Wim Wätjen
- Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany
| | - Jan G Hengstler
- Department of Toxicology, Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystr. 67, 44139, Dortmund, Germany.
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8
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Meng T, Liu C, Chen Y, Yu M, He J, Tan B, Fu X, He J, Xiao D. Dietary Chito-oligosaccharide attenuates LPS-challenged intestinal inflammation via regulating mitochondrial apoptotic and MAPK signaling pathway. Int Immunopharmacol 2024; 126:111153. [PMID: 37979451 DOI: 10.1016/j.intimp.2023.111153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 10/23/2023] [Accepted: 10/29/2023] [Indexed: 11/20/2023]
Abstract
To investigate the regulatory effects of Chito-oligosaccharide (COS) on the anti-oxidative, anti-inflammatory, and MAPK signaling pathways. A total of 40 28-day-old weaned piglets were randomly allotted to 4 equal groups [including the control group, lipopolysaccharide (LPS) group, COS group, and COS*LPS group]. On the morning of d 14 and 21, piglets were injected with saline or LPS. At 2 h post-injection, whole blood samples were collected on d 14 and 21, and small intestine and liver samples were collected and analyzed on d 21. The results showed that COS inhibited the LPS-induced increase of malondialdehyde (MDA) concentration and hepatic TNF-α cytokines. COS significantly increased the serum total antioxidant capability (T-AOC) value on d 14, and total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) activities in both serum and liver on d 21. Furthermore, it increased hepatic catalase (CAT) activity. COS also increased the LPS-induced decrease in serum IgG concentrations. Immunohistochemical analysis results showed that COS significantly increased the jejunal and ileal Caspase 3, and ileal CD4+ values challenged by LPS. Dietary COS decreased the LPS-induced jejunal and ileal BAX and CCL2 mRNA levels, markedly decreased ileal COX2 and SOD1 mRNA levels, while increasing ileal iNOS. Furthermore, COS significantly increased the LPS-induced jejunal and ileal p-P38 and MyD88, as well as jejunal P38, while it effectively suppressed jejunal JNK1, and jejunal and ileal JNK2, p-JNK1, and p-JNK2 protein expressions. These results demonstrated that COS could be beneficial by attenuating LPS-challenged intestinal inflammation via regulating mitochondrial apoptotic and MAPK signaling pathways.
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Affiliation(s)
- Tiantian Meng
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; College of Life Science, Xinyang Normal University, Xinyang 464000, China
| | - Chunming Liu
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Yulian Chen
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Manrong Yu
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Jianfu He
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Bihui Tan
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Xiaoqin Fu
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Jianhua He
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Dingfu Xiao
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China.
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9
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Al-Nattah S, Matkovic E, Schwalbe M, Matkowskyj KA. Pathologic Features of Esophageal and Gastric Malignancies. Cancer Treat Res 2024; 192:19-48. [PMID: 39212914 DOI: 10.1007/978-3-031-61238-1_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Esophageal cancer is the eighth most common cancer globally, affecting approximately 570,000 people worldwide and currently ranking sixth among cancer-related mortality (Uhlenhopp et al. in, Clin J Gastroenterol 13:1010-1021, 2020). The prognosis is poor as many patients present with locally incurable or metastatic disease. In spite of advancements in treatment, the overall 5-year survival rates are in the realm of 10% whereas the 5-year post-esophagectomy survival rates are in the realm of 15-40% [2]. The incidence rates vary dramatically worldwide, which can be attributed to demographic and socioeconomic factors. Although the vast majority of esophageal neoplasms arise from the epithelial layer and include squamous cell carcinoma (SCC) and adenocarcinoma (AC), a subset of neuroendocrine and soft tissue tumors can also occur in the esophagus. Several tasks are presented to the surgical pathologist when dealing with esophageal carcinoma that include rendering a diagnosis, classifying the histological type, and assessing prognostic factors. This narrative review aims to evaluate current literature on various esophageal neoplasms and highlight pathological factors that impact clinical decision making and prognosis.
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Affiliation(s)
- Sanaa Al-Nattah
- School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
- Quest Diagnostics, Las Vegas, NV, USA
| | - Eduard Matkovic
- School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
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Saijuntha W, Sithithaworn P, Wangboon C, Andrews RH, Petney TN. Liver Flukes: Clonorchis and Opisthorchis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1454:239-284. [PMID: 39008268 DOI: 10.1007/978-3-031-60121-7_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/16/2024]
Abstract
Clonorchis sinensis, Opisthorchis viverrini and O. felineus are liver flukes of human and animal pathogens occurring across much of Europe and Asia. Nevertheless, they are often underestimated compared to other, better known neglected diseases in spite of the fact that many millions of people are infected and hundreds of millions are at risk. This is possibly because of the chronic nature of the infection and disease and that it takes several decades prior to a life-threatening pathology to develop. Several studies in the past decade have provided more information on the molecular biology of the liver flukes which clearly lead to better understanding of parasite biology, systematics and population genetics. Clonorchiasis and opisthorchiasis are characterized by a chronic infection that induces hepatobiliary inflammation, especially periductal fibrosis, which can be detected by ultrasonography. These chronic inflammations eventually lead to cholangiocarcinoma (CCA), a usually fatal bile duct cancer that develops in some infected individuals. In Thailand alone, opisthorchiasis-associated CCA kills up to 20,000 people every year and is therefore of substantial public health importance. Its socioeconomic impacts on impoverished families and communities are considerable. To reduce hepatobiliary morbidity and CCA, the primary intervention measures focus on control and elimination of the liver fluke. Accurate diagnosis of liver fluke infections in both human and other mammalian, snail and fish intermediate hosts is important for achieving these goals. While the short-term goal of liver fluke control can be achieved by praziquantel chemotherapy, a comprehensive health education package targeting school children is believed to be more beneficial for a long-term goal/solution. It is recommended that transdisciplinary research or multisectoral control approach including one health and/or eco health intervention strategy should be applied to combat the liver flukes and hence contribute to reduction of CCA in endemic areas.
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Affiliation(s)
| | - Paiboon Sithithaworn
- Department of Parasitology and Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
| | - Chompunoot Wangboon
- School of Preclinical Sciences, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, Thailand
| | - Ross H Andrews
- CASCAP, Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Faculty of Medicine, St Mary's Campus, Imperial College London, London, UK
| | - Trevor N Petney
- CASCAP, Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Department of Paleontology and Evolution, State Museum of Natural History, Karlsruhe, Germany
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11
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Zeb F, Mehreen A, Naqeeb H, Ullah M, Waleed A, Awan UA, Haider A, Naeem M. Nutrition and Dietary Intervention in Cancer: Gaps, Challenges, and Future Perspectives. Cancer Treat Res 2024; 191:281-307. [PMID: 39133412 DOI: 10.1007/978-3-031-55622-7_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2024]
Abstract
The term "cancer" refers to the state in which cells in the body develop mutations and lose control over their replication. Malignant cancerous cells invade in various other tissue sites of the body. Chemotherapy, radiation, and surgery are the first-line modalities for the majority of solid cancers. These treatments work by mitigating the DNA damage of cancerous cells, but they can also cause harm to healthy cells. These side effects might be immediate or delayed, and they can cause a high rate of morbidity and mortality. Dietary interventions have a profound impact on whole-body metabolism, including immunometabolism and oncometabolism which have been shown to reduce cancer growth, progression, and metastasis in many different solid tumor models with promising outcomes in early phase clinical studies. Dietary interventions can improve oncologic or quality-of-life outcomes for patients that are undergoing chemotherapy or radiotherapy. In this chapter, we will focus on the impact of nutritional deficiencies, several dietary interventions and their proposed mechanisms which are used as a novel therapy in controlling and managing cancers.
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Affiliation(s)
- Falak Zeb
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Aqsa Mehreen
- Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan
| | - Huma Naqeeb
- Department of Clinical Nutrition, Shaukat Khanum Memorial Cancer Hospital, and Research Center, Peshawar, Pakistan
| | - Muneeb Ullah
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Afraa Waleed
- Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan
| | - Uzma Azeem Awan
- Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan
| | - Adnan Haider
- Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan
| | - Muhammad Naeem
- Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan.
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12
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Kolijn PM, Langerak AW. Immune dysregulation as a leading principle for lymphoma development in diverse immunological backgrounds. Immunol Lett 2023; 263:46-59. [PMID: 37774986 DOI: 10.1016/j.imlet.2023.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 07/28/2023] [Accepted: 08/10/2023] [Indexed: 10/01/2023]
Abstract
Lymphoma is a heterogeneous group of malignancies arising from lymphocytes, which poses a significant challenge in terms of diagnosis and treatment due to its diverse subtypes and underlying mechanisms. This review aims to explore the shared and distinct features of various forms of lymphoma predisposing conditions, with a focus on genetic, immunological and molecular aspects. While diseases such as autoimmune disorders, inborn errors of immunity and iatrogenic immunodeficiencies are biologically and immunologically distinct, each of these diseases results in profound immune dysregulation and a predisposition to lymphoma development. Interestingly, the increased risk is often skewed towards a particular subtype of lymphoma. Patients with inborn errors of immunity in particular present with extreme forms of lymphoma predisposition, providing a unique opportunity to study the underlying mechanisms. External factors such as chronic infections and environmental exposures further modulate the risk of lymphoma development. Common features of conditions predisposing to lymphoma include: persistent inflammation, recurrent DNA damage or malfunctioning DNA repair, impaired tumor surveillance and viral clearance, and dysregulation of fundamental cellular processes such as activation, proliferation and apoptosis. Our growing understanding of the underlying mechanisms of lymphomagenesis provides opportunities for early detection, prevention and tailored treatment of lymphoma development.
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Affiliation(s)
- P Martijn Kolijn
- Laboratory Medical Immunology, Department of Immunology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Anton W Langerak
- Laboratory Medical Immunology, Department of Immunology, Erasmus Medical Center, Rotterdam, the Netherlands.
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13
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Fu T, Gifford DR, Knight CG, Brockhurst MA. Eco-evolutionary dynamics of experimental Pseudomonas aeruginosa populations under oxidative stress. MICROBIOLOGY (READING, ENGLAND) 2023; 169:001396. [PMID: 37943284 PMCID: PMC10710836 DOI: 10.1099/mic.0.001396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 09/26/2023] [Indexed: 11/10/2023]
Abstract
Within-host environments are likely to present a challenging and stressful environment for opportunistic pathogenic bacteria colonizing from the external environment. How populations of pathogenic bacteria respond to such environmental challenges and how this varies between strains is not well understood. Oxidative stress is one of the defences adopted by the human immune system to confront invading bacteria. In this study, we show that strains of the opportunistic pathogenic bacterium Pseudomonas aeruginosa vary in their eco-evolutionary responses to hydrogen peroxide stress. By quantifying their 24 h growth kinetics across hydrogen peroxide gradients we show that a transmissible epidemic strain isolated from a chronic airway infection of a cystic fibrosis patient, LESB58, is much more susceptible to hydrogen peroxide than either of the reference strains, PA14 or PAO1, with PAO1 showing the lowest susceptibility. Using a 12 day serial passaging experiment combined with a mathematical model, we then show that short-term susceptibility controls the longer-term survival of populations exposed to subinhibitory levels of hydrogen peroxide, but that phenotypic evolutionary responses can delay population extinction. Our model further suggests that hydrogen peroxide driven extinctions are more likely with higher rates of population turnover. Together, these findings suggest that hydrogen peroxide is likely to be an effective defence in host niches where there is high population turnover, which may explain the counter-intuitively high susceptibility of a strain isolated from chronic lung infection, where such ecological dynamics may be slower.
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Affiliation(s)
- Taoran Fu
- Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PT, UK
| | - Danna R. Gifford
- Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PT, UK
| | - Christopher G. Knight
- Department of Earth and Environmental Sciences, School of Natural Sciences, Faculty of Science and Engineering, The University of Manchester, Manchester M13 9PT, UK
| | - Michael A. Brockhurst
- Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PT, UK
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14
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Kiełb P, Kaczorowski M, Kowalczyk K, Piotrowska A, Nowak Ł, Krajewski W, Chorbińska J, Dudek K, Dzięgiel P, Hałoń A, Szydełko T, Małkiewicz B. Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance. Cancers (Basel) 2023; 15:4578. [PMID: 37760548 PMCID: PMC10526823 DOI: 10.3390/cancers15184578] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 09/05/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Prostate cancer (PCa) is the second most frequently diagnosed cancer among men. The use of IL-17A and its receptor IL-17RA as prognostic markers for PCa has shown promising results. We analyzed the clinical data of 77 patients with PCa after radical prostatectomy with lymphadenectomy and lymph node metastasis (LN+). We assessed the expression levels of IL-17A and IL-17RA in cancer cells in prostate and, for the first time, also in LN+. Prostate IL-17A expression positively correlated with BMI (p = 0.028). In LN+, the expression of IL-17A was positively correlated with the percentage of affected lymph nodes (p = 0.006) and EAU risk groups (p = 0.001). Additionally, in the group with high IL-17A expression in LN+, the extracapsular extension (ECE) of the prostate was significantly more frequent (p = 0.033). Also, significant correlations with the level of IL-17RA expression was found-expression was higher in prostate than in LN+ (p = 0.009); in LN+, expression positively correlated with the EAU risk group (p = 0.045), and in the group of high expression in LN+ ECE of lymph nodes was detected significantly more often (p = 0.009). Our findings support the potential role of IL-17A and IL-17RA as PCa markers; however, further studies are needed to determine their roles and potential clinical applications.
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Affiliation(s)
- Paweł Kiełb
- University Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wroclaw, Poland; (K.K.); (Ł.N.); (W.K.); (J.C.); (T.S.)
| | - Maciej Kaczorowski
- Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-556 Wroclaw, Poland; (M.K.); (A.H.)
| | - Kamil Kowalczyk
- University Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wroclaw, Poland; (K.K.); (Ł.N.); (W.K.); (J.C.); (T.S.)
| | - Aleksandra Piotrowska
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland; (A.P.); (P.D.)
| | - Łukasz Nowak
- University Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wroclaw, Poland; (K.K.); (Ł.N.); (W.K.); (J.C.); (T.S.)
| | - Wojciech Krajewski
- University Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wroclaw, Poland; (K.K.); (Ł.N.); (W.K.); (J.C.); (T.S.)
| | - Joanna Chorbińska
- University Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wroclaw, Poland; (K.K.); (Ł.N.); (W.K.); (J.C.); (T.S.)
| | - Krzysztof Dudek
- Center for Statistical Analysis, Wroclaw Medical University, Marcinkowskiego 2-6, 50-368 Wroclaw, Poland;
| | - Piotr Dzięgiel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland; (A.P.); (P.D.)
| | - Agnieszka Hałoń
- Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-556 Wroclaw, Poland; (M.K.); (A.H.)
| | - Tomasz Szydełko
- University Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wroclaw, Poland; (K.K.); (Ł.N.); (W.K.); (J.C.); (T.S.)
| | - Bartosz Małkiewicz
- University Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wroclaw, Poland; (K.K.); (Ł.N.); (W.K.); (J.C.); (T.S.)
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15
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Phrompanya P, Suriyaruean N, Nantarat N, Saenphet S, Tragoolpua Y, Saenphet K. Biological properties of mucus from land snails ( Lissachatina fulica) and freshwater snails ( Pomacea canaliculata) and histochemical study of mucous cells in their foot. PeerJ 2023; 11:e15827. [PMID: 37583916 PMCID: PMC10424676 DOI: 10.7717/peerj.15827] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 07/11/2023] [Indexed: 08/17/2023] Open
Abstract
Background Mucus derived from many land snails has been extensively utilised in medicine and cosmetics, but some biological activities of the mucus need to be well documented. Nevertheless, most mucus is obtained from land snails, while mucus from freshwater snails has yet to be attended. Methods This study aims to determine and compare mucus's antioxidant and anti-inflammatory activities from the land snail Lissachatina fulica and the freshwater snail Pomacea canaliculata. ABTS, DPPH, reducing power and total antioxidant activity assays were used to evaluate the antioxidant capacity. Inhibition of nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells was performed to determine the anti-inflammatory activity. Additionally, the histochemical analysis of mucous cells in each snail foot was conducted to compare the distribution of mucous cells and types of mucins using periodic acid-Schiff and Alcian blue staining. Results Mucus from L. fulica and P. canaliculata exhibited antioxidant and anti-inflammatory activities in different parameters. L. fulica mucus has higher total antioxidant (44.71 ± 2.11 mg AAE/g) and nitric oxide inhibitory activities (IC50 = 9.67 ± 0.31 µg/ml), whereas P. canaliculata mucus has better-reducing power activity (43.63 ± 2.47 mg AAE/g) and protein denaturation inhibition (IC50 = 0.60 ± 0.03 mg/ml). Histochemically, both species' dorsal and ventral foot regions contained neutral and acid mucins in different quantities. In the dorsal region, the neutral mucins level in L. fulica (16.64 ± 3.46%) was significantly higher than that in P. canaliculata (11.19 ± 1.50%), while the acid mucins level showed no significant difference between species. Levels of both mucins in the ventral foot region of L. fulica (15.08 ± 3.97% and 10.76 ± 3.00%, respectively) were significantly higher than those of P. canaliculata (2.25 ± 0.48% and 2.71 ± 0.56%, respectively). This study revealed scientific evidence of the biological capacity of mucus from L. fulica and P. canaliculata as well as provided helpful information on the region of the foot which produces effective mucus.
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Affiliation(s)
- Phornphan Phrompanya
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
- Ph.D.’s Degree Program in Biology (International Program), Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
| | - Narinnida Suriyaruean
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
| | - Nattawadee Nantarat
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
| | - Supap Saenphet
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
| | - Yingmanee Tragoolpua
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
| | - Kanokporn Saenphet
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
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16
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Qiu H, Shao N, Liu J, Zhao J, Chen C, Li Q, He Z, Zhao X, Xu L. Amino acid metabolism in tumor: New shine in the fog? Clin Nutr 2023:S0261-5614(23)00184-X. [PMID: 37321900 DOI: 10.1016/j.clnu.2023.06.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 05/10/2023] [Accepted: 06/03/2023] [Indexed: 06/17/2023]
Abstract
Alterations in amino acid metabolism is closely related to the occurrence of clinical diseases. The mechanism of tumorigenesis is complex, involving the complicated relationship between tumor cells and immune cells in local tumor microenvironment. A series of recent studies have shown that metabolic remodeling is intimately related to tumorigenesis. And amino acid metabolic reprogramming is one of the important characteristics of tumor metabolic remodeling, which participates in tumor cells growth, survival as well as the immune cell activation and function in the local tumor microenvironment, thereby affecting tumor immune escape. Recent studies have further shown that controlling the intake of specific amino acids can significantly improve the effect of clinical intervention in tumors, suggesting that amino acid metabolism is gradually becoming one of the new promising targets of clinical intervention in tumors. Therefore, developing new intervention strategies based on amino acid metabolism has broad prospects. In this article, we review the abnormal changes in the metabolism of some typical amino acids, including glutamine, serine, glycine, asparagine and so on in tumor cells and summarize the relationship among amino acid metabolism, tumor microenvironment and the function of T cells. In particular, we discuss the current issues that need to be addressed in the related fields of tumor amino acid metabolism, aiming to provide a theoretical basis for the development of new strategies for clinical interventions in tumors based on amino acid metabolism reprogramming.
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Affiliation(s)
- Hui Qiu
- Special Key Laboratory of Gene Detection &Therapy of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi Guizhou 563000, China
| | - Nan Shao
- Special Key Laboratory of Gene Detection &Therapy of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi Guizhou 563000, China
| | - Jing Liu
- Special Key Laboratory of Gene Detection &Therapy of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi Guizhou 563000, China
| | - Juanjuan Zhao
- Special Key Laboratory of Gene Detection &Therapy of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi Guizhou 563000, China
| | - Chao Chen
- Special Key Laboratory of Gene Detection &Therapy of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi Guizhou 563000, China
| | - Qihong Li
- Special Key Laboratory of Gene Detection &Therapy of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi Guizhou 563000, China
| | - Zhixu He
- Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi Guizhou 563000, China; Special Key Laboratory of Gene Detection &Therapy of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China
| | - Xu Zhao
- School of Medicine, Guizhou University, Guizhou Guiyang, 550025 China; Special Key Laboratory of Gene Detection &Therapy of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China.
| | - Lin Xu
- Special Key Laboratory of Gene Detection &Therapy of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi Guizhou 563000, China.
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17
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Host-microbiota interactions and oncogenesis: Crosstalk and its implications in etiology. Microb Pathog 2023; 178:106063. [PMID: 36893903 DOI: 10.1016/j.micpath.2023.106063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 09/03/2022] [Accepted: 03/07/2023] [Indexed: 03/09/2023]
Abstract
A number of articles have discussed the potential of microbiota in oncogenesis. Several of these have evaluated the modulation of microbiota and its influence on cancer development. Even in recent past, a plethora of studies have gathered in order to understand the difference in microbiota population among different cancer and normal individuals. Although in majority of studies, microbiota mediated oncogenesis has been primarily attributed to the inflammatory mechanisms, there are several other ways through which microbiota can influence oncogenesis. These relatively less discussed aspects including the hormonal modulation through estrobolome and endobolome, production of cyclomodulins, and lateral gene transfer need more attention of scientific community. We prepared this article to discuss the role of microbiota in oncogenesis in order to provide concise information on these relatively less discussed microbiota mediated oncogenesis mechanisms.
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18
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Wani MY, Ganie NA, Wani DM, Wani AW, Dar SQ, Khan AH, A Khan N, Manzar MS, Dehghani MH. The phenolic components extracted from mulberry fruits as bioactive compounds against cancer: A review. Phytother Res 2023; 37:1136-1152. [PMID: 36592613 DOI: 10.1002/ptr.7713] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 11/02/2022] [Accepted: 11/26/2022] [Indexed: 01/03/2023]
Abstract
In Asia, mulberry has long been used to treat various infectious and internal ailments as a traditional medication. The compounds found in it have the potential to improve human health. Because there is no approved and defined evaluation procedure, it has not been formally or scientifically recognized. As a result of these investigations, a new frontier in traditional Chinese medicine has opened up, with the possibility of modernization, for the interaction between active components of mulberry and their biological activities. These studies have used current biotechnological technologies. For ages, mulberry has been used as an herbal remedy in Asia to cure various diseases and internal disorders. It has a high concentration of bioactive chemicals that benefit human health. The most abundant phenolic components extracted from white mulberry leaves are flavonoids (Kuwanons, Moracinflavans, Moragrols, and Morkotins), phenolic acids, alkaloids, and so forth. Flavonoids, benzofurans, chalcones, and alkaloids have been discovered to have cytotoxic effects on human cancer cell lines. There is growing evidence that mulberry fruits can potentially prevent cancer and other aging-related disorders due to their high concentration of bioactive polyphenolic-rich compounds and macro and micronutrients. Anthocyanins are rapidly absorbed after eating, arriving in the plasmalemma within 15-50 min and entirely removed after 6-8 hr. Due to a lack of an approved and consistent technique for its examination, it has yet to be formally or scientifically recognized. The mulberry plant is commercially grown for silkworm rearing, and less attention is paid to its bioactive molecules, which have a lot of applications in human health. This review paper discusses the phenolic compounds of white mulberry and black mulberry in detail concerning their role in cancer prevention.
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Affiliation(s)
- Mohd Younus Wani
- College of Temperate Sericulture, Mirgund, SKUAST-Kashmir, Shalimar, India
| | - N A Ganie
- College of Temperate Sericulture, Mirgund, SKUAST-Kashmir, Shalimar, India
| | - D M Wani
- Division of Entomology, SKUAST-Kashmir, Shalimar, India
| | - Ab Waheed Wani
- Division of Fruit Science, SKUAST-Kashmir, Shalimar, India
| | - S Q Dar
- Division of Fruit Science, SKUAST-Kashmir, Shalimar, India
| | - Afzal Husain Khan
- Civil Engineering Department, College of Engineering, Jazan University, Jizan, Saudi Arabia
| | - Nadeem A Khan
- Civil Engineering Department, Mewat Engineering College, New Delhi, India
| | - Mohammad Saood Manzar
- Department of Environmental Engineering, College of Engineering, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohammad Hadi Dehghani
- Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.,Institute for Environmental Research, Center for Solid Waste Research, Tehran University of Medical Sciences, Tehran, Iran
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19
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Rajai N, Ahmad A, Toya T, Sara JD, Herrmann J, Lerman LO, Lerman A. Coronary microvascular dysfunction is an independent predictor of developing cancer in patients with non-obstructive coronary artery disease. Eur J Prev Cardiol 2023; 30:209-216. [PMID: 35989450 PMCID: PMC10787540 DOI: 10.1093/eurjpc/zwac184] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 07/22/2022] [Accepted: 08/17/2022] [Indexed: 01/21/2023]
Abstract
AIMS Cardiovascular disease and cancer share common pathogenesis and risk factors. Coronary microvascular dysfunction (CMD), reflecting impaired coronary microvascular dilation in response to stress, is related to a higher risk of major cardiovascular events; however, its association with cancer has not been explored. METHODS AND RESULTS A retrospective study on 1042 patients with non-obstructive coronary artery diseases (NOCADs) was performed. Data regarding demographic, clinical history, diagnostic coronary reactivity test, and cancer occurrence were collected. Coronary microvascular dysfunction was defined as coronary flow reserve (the ratio of hyperaemic blood flow to resting blood flow) ≤2.5. Thirty-four per cent had CMD (67.4% female and the average age was 52.4 ± 12.2 years). Of 917 patients with no history of cancer, 15.5% developed cancer during follow-up [median of 9 (4, 16) years]. Kaplan-Meier analysis showed that CMD patients had lower cancer-free survival compared with those without CMD (log-rank P = 0.005). Cox proportional hazard analyses showed that after adjusting for age, sex, hypertension, diabetes, smoking, and glomerular filtration rate, CMD is independently associated with cancer [hazard ratio, 1.4; 95% confidence interval (CI), 1.09-2.04; P = 0.04]. The rate of major adverse cardiovascular events (MACE) was significantly higher in CMD patients compared with that in non-CMD patients who had a previous history of cancer [odds ratio (OR), 2.5; 95% CI, 1-6.2; P = 0.04] and those with no history of cancer (OR, 1.4; 95% CI, 1.01-1.9; P = 0.044). CONCLUSION Coronary microvascular dysfunction is associated with cancer incidence in patients presenting with NOCADs. This study emphasizes follow-up in patients with CMD to evaluate the risk of MACE as well as potential malignant diseases.
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Affiliation(s)
- Nazanin Rajai
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Ali Ahmad
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
- Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, USA
| | - Takumi Toya
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
- Division of Cardiology, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Jaskanwal D. Sara
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Joerg Herrmann
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Lilach O. Lerman
- Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, USA
| | - Amir Lerman
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
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20
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Russell TM, Richardson DR. The good Samaritan glutathione-S-transferase P1: An evolving relationship in nitric oxide metabolism mediated by the direct interactions between multiple effector molecules. Redox Biol 2023; 59:102568. [PMID: 36563536 PMCID: PMC9800640 DOI: 10.1016/j.redox.2022.102568] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 11/22/2022] [Accepted: 12/01/2022] [Indexed: 12/23/2022] Open
Abstract
Glutathione-S-transferases (GSTs) are phase II detoxification isozymes that conjugate glutathione (GSH) to xenobiotics and also suppress redox stress. It was suggested that GSTs have evolved not to enhance their GSH affinity, but to better interact with and metabolize cytotoxic nitric oxide (NO). The interactions between NO and GSTs involve their ability to bind and store NO as dinitrosyl-dithiol iron complexes (DNICs) within cells. Additionally, the association of GSTP1 with inducible nitric oxide synthase (iNOS) results in its inhibition. The function of NO in vasodilation together with studies associating GSTM1 or GSTT1 null genotypes with preeclampsia, additionally suggests an intriguing connection between NO and GSTs. Furthermore, suppression of c-Jun N-terminal kinase (JNK) activity occurs upon increased levels of GSTP1 or NO that decreases transcription of JNK target genes such as c-Jun and c-Fos, which inhibit apoptosis. This latter effect is mediated by the direct association of GSTs with MAPK proteins. GSTP1 can also inhibit nuclear factor kappa B (NF-κB) signaling through its interactions with IKKβ and Iκα, resulting in decreased iNOS expression and the stimulation of apoptosis. It can be suggested that the inhibitory activity of GSTP1 within the JNK and NF-κB pathways may be involved in crosstalk between survival and apoptosis pathways and modulating NO-mediated ROS generation. These studies highlight an innovative role of GSTs in NO metabolism through their interaction with multiple effector proteins, with GSTP1 functioning as a "good Samaritan" within each pathway to promote favorable cellular conditions and NO levels.
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Affiliation(s)
- Tiffany M Russell
- Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - Des R Richardson
- Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, 4111, Australia.
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21
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Gros B, Gómez Pérez A, Pleguezuelo M, Serrano Ruiz FJ, de la Mata M, Rodríguez-Perálvarez M. Helicobacter Species and Hepato-Biliary Tract Malignancies: A Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:595. [PMID: 36765552 PMCID: PMC9913828 DOI: 10.3390/cancers15030595] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 01/15/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
Helicobacter species may cause chronic inflammation of the biliary tract, but its relationship with cancer is controversial. We performed a systematic review and meta-analysis to evaluate the association between Helicobacter species and hepatobiliary tract malignancies. Twenty-six studies (4083 patients) were included in qualitative synthesis, and 18 studies (n = 1895 qualified for meta-analysis. All studies were at high-intermediate risk of bias. Most studies combined several direct microbiological methods, mostly PCR (23 studies), culture (8 studies), and/or CLOtest (5 studies). Different specimens alone or in combination were investigated, most frequently bile (16 studies), serum (7 studies), liver/biliary tissue (8 studies), and gastric tissue (3 studies). Patients with Helicobacter species infection had an increased risk of hepatobiliary tract malignancies (OR = 3.61 [95% CI 2.18-6.00]; p < 0.0001), with high heterogeneity in the analysis (I2 = 61%; p = 0.0003). This effect was consistent when Helicobacter was assessed in bile (OR = 3.57 [95% CI 1.73-7.39]; p = 0.0006), gastric tissue (OR = 42.63 [95% CI 5.25-346.24]; p = 0.0004), liver/biliary tissue (OR = 4.92 [95% CI 1.90-12.76]; p = 0.001) and serum (OR = 1.38 [95% CI 1.00-1.90]; p = 0.05). Heterogeneity was reduced in these sub-analyses (I2 = 0-27%; p = ns), except for liver/biliary tissue (I2 = 57%; p = 0.02). In conclusion, based on low-certainty data, Helicobacter species chronic infection is associated with a tripled risk of hepatobiliary tract malignancy. Prospective studies are required to delineate public health interventions.
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Affiliation(s)
- Beatriz Gros
- Department of Gastroenterology and Hepatology, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
- Maimonides Institute of Biomedical Research (IMIBIC), 14004 Córdoba, Spain
| | - Alberto Gómez Pérez
- Department of Gastroenterology and Hepatology, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
| | - María Pleguezuelo
- Department of Gastroenterology and Hepatology, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
- Maimonides Institute of Biomedical Research (IMIBIC), 14004 Córdoba, Spain
| | - Francisco Javier Serrano Ruiz
- Department of Gastroenterology and Hepatology, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
- Maimonides Institute of Biomedical Research (IMIBIC), 14004 Córdoba, Spain
| | - Manuel de la Mata
- Department of Gastroenterology and Hepatology, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
- Maimonides Institute of Biomedical Research (IMIBIC), 14004 Córdoba, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Manuel Rodríguez-Perálvarez
- Department of Gastroenterology and Hepatology, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
- Maimonides Institute of Biomedical Research (IMIBIC), 14004 Córdoba, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
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22
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Guo Q, Dong Z, Jiang L, Zhang L, Li Z, Wang D. Assessing Whether Morphological Changes in Axillary Lymph Node Have Already Occurred Prior to Metastasis in Breast Cancer Patients by Ultrasound. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58111674. [PMID: 36422213 PMCID: PMC9695007 DOI: 10.3390/medicina58111674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/12/2022] [Accepted: 11/16/2022] [Indexed: 11/22/2022]
Abstract
Background and Objectives: Whether the morphological changes in axillary lymph node (ALN) have occurred prior to metastasis remains unclear in breast cancer (BC) patients. The aim of this study is to investigate the influence of BC for the morphology of non-metastasis ALN (N−) and, further, to improve the performance of ultrasound (US) examination for metastasis ALN (N+). Materials and Methods: In this retrospective study, 653 patients with breast mass were enrolled and divided into normal group of 202 patients with benign breast tumor, N− group of 233 BC patients with negative ALN and N+ group of 218 BC patients with positive ALN. US features of ALN were evaluated and analyzed according to long (L) and short (S) diameter, the (L/S) axis ratio, cortical thickness, lymph node edge, replaced hilum and color Doppler flow imaging (CDFI). Results: ALN US features of short diameter, replaced hilum, cortical thickness and CDFI have significant statistical differences in N− group comparing with normal group and N+ group, respectively (p < 0.05). Conclusions: Therefore, BC can affect ALN and lead to US morphological changes whether lymph node metastasis is present, which reduces the sensitivity of axillary US. The combination of US and other examination methods should be applied to improve the diagnostic performance of N+.
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Affiliation(s)
- Qiang Guo
- Department of Ultrasound Medicine, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, China
- Correspondence: ; Tel.: +86-(189)-3081-7376
| | - Zhiwu Dong
- Department of Laboratory Medicine, Jinshan Branch of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 201599, China
| | - Lixin Jiang
- Department of Ultrasound in Medicine, Renji Hospital Affiliated to Shanghai Jiaotong University, Shanghai 201599, China
| | - Lei Zhang
- Department of Ultrasound Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
| | - Ziyao Li
- Department of Ultrasound Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
| | - Dongmo Wang
- Department of Ultrasound Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
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23
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Hong Y, Chen X, Li G. Prognostic factors in the treatment of gastric mucosal atypical hyperplasia by endoscopic submucosal dissection. BMC Surg 2022; 22:382. [DOI: 10.1186/s12893-022-01832-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 10/31/2022] [Indexed: 11/09/2022] Open
Abstract
Abstract
Background
Endoscopic submucosal dissection (ESD) is becoming increasingly popular as a treatment for precancerous lesions and early cancers of the stomach. However, there have been few studies on the factors associated with the recurrence of precancerous lesions after ESD.
Methods
To investigate the prognostic factors of gastric intraepithelial neoplasia, we retrospectively analyzed 115 patients who were treated with ESD between February 2018 and January 2020. Chi-square test and Fisher’s extract test were used to select factors for further investigation, and prognostic analysis was carried out with the Kaplan–Meier method and a Cox regression model.
Results
Platelet counts (P = 0.027) and albumin levels (P = 0.011) were both lower in patients with recurrence than in patients without recurrence of gastric mucosal atypical hyperplasia after ESD.
Conclusions
This study reveals that low platelet counts and albumin levels were probably unfavorable prognostic factors in mucosal atypical hyperplasia of the stomach.
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24
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Yousefi F, Asadikaram G, Karamouzian S, Abolhassani M, Pourghadamyari H, Moazed V, Khanjani N, Paydar P. Organochlorine and organophosphorus pesticides may induce brain cancer through oxidative stress. Toxicol Ind Health 2022; 38:717-732. [PMID: 36180968 DOI: 10.1177/07482337221125954] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
In this study, oxidative stress was investigated as the possible mechanism of action of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in primary brain tumors (PBT). The levels of seven OCP residues and enzymatic antioxidant biomarkers including erythrocyte acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and paraoxonase-1 (PON-1) along with non-enzymatic oxidative biomarkers including malondialdehyde (MDA), protein carbonyl (PC), total antioxidant capacity (TAC), and nitric oxide (NO) were measured in blood samples of 73 patients with PBT and 104 healthy controls. A significant association was found between farming activities and PBT (55% of patients were engaged in farming activities while 45% had no farming experience). The mean levels of β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 4,4 DDT, MDA, PC, NO, SOD, CAT, and GPx were significantly higher in PBT patients, whereas the levels of TAC, PON-1, and AChE were significantly lower in these patients. Regression analysis showed that PBT was correlated with β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, and 4,4 DDT. Based on these results, it can be concluded that OCPs and OPPs may play a role in PBT development through the formation of reactive oxygen species (ROS) and promoting oxidative stress.
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Affiliation(s)
- Fatemeh Yousefi
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman, Iran.,Department of Clinical Biochemistry, School of Medicine, 48463Kerman University of Medical Sciences, Kerman, Iran
| | - Gholamreza Asadikaram
- Department of Clinical Biochemistry, School of Medicine, 48463Kerman University of Medical Sciences, Kerman, Iran.,Neuroscience Research Center, Institute of Neuropharmacology, School of Medicine, 48463Kerman University of Medical Sciences, Kerman, Iran
| | - Saeid Karamouzian
- Department of Neurosurgery, School of Medicine, 48463Kerman University of Medical Sciences, Kerman, Iran
| | - Moslem Abolhassani
- Department of Clinical Biochemistry, School of Medicine, 48463Kerman University of Medical Sciences, Kerman, Iran
| | - Hossein Pourghadamyari
- Department of Clinical Biochemistry, School of Medicine, 48463Kerman University of Medical Sciences, Kerman, Iran
| | - Vahid Moazed
- Department of Hematology and Oncology, Faculty of Medicine, 48463Kerman University of Medical Sciences, Kerman, Iran
| | - Narges Khanjani
- Neurology Research Center, 48463Kerman University of Medical Sciences, Kerman, Iran
| | - Parisa Paydar
- Department of Clinical Biochemistry, School of Medicine, 48463Kerman University of Medical Sciences, Kerman, Iran
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25
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Rasheed MN, Hazim Hamoode R, Adnan Abdul-Jalil A. Association of glutathione S-transferase 1 (GSTP1) polymorphisms with Breast Cancer susceptibility. BIONATURA 2022. [DOI: 10.21931/rb/2022.07.03.42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Hereditary and environmental variables have a role in the development of breast cancer. This study aimed to examine the links between genetic Variations in the GSTP1 gene and Predisposition to breast cancer in an Iraqi population. The research included 40 Iraqi female breast cancer patients and 20 healthy volunteers. GSTP1-1695 A/G gene polymorphisms were investigated using polymerase chain reaction in Real-time (RT-PCR). The results showed the GSTP1 frequency of the wild GG genotypes was showed significantly (P<0.01) higher in healthy women in comparison with Breast cancer women (GG, 80% vs. 32.5%, respectively; furthermore, heterozygous AG genotypes were significantly higher in Breast cancer women in comparison with healthy women 42.5% vs. 20%, respectively at (P<0.01). While the mutant AA genotype (25%) in patient women appeared significantly (P<0.01) higher compared to healthy women (0.0%). Finally, we discovered a connection between GSTP1 polymorphisms and a higher chance of developing breast cancer in an Iraqi female population sample.
Keywords: glutathione S-transferase1, breast cancer, polymorphism.
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Affiliation(s)
- Marrib N. Rasheed
- University Of Baghdad / Institute of Genetic Engineering and Biotechnology for Postgraduate Studies, Iraq
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26
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Gautam R, Jo J, Acharya M, Maharjan A, Lee D, K C PB, Kim C, Kim K, Kim H, Heo Y. Evaluation of potential toxicity of polyethylene microplastics on human derived cell lines. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 838:156089. [PMID: 35605862 DOI: 10.1016/j.scitotenv.2022.156089] [Citation(s) in RCA: 88] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 05/16/2022] [Accepted: 05/17/2022] [Indexed: 05/14/2023]
Abstract
Microplastics bare of major concern for environmental conservation and animal welfare in recent years as its use has increased tremendously. Polyethylene microplastics (PE-MPs) are the most common microplastics and could get exposed to humans via different routes with oral>inhalation>dermal. Internalization of MPs through epithelial tissue could expose MPs to various cells such as dendritic cells, macrophages/monocytes, and/or T cells. In this study, we aimed at identifying the effects of two different sized (30.5 ± 10.5 and 6.2 ± 2.0 μm) PE-MPs on different human cell lines representing different tissues or cells that get exposed to MPs directly or indirectly. Six cell lines were cultured with different concentrations of PE-MPs and cell viability, intracellular reactive oxygen species (ROS), nitric oxide (NO), and cytokines were measured. PE-MPs did not substantially lower the cell viability of cells however highest concentration (1000 μg/mL) of both sized MPs slightly reduced cell viability in intestinal epithelial Caco-2 and lung epithelial A549 cells. Both sized PE-MPs induced higher NO in all the cell lines and upregulation of ROS generation was demonstrated at THP-1, Jurkat, and U937 immune cell lines. A pro-inflammatory cytokine response was seen in HaCaT keratinocyte cells when cultured with PE-MPs whereas the opposite effect was observed in THP-1 and U937 cells except with THP-1 cells cultured with larger-sized MPs. We found that the PE-MPs do not have the same effects on all kinds of cells and tissues exposed and the immune modulation is not necessarily inflammatory. Thus, this study gives insight into why more detailed studies focused on exposure routes and organ-specific effects of different MPs need to be carried out.
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Affiliation(s)
- Ravi Gautam
- Department of occupational health, College of Bio and Medical Sciences, Daegu Catholic University, Gyeongsan 38430, Republic of Korea.
| | - JiHun Jo
- Department of occupational health, College of Bio and Medical Sciences, Daegu Catholic University, Gyeongsan 38430, Republic of Korea
| | - Manju Acharya
- Department of occupational health, College of Bio and Medical Sciences, Daegu Catholic University, Gyeongsan 38430, Republic of Korea
| | - Anju Maharjan
- Department of occupational health, College of Bio and Medical Sciences, Daegu Catholic University, Gyeongsan 38430, Republic of Korea
| | - DaEun Lee
- Department of occupational health, College of Bio and Medical Sciences, Daegu Catholic University, Gyeongsan 38430, Republic of Korea
| | - Pramod Bahadur K C
- Graduate School Department of Toxicology, Daegu Catholic University, 38430 Gyeongsan, Republic of Korea
| | - ChangYul Kim
- Graduate School Department of Toxicology, Daegu Catholic University, 38430 Gyeongsan, Republic of Korea.
| | - KilSoo Kim
- Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Center, 41061 Daegu, Republic of Korea; College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea.
| | - HyoungAh Kim
- College of Medicine, Department of Preventive Medicine, The Catholic University of Korea, 06591 Seoul, Republic of Korea.
| | - Yong Heo
- Department of occupational health, College of Bio and Medical Sciences, Daegu Catholic University, Gyeongsan 38430, Republic of Korea; Graduate School Department of Toxicology, Daegu Catholic University, 38430 Gyeongsan, Republic of Korea.
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27
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Activation of Nrf2 by Esculetin Mitigates Inflammatory Responses through Suppression of NF-κB Signaling Cascade in RAW 264.7 Cells. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27165143. [PMID: 36014382 PMCID: PMC9412493 DOI: 10.3390/molecules27165143] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/10/2022] [Accepted: 08/10/2022] [Indexed: 11/19/2022]
Abstract
Inflammation is a major root of several diseases such as allergy, cancer, Alzheimer’s, and several others, and the present state of existing drugs provoked researchers to search for new treatment strategies. Plants are regarded to be unique sources of active compounds holding pharmacological properties, and they offer novel designs in the development of therapeutic agents. Therefore, this study aimed to explore the anti-inflammatory mechanism of esculetin in lipoteichoic acid (LTA)-induced macrophage cells (RAW 264.7). The relative expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) production and COX-2 expression were intensified in LTA-induced RAW cells. The phosphorylation status of mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, and c-Jun N-terminal kinase (JNK)) and nuclear factor kappa B (NF-κB) p65 were detected by using Western blot assay. The nuclear translocation of p65 was assessed by confocal microscopic image analysis. Esculetin significantly and concentration-dependently inhibited LTA-induced NO production and iNOS expression, but not COX-2 expression, in RAW cells. Esculetin was not effective in LTA-induced MAPK molecules (ERK, p38 and JNK). However, esculetin recovered LTA-induced IκBα degradation and NF-κB p65 phosphorylation. Moreover, esculetin at a higher concentration of 20 µM evidently inhibited the nuclear translocation of NF-κB p65. At the same high concentration, esculetin augmented Nrf2 expression and decreased DPPH radical generation in RAW 264.7 cells. This study exhibits the value of esculetin for the treatment of LTA-induced inflammation by targeting NF-κB signaling pathways via its antioxidant properties.
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28
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Kaur P, Arora S, Singh R. Isolation, characterization and biological activities of betulin from Acacia nilotica bark. Sci Rep 2022; 12:9370. [PMID: 35672366 PMCID: PMC9174266 DOI: 10.1038/s41598-022-13338-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 05/16/2022] [Indexed: 01/25/2023] Open
Abstract
Medicinal plants are in use of humankind since ancient and still they are playing an important role in effective and safer natural drug delivery systems. Acacia nilotica (native of Egypt) commonly known as babul belongs to family Fabaceae, widely spread in India, Sri Lanka and Sudan. Being a common and important plant, using in many ways from fodder (shoots and leaves to animals) to dyeing (leather coloration) to medicine (root, bark, leaves, flower, gum, pods). The present study is focused on investigating the natural chemistry and important biological activities of the plant. Employing bioassay guided fractionation coupled with TLC and column chromatography, a pure fraction named AN-10 was isolated from ethyl acetate fraction of crude methanol extract which identified as "Betulin (Lupan-3ß,28-diol)" by Liebermann-Burchard test and structure elucidation by UV-Vis, NMR and MS techniques. A battery of in vitro biological assays for antioxidant, anti-inflammatory and anticancer were performed and betulin showed excellent potential in all assays. It was found that the inhibitory potential in all assays were dose dependent manner and after a range of concentration, the activities get leveled off with no further increase in activity.
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Affiliation(s)
- Prabhjit Kaur
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143001, India.,Medicinal Plant Research Laboratory, Post Graduate Department of Botany, Khalsa College, Amritsar, Punjab, 143001, India
| | - Saroj Arora
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143001, India
| | - Rajbir Singh
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143001, India. .,Medicinal Plant Research Laboratory, Post Graduate Department of Botany, Khalsa College, Amritsar, Punjab, 143001, India.
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29
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Xing J, Fang Y, Zhang W, Zhang H, Tang D, Wang D. Bacterial driver-passenger model in biofilms: a new mechanism in the development of colorectal cancer. Clin Transl Oncol 2022; 24:784-795. [PMID: 35000132 DOI: 10.1007/s12094-021-02738-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 11/10/2021] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is a heterogeneous disease of the intestinal epithelium and ranks the third largest diagnosed malignancy in the world. Many studies have shown that the high risk of CRC is believed to be related to the formation of biofilms. To prove causation, it will be significant to decipher which specific bacteria in biofilms initiate and maintain CRC and fully describe their underlying mechanisms. Here we introduce a bacterial driver-passenger model. This model added a novel and compelling angle to the role of microorganisms, putting more emphasis on the transformation of bacterial composition in biofilms which play different roles in the development of CRC. In this model, bacterial drivers can initiate the formation of CRC through genotoxicity, while bacterial passengers maintain the CRC process through metabolites. On the basis of these pathogens, we further turned our attention to strategies that can inhibit and eradicate these pathogenic biofilms, with the aim of finding new ways to hinder colorectal carcinogenesis.
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Affiliation(s)
- J Xing
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, People's Republic of China
| | - Y Fang
- Department of Clinical Medical College, Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - W Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, People's Republic of China
| | - H Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, People's Republic of China
| | - D Tang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu Province Hospital, Yangzhou University, Yangzhou, 225001, People's Republic of China.
| | - D Wang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu Province Hospital, Yangzhou University, Yangzhou, 225001, People's Republic of China
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30
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Chen JJ, Cheng MJ, Lee TH, Kuo YH, Lu CT. Secondary Metabolites with Anti-Inflammatory from the Roots of Cimicifuga taiwanensis. Molecules 2022; 27:1657. [PMID: 35268758 PMCID: PMC8912030 DOI: 10.3390/molecules27051657] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/12/2022] [Accepted: 02/12/2022] [Indexed: 11/17/2022] Open
Abstract
The genus Cimicifuga is one of the smallest genera in the family Ranunculaceae. Cimicifugae Rhizoma originated from rhizomes of Cimicifuga simplex, and C. dahurica, C. racemosa, C. foetida, and C. heracleifolia have been used as anti-inflammatory, analgesic and antipyretic remedies in Chinese traditional medicine. Inflammation is related to many diseases. Cimicifuga taiwanensis was often used in folk therapy in Taiwan for inflammation. Phytochemical investigation and chromatographic separation of extracts from the roots of Cimicifuga taiwanensis has led to the isolation of six new compounds: cimicitaiwanins A-F (1-6, respectively). The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis (1D- and 2D-NMR, MS, and UV) and comparison with the literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Of the isolates, 3-6 exhibited potent anti-NO production activity, with IC50 values ranging from 6.54 to 24.58 μM, respectively, compared with that of quercetin, an iNOS inhibitor with an IC50 value of 34.58 μM. This is the first report on metabolite from the endemic Taiwanese plant-C. taiwanensis.
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Affiliation(s)
- Jih-Jung Chen
- Department of Pharmacy, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University (NYCU), Taipei 112, Taiwan;
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
| | - Ming-Jen Cheng
- Bioresource Collection and Research Center (BCRC), Food Industry Research and Development Institute (FIRDI), Hsinchu 300, Taiwan;
| | - Tzong-Huei Lee
- Institute of Fisheries Science, National Taiwan University, Taipei 10617, Taiwan;
| | - Yueh-Hsiung Kuo
- Department of Chemistry, National Taiwan University, Taipei 106, Taiwan;
- Department of Biotechnology, Asia University, Taichung 413, Taiwan
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan
- ChineseMedicine Research Center, ChinaMedical University, Taichung 404, Taiwan
| | - Chao-Tsen Lu
- Department of Chemistry, National Taiwan University, Taipei 106, Taiwan;
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31
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Are Inflammatory Bowel Disease and Colorectal Carcinoma Associated with Helicobacter pylori? A Prospective Study and Meta-analysis. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.1.75] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Observational studies regarding the correlation between colorectal carcinoma, inflammatory bowel disease and Helicobacter pylori infection are inconsistent. The present study aims to investigate the association between colorectal adenocarcinoma (CRA) and inflammatory bowel disease (IBD) with H. pylori status in 100 patients who have inflammatory bowel disease and colorectal carcinoma was confirmed disease by histological approach. Besides, a meta-analysis was performed of published studies, to evaluate the link between H. pylori infection and an increased risk of CRC and IBD. Among 67 cases with CRA and 33 cases with IBD, 59.7% and 51.5% were H. pylori positive; respectively. In the meta-analysis, thirty-nine articles were included, involving 13 231 cases with CRC and 2477 with IBD. The pooled odds ratio for CRC and IBD was 1.16 (95%CI = 0.73-1.82) and 0.42 (95%CI = 0.32-0.56); respectively. Our meta-analysis indicates that H. pylori is not associated with CRC.
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Matsuya Y, Hamada N, Yachi Y, Satou Y, Ishikawa M, Date H, Sato T. Inflammatory Signaling and DNA Damage Responses after Local Exposure to an Insoluble Radioactive Microparticle. Cancers (Basel) 2022; 14:cancers14041045. [PMID: 35205797 PMCID: PMC8869995 DOI: 10.3390/cancers14041045] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 02/09/2022] [Accepted: 02/15/2022] [Indexed: 12/30/2022] Open
Abstract
Simple Summary A cesium-bearing microparticle (Cs-BMP) is an insoluble radioactive microparticle possessing high specific radioactivity, which was discovered after the incident at the Fukushima nuclear power plant. Due to their insoluble nature, such Cs-BMPs are assumed to adhere in the long term to normal tissue, leading to chronic local exposure. However, radiation risk due to the intake of internal exposure to radioactive cesium is conventionally estimated from the organ dose given by uniform exposure to soluble cesium. As such, it is critical to clarify the normal tissue effects posed by heterogeneous exposure to Cs-BMPs. This in vitro study reports on the relationship between the inflammatory responses and DNA damage induction during local exposure to a Cs-BMP. Abstract Cesium-bearing microparticles (Cs-BMPs) can reach the human respiratory system after inhalation, resulting in chronic local internal exposure. We previously investigated the spatial distribution of DNA damage induced in areas around a Cs-BMP; however, the biological impacts have not been fully clarified due to the limited amount of data. Here, we investigated the inflammatory signaling and DNA damage responses after local exposure to a Cs-BMP in vitro. We used two normal human lung cell lines, i.e., lung fibroblast cells (WI-38) and bronchial epithelial cells (HBEC3-KT). After 24 h exposure to a Cs-BMP, inflammation was evaluated by immunofluorescent staining for nuclear factor κB (NF-κB) p65 and cyclooxygenase 2 (COX-2). The number of DNA double-strand breaks (DSBs) was also detected by means of phospholylated histone H2AX (γ-H2AX) focus formation assay. Cs-BMP exposure significantly increased NF-κB p65 and COX-2 expressions, which were related to the number of γ-H2AX foci in the cell nuclei. Compared to the uniform (external) exposure to 137Cs γ-rays, NF-κB tended to be more activated in the cells proximal to the Cs-BMP, while both NF-κB p65 and COX-2 were significantly activated in the distal cells. Experiments with chemical inhibitors for NF-κB p65 and COX-2 suggested the involvement of such inflammatory responses both in the reduced radiosensitivity of the cells proximal to Cs-BMP and the enhanced radiosensitivity of the cells distal from Cs-BMP. The data show that local exposure to Cs-BMP leads to biological effects modified by the NF-κB pathway, suggesting that the radiation risk for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.
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Affiliation(s)
- Yusuke Matsuya
- Nuclear Science and Engineering Center, Japan Atomic Energy Agency (JAEA), 2-4 Shirakata, Tokai 319-1195, Ibaraki, Japan;
- Correspondence:
| | - Nobuyuki Hamada
- Radiation Safety Unit, Biology and Environmental Chemistry Division, Sustainable System Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), 2-11-1 Iwado-kita, Komae 201-8511, Tokyo, Japan;
| | - Yoshie Yachi
- Graduate School of Health Sciences, Hokkaido University, Kita-12 Nishi-8, Kita-ku, Sapporo 060-0812, Hokkaido, Japan;
| | - Yukihiko Satou
- Collaborative Laboratories for Advanced Decommissioning Science (CLADS), Japan Atomic Energy Agency (JAEA), 790-1 Otsuka, Motooka Tomioka, Futaba 979-1151, Fukushima, Japan;
| | - Masayori Ishikawa
- Faculty of Health Sciences, Hokkaido University, Kita-12 Nishi-8, Kita-ku, Sapporo 060-0812, Hokkaido, Japan; (M.I.); (H.D.)
| | - Hiroyuki Date
- Faculty of Health Sciences, Hokkaido University, Kita-12 Nishi-8, Kita-ku, Sapporo 060-0812, Hokkaido, Japan; (M.I.); (H.D.)
| | - Tatsuhiko Sato
- Nuclear Science and Engineering Center, Japan Atomic Energy Agency (JAEA), 2-4 Shirakata, Tokai 319-1195, Ibaraki, Japan;
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Molina-García M, Malvehy J, Granger C, Garre A, Trullàs C, Puig S. Exposome and Skin. Part 2. The Influential Role of the Exposome, Beyond UVR, in Actinic Keratosis, Bowen's Disease and Squamous Cell Carcinoma: A Proposal. Dermatol Ther (Heidelb) 2022; 12:361-380. [PMID: 35112326 PMCID: PMC8850498 DOI: 10.1007/s13555-021-00644-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Indexed: 02/07/2023] Open
Abstract
Actinic keratosis (AK) is the main risk factor for the development of cutaneous invasive squamous cell carcinoma (SCC). It represents the first sign of severe chronic ultraviolet radiation exposure, which has a clear significant effect. Nevertheless, the skin is exposed to many other exposome factors which should be thoroughly considered. Our aim was to assess the impact of exposome factors other than ultraviolet radiation (UVR) on the etiopathology of AK and Bowen's disease (BD) and progression of AK to SCC and to design tailored prevention strategies. We performed an exhaustive literature search in September 2021 through PubMed on the impact of exposome factors other than UVR on AK, BD and SCC. We conducted several parallel searches combining terms of the following topics: AK, BD, SCC and microbiome, hormones, nutrition, alcohol, tobacco, viral infections, chemical contaminants and air pollution. Notably, skin microbiome studies have shown how Staphylococcus aureus infections are associated with AK and AK-to-SCC progression by the production of chronic inflammation. Nutritional studies have demonstrated how a caloric restriction in fat intake, oral nicotinamide and moderate consumption of wine significantly reduce the number of premalignant keratoses and SCC. Regarding lifestyle factors, both alcohol and smoking are associated with the development of SCC in a dose-dependent manner. Relevant environmental factors are viral infections and chemical contaminants. Human papillomavirus infections induce deregulation of cellular proliferation and are associated with AK, BD and SCC. In addition to outdoor jobs, occupations such as industrial processing and farming also increase the risk of developing keratoses and SCC. The exposome of AK will undoubtedly help the understanding of its etiopathology and possible progression to SCC and will serve as a basis to design tailored prevention strategies.
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Affiliation(s)
- Manuel Molina-García
- School of Medicine and Health Science, University of Barcelona (UB), 143 Casanova, 08036 Barcelona, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Dermatology Department, Melanoma Unit, Hospital Clinic, Universitat de Barcelona, 170 Villarroel, 08036 Barcelona, Spain
| | - Josep Malvehy
- School of Medicine and Health Science, University of Barcelona (UB), 143 Casanova, 08036 Barcelona, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Dermatology Department, Melanoma Unit, Hospital Clinic, Universitat de Barcelona, 170 Villarroel, 08036 Barcelona, Spain
- Centro de Investigación en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
| | - Corinne Granger
- Innovation and Development, ISDIN, 33 Provençals, 08019 Barcelona, Spain
| | - Aurora Garre
- Innovation and Development, ISDIN, 33 Provençals, 08019 Barcelona, Spain
| | - Carles Trullàs
- Innovation and Development, ISDIN, 33 Provençals, 08019 Barcelona, Spain
| | - Susana Puig
- School of Medicine and Health Science, University of Barcelona (UB), 143 Casanova, 08036 Barcelona, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Dermatology Department, Melanoma Unit, Hospital Clinic, Universitat de Barcelona, 170 Villarroel, 08036 Barcelona, Spain
- Centro de Investigación en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
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Ji M, Du L, Ma Z, Xie J, Huang Y, Wei X, Jiang X, Xu J, Yin R, Wang Y, Dai J, Jin G, Xu L, Zhu C, Hu Z, Ma H, Zhu M, Shen H. Circulating C-reactive protein increases lung cancer risk: Results from a prospective cohort of UK Biobank. Int J Cancer 2022; 150:47-55. [PMID: 34449869 DOI: 10.1002/ijc.33780] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 08/06/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023]
Abstract
Chronic inflammation has been associated with the development of lung cancer. In this study, we examined the association between C-reactive protein (CRP) and lung cancer in a prospective cohort study and used Mendelian randomization (MR) to clarify the causality. We included 420 977 participants from the UK Biobank (UKB) in the analyses; 1892 thereof were diagnosed with lung cancer during the follow-up. Hazards ratios (HRs) of CRP concentrations were estimated by Cox proportional hazard models and two approaches of MR analysis were performed. Besides, we added CRP concentrations to epidemiological model of lung cancer to evaluate its prediagnostic role through time-dependent receiver operating characteristic curve analysis. Elevated CRP levels were associated with a 22% increased lung cancer risk per 1 SD increase (HR = 1.22, 95% confidence interval [CI] = 1.18-1.26). Positive associations were observed in small cell lung cancer (HR = 1.21, 95% CI = 1.10-1.33), lung adenocarcinoma (HR = 1.17, 95% CI = 1.11-1.23) and lung squamous cell carcinoma (HR = 1.22, 95% CI = 1.14-1.31). No genetical association of circulating CRP levels and lung cancer risk was observed in MR analysis. When added to a risk model of lung cancer, CRP improved the performance of model as long as 8 years among current smokers (basic model: C-statistic = 0.78 [95% CI = 0.75-0.80]; CRP model: C-statistic = 0.79 [95% CI = 0.76-0.81]; Pnonadjusted = .003, Padjusted = .014). Our results did not support the causal association of circulating CRP with lung cancer risk. However, circulating CRP could be a prediagnostic marker of lung cancer as long as 8 years in advance for current smokers.
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Affiliation(s)
- Mengmeng Ji
- Department of Epidemiology, School of Public Health, Southeast University, Nanjing, China.,Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Lingbin Du
- Department of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Zhimin Ma
- Department of Epidemiology, School of Public Health, Southeast University, Nanjing, China.,Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Junxing Xie
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Yanqian Huang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xiaoxia Wei
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xiangxiang Jiang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Jing Xu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Rong Yin
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Yuzhuo Wang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Juncheng Dai
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Guangfu Jin
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Lin Xu
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Chen Zhu
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Department of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Zhibin Hu
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Hongxia Ma
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Meng Zhu
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Hongbing Shen
- Department of Epidemiology, School of Public Health, Southeast University, Nanjing, China.,Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Department of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Research Units of Cohort Study on Cardiovascular Diseases and Cancers, Chinese Academy of Medical Sciences, Beijing, China
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Hong S, Dia VP, Zhong Q. Synergistic anti-inflammatory activity of apigenin and curcumin co-encapsulated in caseins assessed with lipopolysaccharide-stimulated RAW 264.7 macrophages. Int J Biol Macromol 2021; 193:702-712. [PMID: 34717976 DOI: 10.1016/j.ijbiomac.2021.10.153] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/19/2021] [Accepted: 10/20/2021] [Indexed: 12/14/2022]
Abstract
Dietary polyphenols are potential anti-inflammatory agents, and their combinations with enhanced biological activities may lower toxicity and side effects. The objective of this work was to investigate the potential synergistic anti-inflammatory activities of apigenin and curcumin co-nanoencapsulated in sodium caseinate, with comparison to unencapsulated polyphenol combinations. Non-toxic concentrations of apigenin, curcumin, and their combinations in the free and co-encapsulated forms were studied in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Combinations of free polyphenols produced stronger inhibition of nitric oxide (NO) production, more significant at a higher proportion of curcumin, which was further enhanced after co-encapsulation. The enhanced reduction of NO was concomitant with the decreased expression of iNOS, the enhanced inhibition of pro-inflammatory cytokines of IL-6 and TNF-α, and the reduced production of intracellular reactive oxygen species. The potential multi-target effects and the enhanced solubility, proximity, and bioavailability of AP and CUR after co-encapsulation contributed to the synergistic activities. These results demonstrated that co-nanoencapsulation of apigenin and curcumin may enable the practical application utilizing the synergistic anti-inflammation effects to improve health.
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Affiliation(s)
- Shan Hong
- Department of Food Science, The University of Tennessee, Knoxville, TN, USA.
| | - Vermont P Dia
- Department of Food Science, The University of Tennessee, Knoxville, TN, USA
| | - Qixin Zhong
- Department of Food Science, The University of Tennessee, Knoxville, TN, USA.
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The Relationship of Glutathione- S-Transferase and Multi-Drug Resistance-Related Protein 1 in Nitric Oxide (NO) Transport and Storage. Molecules 2021; 26:molecules26195784. [PMID: 34641326 PMCID: PMC8510172 DOI: 10.3390/molecules26195784] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/21/2021] [Accepted: 09/21/2021] [Indexed: 12/18/2022] Open
Abstract
Nitric oxide is a diatomic gas that has traditionally been viewed, particularly in the context of chemical fields, as a toxic, pungent gas that is the product of ammonia oxidation. However, nitric oxide has been associated with many biological roles including cell signaling, macrophage cytotoxicity, and vasodilation. More recently, a model for nitric oxide trafficking has been proposed where nitric oxide is regulated in the form of dinitrosyl-dithiol-iron-complexes, which are much less toxic and have a significantly greater half-life than free nitric oxide. Our laboratory has previously examined this hypothesis in tumor cells and has demonstrated that dinitrosyl-dithiol-iron-complexes are transported and stored by multi-drug resistance-related protein 1 and glutathione-S-transferase P1. A crystal structure of a dinitrosyl-dithiol-iron complex with glutathione-S-transferase P1 has been solved that demonstrates that a tyrosine residue in glutathione-S-transferase P1 is responsible for binding dinitrosyl-dithiol-iron-complexes. Considering the roles of nitric oxide in vasodilation and many other processes, a physiological model of nitric oxide transport and storage would be valuable in understanding nitric oxide physiology and pathophysiology.
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Püschel J, Dubrovska A, Gorodetska I. The Multifaceted Role of Aldehyde Dehydrogenases in Prostate Cancer Stem Cells. Cancers (Basel) 2021; 13:4703. [PMID: 34572930 PMCID: PMC8472046 DOI: 10.3390/cancers13184703] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Revised: 08/27/2021] [Accepted: 09/13/2021] [Indexed: 02/06/2023] Open
Abstract
Cancer stem cells (CSCs) are the only tumor cells possessing self-renewal and differentiation properties, making them an engine of tumor progression and a source of tumor regrowth after treatment. Conventional therapies eliminate most non-CSCs, while CSCs often remain radiation and drug resistant, leading to tumor relapse and metastases. Thus, targeting CSCs might be a powerful tool to overcome tumor resistance and increase the efficiency of current cancer treatment strategies. The identification and isolation of the CSC population based on its high aldehyde dehydrogenase activity (ALDH) is widely accepted for prostate cancer (PCa) and many other solid tumors. In PCa, several ALDH genes contribute to the ALDH activity, which can be measured in the enzymatic assay by converting 4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) aminoacetaldehyde (BAAA) into the fluorescent product BODIPY-aminoacetate (BAA). Although each ALDH isoform plays an individual role in PCa biology, their mutual functional interplay also contributes to PCa progression. Thus, ALDH proteins are markers and functional regulators of CSC properties, representing an attractive target for cancer treatment. In this review, we discuss the current state of research regarding the role of individual ALDH isoforms in PCa development and progression, their possible therapeutic targeting, and provide an outlook for the future advances in this field.
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Affiliation(s)
- Jakob Püschel
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, 01309 Dresden, Germany;
| | - Anna Dubrovska
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, 01309 Dresden, Germany;
- National Center for Tumor Diseases (NCT), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01307 Dresden, Germany
- Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, 01328 Dresden, Germany
- German Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Ielizaveta Gorodetska
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, 01309 Dresden, Germany;
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Mazurek M, Rola R. The implications of nitric oxide metabolism in the treatment of glial tumors. Neurochem Int 2021; 150:105172. [PMID: 34461111 DOI: 10.1016/j.neuint.2021.105172] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 08/03/2021] [Accepted: 08/21/2021] [Indexed: 12/20/2022]
Abstract
Glial tumors are the most common intracranial malignancies. Unfortunately, despite such a high prevalence, patients' prognosis is usually poor. It is related to the high invasiveness, tendency to relapse and the resistance of tumors to traditional methods of treatment. An important link in the aspect of these issues may be nitric oxide (NO) metabolism. It is a very complex mechanism with multidirectional effects on the neoplastic process. Depending on the concentration axis, it can both exert pro-tumor action as well as contribute to the inhibition of tumorigenesis. The latest observations show that the control of its metabolism can be very helpful in the development of new methods of treating gliomas, as well as in increasing the effectiveness of the agents currently used. The influence of nitric oxide and nitric oxide synthase (NOS) activity on glioma stem cells seem to be of particular importance. The use of specific inhibitors may allow the reduction of tumor growth and its tendency to relapse. Another important feature of GSCs is their conditioning of glioma resistance to traditional forms of treatment. Recent studies have shown that modulation of NO metabolism can suppress this effect, preventing the induction of radio and chemoresistance. Moreover, nitric oxide is involved in the regulation of a number of immune mechanisms. Adequate modulation of its metabolism may contribute to the induction of an anti-tumor response in the patients' immune system.
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Affiliation(s)
- Marek Mazurek
- Chair and Department of Neurosurgery and Paediatric Neurosurgery, Medical University in Lublin, Poland.
| | - Radosław Rola
- Chair and Department of Neurosurgery and Paediatric Neurosurgery, Medical University in Lublin, Poland
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The Role of DNA Damage Response in Dysbiosis-Induced Colorectal Cancer. Cells 2021; 10:cells10081934. [PMID: 34440703 PMCID: PMC8391204 DOI: 10.3390/cells10081934] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/23/2021] [Accepted: 07/23/2021] [Indexed: 12/16/2022] Open
Abstract
The high incidence of colorectal cancer (CRC) in developed countries indicates a predominant role of the environment as a causative factor. Natural gut microbiota provides multiple benefits to humans. Dysbiosis is characterized by an unbalanced microbiota and causes intestinal damage and inflammation. The latter is a common denominator in many cancers including CRC. Indeed, in an inflammation scenario, cellular growth is promoted and immune cells release Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), which cause DNA damage. Apart from that, many metabolites from the diet are converted into DNA damaging agents by microbiota and some bacteria deliver DNA damaging toxins in dysbiosis conditions as well. The interactions between diet, microbiota, inflammation, and CRC are not the result of a straightforward relationship, but rather a network of multifactorial interactions that deserve deep consideration, as their consequences are not yet fully elucidated. In this paper, we will review the influence of dysbiosis in the induction of DNA damage and CRC.
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40
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Mughal MJ, Kwok HF. Multidimensional role of bacteria in cancer: Mechanisms insight, diagnostic, preventive and therapeutic potential. Semin Cancer Biol 2021; 86:1026-1044. [PMID: 34119644 DOI: 10.1016/j.semcancer.2021.06.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 05/28/2021] [Accepted: 06/08/2021] [Indexed: 02/08/2023]
Abstract
The active role of bacteria in oncogenesis has long been a topic of debate. Although, it was speculated to be a transmissible cause of cancer as early as the 16th-century, yet the idea about the direct involvement of bacteria in cancer development has only been explored in recent decades. More recently, several studies have uncovered the mechanisms behind the carcinogenic potential of bacteria which are inflammation, immune evasion, pro-carcinogenic metabolite production, DNA damage and genomic instability. On the other side, the recent development on the understanding of tumor microenvironment and technological advancements has turned this enemy into an ally. Studies using bacteria for cancer treatment and detection have shown noticeable effects. Therapeutic abilities of bioengineered live bacteria such as high specificity, selective cytotoxicity to cancer cells, responsiveness to external signals and control after ingestion have helped to overcome the challenges faced by conventional cancer therapies and highlighted the bacterial based therapy as an ideal approach for cancer treatment. In this review, we have made an effort to compile substantial evidence to support the multidimensional role of bacteria in cancer. We have discussed the multifaceted role of bacteria in cancer by highlighting the wide impact of bacteria on different cancer types, their mechanisms of actions in inducing carcinogenicity, followed by the diagnostic and therapeutic potential of bacteria in cancers. Moreover, we have also highlighted the existing gaps in the knowledge of the association between bacteria and cancer as well as the limitation and advantage of bacteria-based therapies in cancer. A better understanding of these multidimensional roles of bacteria in cancer can open up the new doorways to develop early detection strategies, prevent cancer, and develop therapeutic tactics to cure this devastating disease.
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Affiliation(s)
- Muhammad Jameel Mughal
- Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau
| | - Hang Fai Kwok
- Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau; MOE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, Macau.
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Elagan SK, Almalki SJ, Alharthi MR, Mohamed MS, EL-Badawy MF. Role of Bacteria in the Incidence of Common GIT Cancers: The Dialectical Role of Integrated Bacterial DNA in Human Carcinogenesis. Infect Drug Resist 2021; 14:2003-2014. [PMID: 34103947 PMCID: PMC8179827 DOI: 10.2147/idr.s309051] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 05/05/2021] [Indexed: 12/13/2022] Open
Abstract
Despite the wide medical knowledge about the direct role of many viruses in the pathogenesis of certain cancers, there is still ambiguity and hazy vision about the direct role of bacteria in cancer incidence. Understanding the role of bacteria in carcinogenesis is no longer a scientific luxury, but it has become an urgent and extremely important necessity to realize the pathogenesis of cancer caused by oncogenic bacteria as an attempt to overcome the oncogenic mechanisms exhibited by these oncogenic bacteria. This review shed the light on the indirect role of the host's inflammatory and immunological responses in the pathogenesis of bacteria-induced cancer. Also, this review discussed the indirect role of the bacterial toxins and virulence factors in the induction of common gastrointestinal cancers, such as gallbladder cancer (GBC), colorectal cancer (CRC), and gastric cancer (GC). Finally, this review dealt with the debate about the possibility of bacterial DNA integration into the human genome and cancer incidence.
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Affiliation(s)
- Sayed K Elagan
- Department of Mathematics and Statistics, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Saad J Almalki
- Department of Mathematics and Statistics, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - M R Alharthi
- Department of Mathematics and Statistics, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Mohamed S Mohamed
- Department of Mathematics and Statistics, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Mohamed F EL-Badawy
- Department of Microbiology and Immunology, Faculty of Pharmacy, University of Sadat City, Sadat City, 32958, Egypt
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The potential role of nontyphoidal salmonellosis in gastric cancer: a nationwide matched cohort study. Gastric Cancer 2021; 24:292-301. [PMID: 33130973 DOI: 10.1007/s10120-020-01132-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 09/28/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The research is to explore the association between nontyphoidal salmonellosis (NTS) and subsequent gastric cancer. METHODS We conducted a retrospective study by analyzing hospitalization dataset from the National Health Insurance Research Database in Taiwan. Patients aged 20 years and older with NTS (n = 9 097) admitted between January 1, 2000, and December 31, 2012, were enrolled and followed up until December 31, 2013. The primary outcome was the incidence of gastric cancer. Cox proportional hazards regression was used to estimate the risk of malignancy, accounting for the competing risk of death. In addition, we conducted a sensitivity analysis by propensity score matching and exclusion of malignancy within 1 year observation to minimize measurable confounding and protopathic bias. Negative controls were applied to examine the presence of possible unmeasured confounders in the study. RESULTS The study included 18 194 patients (9097 in each NTS and non-NTS group). The median follow-up time was 7 years. The incidence density rate of gastric cancer was 0.72 per 1000 person-years for the NTS group and 0.40 per 1000 person-years for the non-NTS group. The NTS group had a modestly higher risk of gastric cancer (aHR, 2.02; 95% CI 1.18-3.45) than the non-NTS group. The sensitivity analyses revealed consistent results. CONCLUSIONS Patients with NTS are associated with increased risk of subsequent gastric cancer compared with non-NTS patients. Future research is needed to examine whether NTS is parallel, reactive or causative to gastric cancer.
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Kotsiou OS, Gourgoulianis KI, Zarogiannis SG. The role of nitric oxide in pleural disease. Respir Med 2021; 179:106350. [PMID: 33662805 DOI: 10.1016/j.rmed.2021.106350] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 02/16/2021] [Accepted: 02/18/2021] [Indexed: 11/25/2022]
Abstract
Nitric oxide (NO) regulates various physiological and pathophysiological functions in the lungs. However, there is much less information about the effects of NO in the pleura. The present review aimed to explore the available evidence regarding the role of NO in pleural disease. NO, has a double-edged role in the pleural cavity. It is an essential signaling molecule mediating various physiological cell functions such as lymphatic drainage of the serous cavities, the immune response to intracellular multiplication of pathogens, and downregulation of neutrophil migration, but also induces genocytotoxic and mutagenic effects when present in excess. NO is implicated in the pathogenesis of asbestos-related or exudative pleural disease and mesothelioma. From a clinical point of view, the fraction of exhaled NO has been suggested as a potential non-invasive tool for the diagnosis of benign asbestos-related disorders. Under experimental conditions, NO-mimetics were found to attenuate hypoxia-induced therapy resistance in mesothelioma. Similarly, hybrid agents consisting of an NO donor coupled with a parent anti-inflammatory drug showed an enhancement of the anti-inflammatory activity of anti-inflammatory drugs. However, given the paucity of research work performed over the last years in this area, further research should be undertaken to establish reliable conclusions with respect to the feasibility of determining or targeting the NO signaling pathway for pleural disease diagnosis and therapeutic management.
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Affiliation(s)
- Ourania S Kotsiou
- Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41110, Larissa, Greece; Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece.
| | - Konstantinos I Gourgoulianis
- Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41110, Larissa, Greece
| | - Sotirios G Zarogiannis
- Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece
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Meng T, Xiao D, Muhammed A, Deng J, Chen L, He J. Anti-Inflammatory Action and Mechanisms of Resveratrol. Molecules 2021; 26:molecules26010229. [PMID: 33466247 PMCID: PMC7796143 DOI: 10.3390/molecules26010229] [Citation(s) in RCA: 359] [Impact Index Per Article: 89.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 12/31/2020] [Accepted: 12/31/2020] [Indexed: 02/07/2023] Open
Abstract
Resveratrol (3,4',5-trihy- droxystilbene), a natural phytoalexin polyphenol, exhibits anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. This phytoalexin is well-absorbed and rapidly and extensively metabolized in the body. Inflammation is an adaptive response, which could be triggered by various danger signals, such as invasion by microorganisms or tissue injury. In this review, the anti-inflammatory activity and the mechanism of resveratrol modulates the inflammatory response are examined. Multiple experimental studies that illustrate regulatory mechanisms and the immunomodulatory function of resveratrol both in vivo and in vitro. The data acquired from those studies are discussed.
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Affiliation(s)
- Tiantian Meng
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (T.M.); (A.M.); (J.D.)
| | - Dingfu Xiao
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (T.M.); (A.M.); (J.D.)
- Correspondence: (D.X.); (J.H.)
| | - Arowolo Muhammed
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (T.M.); (A.M.); (J.D.)
| | - Juying Deng
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (T.M.); (A.M.); (J.D.)
| | - Liang Chen
- Huaihua Institute of Agricultural Sciences, No.140 Yingfeng East Road, Hecheng District, Huaihua 418000, China;
| | - Jianhua He
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (T.M.); (A.M.); (J.D.)
- Correspondence: (D.X.); (J.H.)
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Shao J, Yan ZY, Tang M, Huang CH, Sheng ZG, Chen J, Shao B, Zhu BZ. Potent oxidation of DNA by Ru(ii) tri(polypyridyl) complexes under visible light irradiation via a singlet oxygen-mediated mechanism. Inorg Chem Front 2021. [DOI: 10.1039/d0qi01518k] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The irradiation of Ru(ii) tri(polypridyl) complexes with visible light can induce potent oxidation of DNA mediated by 1O2via a type II photosensitization mechanism.
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Affiliation(s)
- Jie Shao
- State Key Laboratory of Environmental Chemistry and Eco-toxicology
- Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences
- the Chinese Academy of Sciences
- Beijing 100085
- PR China
| | - Zhu-Ying Yan
- State Key Laboratory of Environmental Chemistry and Eco-toxicology
- Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences
- the Chinese Academy of Sciences
- Beijing 100085
- PR China
| | - Miao Tang
- State Key Laboratory of Environmental Chemistry and Eco-toxicology
- Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences
- the Chinese Academy of Sciences
- Beijing 100085
- PR China
| | - Chun-Hua Huang
- State Key Laboratory of Environmental Chemistry and Eco-toxicology
- Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences
- the Chinese Academy of Sciences
- Beijing 100085
- PR China
| | - Zhi-Guo Sheng
- State Key Laboratory of Environmental Chemistry and Eco-toxicology
- Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences
- the Chinese Academy of Sciences
- Beijing 100085
- PR China
| | - Jing Chen
- State Key Laboratory of Environmental Chemistry and Eco-toxicology
- Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences
- the Chinese Academy of Sciences
- Beijing 100085
- PR China
| | - Bo Shao
- State Key Laboratory of Environmental Chemistry and Eco-toxicology
- Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences
- the Chinese Academy of Sciences
- Beijing 100085
- PR China
| | - Ben-Zhan Zhu
- State Key Laboratory of Environmental Chemistry and Eco-toxicology
- Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences
- the Chinese Academy of Sciences
- Beijing 100085
- PR China
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A Comparative Study on Phenolic Content, Antioxidant Activity and Anti-Inflammatory Capacity of Aqueous and Ethanolic Extracts of Sorghum in Lipopolysaccharide-Induced RAW 264.7 Macrophages. Antioxidants (Basel) 2020; 9:antiox9121297. [PMID: 33353009 PMCID: PMC7767246 DOI: 10.3390/antiox9121297] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 12/14/2020] [Accepted: 12/15/2020] [Indexed: 11/17/2022] Open
Abstract
Sorghum is an important cereal with diverse phenolic compounds that have potential health promoting benefits. The current study comparatively characterized the phenolic contents of two novel black-seeded sorghum lines (SC84 and PI570481) using different extraction systems (water, ethanol and their acidified counterparts) and evaluated their antioxidant and anti-inflammatory activities. Phenolic compositions were determined by spectrophotometric assays and HPLC analysis. Antioxidant activities were assessed by radical scavenging effects on nitric oxide (NO) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, and the oxygen radical absorbance capacity (ORAC). Anti-inflammatory capacity was estimated by measuring levels of pro-inflammatory markers produced by lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Results showed that effects of solvent types and HCl on extraction efficiency differed among phenolic compounds and sorghum samples. Tannins were the most dominant polyphenols in the studied extracts (11.11-136.11 mg epicatechin equivalent/g sorghum). Sorghum extracts exerted more potent scavenging activity on DPPH than NO radicals. In LPS-activated RAW264.7 cells, sorghum extracts dose-dependently inhibited the production of NO, interleukin-6 (IL-6), and intracellular reactive oxygen species (ROS), with ethanolic extracts showing greater anti-inflammatory activity. Positive correlations were noted between tannin content and DPPH radical scavenging activity, and anti-inflammatory capacity. These results suggest the potential role of tannin-rich sorghum extracts against inflammation and associated diseases.
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Anti-Inflammatory Flavonolignans from Triticum aestivum Linn. Hull. APPLIED SCIENCES-BASEL 2020. [DOI: 10.3390/app10238656] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Wheat (Triticum aestivum Linn.; Poaceae) is a very common and important food grain and ranks second in total cereal crop production. A large amount of wheat hull is produced after threshing that, as the non-food part of wheat, is agro-waste, accounting for 15~20% of the wheat. This study aimed at biologically and phytochemically investigating wheat hull for its valorization as a by-product. In our ongoing search for natural product-derived anti-inflammatory agents, T. aestivum hull was evaluated for its nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated RAW 264.7 cells, and the phytochemical investigation of the ethyl acetate fraction showing inhibitory effect led to the isolation of a flavone (1) and seven flavonolignans (2–8). Compounds 2–8 have not yet been isolated from Triticum species. All compounds were evaluated for their LPS-induced NO production inhibition, and 1, 2, 4, 6, and 8 exhibited inhibitory effects with IC50 values ranging from 24.14 to 58.95 μM. These results suggest the potential of using T. aestivum hull as a source for producing anti-inflammatory components, enhancing its valorization as a by-product.
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Rosanortriterpenes A-B, Two Promising Agents from Rosa laevigata var. leiocapus, Alleviate Inflammatory Responses and Liver Fibrosis in In Vitro Cell Models. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:8872945. [PMID: 33224259 PMCID: PMC7673933 DOI: 10.1155/2020/8872945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 10/18/2020] [Accepted: 10/24/2020] [Indexed: 11/18/2022]
Abstract
Rosanortriterpenes A–B (RTA and RTB), two nortriterpenoids, are characteristic constituents in the fruits of Rosa laevigata var. leiocapus. However, pharmacological studies on these compounds are still scarce. In the present study, we aim to investigate the anti-inflammatory mechanisms associated with the effects of RTA–B in RAW264.7 macrophages and LO2 cells by detecting cell viabilities, nitric oxide (NO) production, tumour necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) production. Simultaneously, the anti-inflammatory action mechanisms of these two compounds were illustrated through western blot assay. Besides, the antihepatic fibrosis activities of these compounds have also been explored. The results demonstrated that RTA and RTB inhibited the production of NO, TNF-α, and IL-6 and suppressed liver fibrosis. RTA and RTB treatment also greatly inhibited the activation of NF-kappaB (NF-κB) pathway. Our study confirmed the promising anti-inflammatory and anti-liver fibrosis actions of RTA–B, suggesting that they might be developed as alternative and promising drugs for the treatment of hepatic inflammatory and fibrotic diseases.
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Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects. Eur J Med Chem 2020; 212:113028. [PMID: 33248848 DOI: 10.1016/j.ejmech.2020.113028] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/11/2020] [Accepted: 11/13/2020] [Indexed: 11/22/2022]
Abstract
Inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapeutic approach in the treatment of inflammation. Driven by the in-house database product lead 1, a hybridization strategy was utilized for the design of a series of novel benzo [d]thiazol derivatives. To our delight, D016, a byproduct of compound 9, was obtained with an extraordinarily low IC50 value of 0.1 nM but poor physical and chemical properties. After removal of a non-essential urea moiety or replacement of the urea group by an amide group, compounds 15a, 17p, and 18d were identified as promising sEH inhibitors, and their molecular binding modes to sEH were constructed. Furthermore, compounds 15a and 18d exhibited more effective in vivo anti-inflammatory effect than t-AUCB in carrageenan-induced mouse paw edema. Compound 15a also showed moderate metabolic stability with a half-time of 34.7 min. Although 18d was unstable in rat liver microsomes, it might be a "prodrug". In conclusion, this study could provide valuable insights into discovery of new sEH inhibitors, and compounds 15a and 18d were worthy of further development as potential drug candidates to treat inflammation.
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50
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Lee MR, Kim JE, Park JJ, Choi JY, Song BR, Choi YW, Kim DS, Kim KM, Song HK, Hwang DY. Protective role of fermented mulberry leave extract in LPS‑induced inflammation and autophagy of RAW264.7 macrophage cells. Mol Med Rep 2020; 22:4685-4695. [PMID: 33174019 PMCID: PMC7646855 DOI: 10.3892/mmr.2020.11563] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 05/18/2020] [Indexed: 12/13/2022] Open
Abstract
Mulberry leaves have antioxidant activity and anti‑inflammatory effects in several types of cells. However, the efficacy of mulberry leaves fermented with Cordyceps militaris remains unknown. Therefore, the present study aimed to investigate whether the ethanol extracts of mulberry leaves fermented with C. militaris (EMfC) can prevent lipopolysaccharide (LPS)‑induced inflammation and autophagy in macrophages. To achieve this, RAW264.7 cells pretreated with three different dose of EMfCs were subsequently stimulated with LPS, and examined for alterations in the regulatory factors of inflammatory responses and key parameters of the autophagy signaling pathway. EMfC treatment inhibited the generation of reactive oxidative species; however, significant activity was observed for 2,2‑diphenyl‑1‑picrylhydrazyl (DPPH) radical scavenging (IC50=579.6703 mg/ml). Most regulatory factors in inflammatory responses were significantly inhibited following treatment with EMfC, without any significant cellular toxicity. EMfC‑treated groups exhibited marked suppression of nitrogen oxide (NO) levels, mRNA expression levels of iNOS/COX‑2, levels of all inflammatory cytokines (TNF‑α, IL‑1β and IL‑6) and phosphorylation of MAPK members, as well as recovery of cell cycle progression. Furthermore, similar effects were observed in the LPS‑induced autophagy signaling pathway of RAW264.7 cells. The expression levels of microtubule‑associated protein 1A/1B‑light chain 3 (LC3) and Beclin exhibited a dose‑dependent decrease in the EMfC+LPS‑treated groups compared with in the Vehicle+LPS‑treated group, whereas the phosphorylation of PI3K and mTOR were enhanced in a dose‑dependent manner in the same groups. Overall, the results of the present study provide evidence that exposure to EMfC protects against LPS‑induced inflammation and autophagy in RAW264.7 cells. These results indicated that EMfC is a potential candidate for treatment of inflammatory diseases.
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Affiliation(s)
- Mi Rim Lee
- Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea
| | - Ji Eun Kim
- Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea
| | - Jin Ju Park
- Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea
| | - Jun Young Choi
- Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea
| | - Bo Ram Song
- Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea
| | - Young Whan Choi
- Department of Horticultural Life Sciences, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea
| | - Dong-Seob Kim
- Department of Food Science and Technology, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea
| | - Kyung Mi Kim
- Life Science Research Institute, Novarex Co., Ltd., Chungju 28126, Republic of Korea
| | - Hyun Keun Song
- Central Research Institute, Kinesciences Co., Seoul 02850, Republic of Korea
| | - Dae Youn Hwang
- Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea
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