59 results on '"Nguyen BC"'
Search Results
2. A global database of sea surface dimethylsulfide (DMS) measurements and a procedure to predict sea surface DMS as a function of latitude, longitude, and month
- Author
-
Kettle, Aj, Andreae, Mo, Amouroux, D, Andreae, Tw, Bates, Ts, Berresheim, H, Bingemer, H, Boniforti, R, Curran, Maj, Ditullio, Gr, Helas, G, Jones, Gb, Keller, Md, Kiene, Rp, Leck, C, Levasseur, Marie, Malin, G, Maspero, M, Matrai, P, Mctaggart, Ar, Mihalopoulos, N, Nguyen, Bc, Novo, A, Putaud, Jp, Rapsomanikis, S, Roberts, G, Schebeske, G, Sharma, S, Simo, R, Staubes, R, Turner, S, Uher, G, Kettle, Aj, Andreae, Mo, Amouroux, D, Andreae, Tw, Bates, Ts, Berresheim, H, Bingemer, H, Boniforti, R, Curran, Maj, Ditullio, Gr, Helas, G, Jones, Gb, Keller, Md, Kiene, Rp, Leck, C, Levasseur, Marie, Malin, G, Maspero, M, Matrai, P, Mctaggart, Ar, Mihalopoulos, N, Nguyen, Bc, Novo, A, Putaud, Jp, Rapsomanikis, S, Roberts, G, Schebeske, G, Sharma, S, Simo, R, Staubes, R, Turner, S, and Uher, G
- Abstract
A database of 15,617 point measurements of dimethylsulfide (DMS) in surface waters along with lesser amounts of data for aqueous and particulate dimethylsulfoniopropionate concentration, chlorophyll concentration, sea surface salinity and temperature, and wind speed has been assembled. The database was processed to create a series of climatological annual and monthly 1 degrees x1 degrees latitude-longitude squares of data. The results were compared to published fields of geophysical and biological parameters. No significant correlation was found between DMS and these parameters, and no simple algorithm could be found to create monthly fields of sea surface DMS concentration based on these parameters. Instead, an annual map of sea surface DMS was produced using an algorithm similar to that employed by Conkright et al. [1994]. In this approach, a first-guess field of DMS sea surface concentration measurements is created and then a correction to this field is generated based on actual measurements. Monthly sea surface grids of DMS were obtained using a similar scheme, but the sparsity of DMS measurements made the method difficult to implement. A scheme was used which projected actual data into months of the year where no data were otherwise present.
- Published
- 1999
- Full Text
- View/download PDF
3. Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation
- Author
-
Karine Lefort, Dennis R. Roop, Caterina Missero, G. Paolo Dotto, Maranke I. Koster, Dario Antonini, Anna Mandinova, Zhuo Zhang, Bach Cuc Nguyen, Giusy Della Gatta, Alice Tommasi di Vignano, Jan Kitajewski, Jian Wang, Vikram Devgan, Giovanna Chiorino, Nguyen, Bc, Lefort, K, Mandinova, A, Antonini, Dario, Devgan, V, Della Gatta, G, Koster, Mi, Zhang, Z, Wang, J, Tommasi di Vignano, A, Kitajewski, J, Chiorino, G, Roop, Dr, Missero, Caterina, and Dotto, Gp
- Subjects
Keratinocytes ,Cellular differentiation ,Notch signaling pathway ,Biology ,Cell fate determination ,DNA-binding protein ,Mice ,Genetics ,medicine ,Animals ,Humans ,RNA, Small Interfering ,Receptor, Notch1 ,Promoter Regions, Genetic ,Transcription factor ,DNA Primers ,Base Sequence ,Tumor Suppressor Proteins ,Cell Differentiation ,Cell cycle ,Molecular biology ,Cell biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,Trans-Activators ,IRF7 ,sense organs ,Keratinocyte ,Developmental Biology ,Research Paper ,Transcription Factors - Abstract
Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.
- Published
- 2006
4. Vietnam Association of Gastroenterology consensus for the diagnosis and treatment of functional dyspepsia.
- Author
-
Tran KT, Mai BH, Ta L, Dao LV, Tran HV, Tran MK, Quach DT, Vu KT, Ho QDD, Vu KV, Tran TT, Pham TT, Trinh DT, Nguyen VT, Tran TV, Duong TH, Bui HH, Nguyen VT, Nguyen TT, Nguyen TD, Nguyen BC, Phan HQ, Nguyen LC, Nguyen TL, Dao HV, Thai KD, Phan NT, Le NV, Le LT, Vo MH, Le TT, Ho PT, Le QD, Tran PP, and Dau QL
- Subjects
- Humans, Vietnam, Consensus, Societies, Medical, Gastroenterology standards, Dyspepsia diagnosis, Dyspepsia therapy, Delphi Technique
- Abstract
Abstract: Functional dyspepsia (FD) is a common disorder in clinical practice. It is necessary to rule out physical causes to diagnose this condition. However, the diagnosis is challenging particularly in resource-limited areas. The aim of this consensus is to update international and regional guidelines on the management of FD. The consensus panel included 32 experts from major Vietnamese universities and institutes. This consensus study was conducted using the Delphi method. The grade of recommendation and level of evidence were assessed using the Grading of Recommendations, Assessment, Development, and Evalua-tion system. The consensus level was defined as ≥80% for agreement on the proposed statements. The expert panel approved 14 statements after two rounds of voting, which were related to two sections: (1) diagnostic tests for FD and (2) treatment of FD. This consensus is expected to help physicians in identifying and managing FD appropriately in daily clinical practice and to contribute FD data to Asian regions.
- Published
- 2024
- Full Text
- View/download PDF
5. Essential Oil from Vietnamese Peperomia leptostachya Hook. & Arn. (Piperaceae): Chemical Composition, Antioxidant, Anti-Inflammatory, Cytotoxic Activities, and In Silico Analysis.
- Author
-
Nguyen HM, Pham TV, Vo HQ, Nguyen HT, Nguyen LTK, Nguyen BC, Chung KL, and Ho DV
- Subjects
- Animals, Mice, Computer Simulation, Gas Chromatography-Mass Spectrometry, Nitric Oxide metabolism, Plant Leaves chemistry, RAW 264.7 Cells, Vietnam, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents chemistry, Antioxidants pharmacology, Antioxidants chemistry, Oils, Volatile pharmacology, Oils, Volatile chemistry, Peperomia chemistry
- Abstract
This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of Peperomia leptostachya leaf oil. A yellow oil was obtained through hydro-distillation, with a yield of 0.1% ( w / w ). The GC-MS analysis revealed 66 compounds, constituting 99.6% of the oil. Sesquiterpene hydrocarbons predominated (70.4%), followed by monoterpene hydrocarbons (13.2%), oxygenated sesquiterpenes (12.4%), non-terpenic compounds (2.0%), and oxygenated monoterpenes (1.6%). Major constituents included germacrene D (25.1%), ( E )-caryophyllene (17.4%), bicyclogermacrene (6.6%), α -pinene (6.2%), and β -pinene (4.7%). The assessment of antioxidant capacity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay yielded a weak effect, with an IC
50 value > 100 µg/mL. The inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells was quantified using the MTT assay, showing an IC50 value of 15.15 ± 0.68 µg/mL. Furthermore, cytotoxic effects on SK-LU-1 cell line growth were evaluated using the sulforhodamine B assay, resulting in an IC50 value of 37.45 ± 2.43 μg/mL. The anti-inflammatory activity was notable among the analyzed bioactivities of this oil. By employing a computational model, the predominant secondary metabolites in the essential oil were selected as candidates for interaction analysis with cyclooxygenase-2, an enzyme implicated in the inflammatory response. Our findings suggest that P. leptostachya leaf oil could serve as a potential source of natural compounds with prospective therapeutic effects in treating inflammatory conditions.- Published
- 2024
- Full Text
- View/download PDF
6. Advanced cellulose-based hydrogel TiO 2 catalyst composites for efficient photocatalytic degradation of organic dye methylene blue.
- Author
-
Nguyen BC, Truong TM, Nguyen NT, Dinh DN, Hollmann D, and Nguyen MN
- Abstract
Sustainable cellulose-based hydrogels are used in medicine and environmental science. Hydrogels' porosity makes them excellent adsorbents and stable substrates for immobilizing photocatalysts to remove organic dyes. Despite their potential, the implementation of hydrogels for this purpose is still limited due to their high synthesis temperature and low cellulose content. To overcome these challenges, this study develops cellulose-based hydrogels, which have a high cellulose content and can be easily synthesized under ambient conditions. Containing a higher cellulose concentration than previous hydrogels, the synthesized hydrogels are more stable and can be reused numerous times in treatment operations. The hydrogel properties were investigated using Fourier transform infrared spectroscopy, X-ray diffraction and thermal analysis. Scanning electronic microscopy revealed that TiO
2 nanoparticles were homogeneously distributed throughout the hydrogel's matrices. In addition, transparent hydrogels allow light to pass through, making them suitable substrates to remove organic dye. The results showed that the hydrogel with TiO2 was able to degrade nearly 90% of organic dye within 180 min. Furthermore, the hydrogel with the embedded catalyst exhibits the potential for reusability with a regeneration efficiency of 80.01% after five runs. These findings suggest that this novel hydrogel is a promising candidate for water pollution remediation., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
7. Conamonin A and dihydrochalcones from the whole plants of Conamomum rubidum (Lamxay & N.S.Lý) Škorničk. & A.D. Poulsen showing anti-inflammatory and cytotoxic activities.
- Author
-
Hoang HNT, Vo HQ, Nguyen LTK, Thi Tran LT, Nguyen HT, Pham TV, Le HT, Canh Le CV, Nguyen BC, and Ho DV
- Abstract
A new compound, conamonin A ( 1 ), was isolated from the whole plants of Conamomum rubidum with eight known dihydrochalcones ( 2 - 9 ). Their structures were elucidated by a combination of spectroscopic methods as well as by comparison with previously reported data. The absolute configuration of 1 was assigned by TDDFT-ECD method. Compounds 1 and 8 showed inhibitory activity against LPS-induced NO production in the RAW 264.7 cells, with IC
50 values of 58.29 ± 2.88 and 81.77 ± 5.99 μM, respectively. Compounds 3/4 and 5/6 exhibited inhibitory effects, with IC50 values of 28.76 ± 1.16 and 29.89 ± 1.79 μg/mL, respectively. Compounds 2 , 7 - 9 exhibited significant cytotoxic activity against human lung carcinoma (the SK-LU-1 cell line) with IC50 values ranging from 9.87 to 17.99 µM. This study offers valuable insights into the chemical constituents and biological activities of Conamomum rubidum , highlighting its potential as a source for discovering new anti-inflammatory and cytotoxic agents.- Published
- 2024
- Full Text
- View/download PDF
8. Rare Cause of Gastrointestinal Bleeding: A Case Report of Pancreatic Arteriovenous Malformation.
- Author
-
Nguyen TH, Tran LT, Nguyen BC, Dinh NT, Mai HT, Pham QNM, Ho LV, Ky TD, and Nguyen TL
- Subjects
- Adult, Humans, Male, Duodenum, Gastrointestinal Hemorrhage etiology, Pancreas, Pancreaticoduodenectomy, Arteriovenous Malformations complications, Arteriovenous Malformations diagnostic imaging, Chronic Pain, Duodenal Ulcer complications
- Abstract
BACKGROUND Arteriovenous malformation is an unusual cause of gastrointestinal bleeding, particularly in the pancreas. A definitive treatment strategy is not yet established. CASE REPORT We present the case of a 37-year-old man with underlying hypertension and no significant family history who presented with a 3-month history of intermittent epigastric pains and unintentional weight loss of 5 kg in 2 months. The upper endoscopy showed a large duodenal ulcer, which was uncontrolled with a standard dose of proton pump inhibitors. An abdominal computed tomography scan with contrast was indicated and revealed an enhanced mass of 2.5×3.5×4 cm in size, located on the second and third parts of the duodenum and head of the pancreas, indicating an arteriovenous malformation. On day 10 of hospitalization, the patient suddenly had melena and a drop of hemoglobin level to 5.6 g/dL; angiography intervention was successful to control the bleeding. However, gastrointestinal bleeding recurred after 2 weeks, and the patient successfully underwent a Whipple procedure. CONCLUSIONS The diagnosis and therapeutic management of arteriovenous malformations are uniquely challenging; therefore, pancreatic arteriovenous malformations should be listed on the differential diagnosis, particularly in those cases with non-healing and large duodenal ulcers. Otherwise, early imaging modalities should be performed to confirm the diagnosis. In particular, angiography can temporarily control bleeding before proceeding with more definitive therapy.
- Published
- 2023
- Full Text
- View/download PDF
9. Chemical composition and biological activities of essential oil from Grewia bulot leaves.
- Author
-
Pham TV, Ho DV, Tuan Le A, Duy Ngo Y, Thanh Thi Dang N, Quoc Le T, and Nguyen BC
- Abstract
This study focused on the chemical composition and biological activities of the essential oil derived from Grewia bulot , a plant species known for its medicinal properties. The analysis of Grewia bulot essential oil revealed the presence of 78 constituents. The major compounds were α -cadinol (13.5%), 1,8-cineole (12.7%), 1,10-di- epi -cubenol (9.8%), epi - α -cadinol (6.7%), ( E , E )- α -farnesene (5.9%), ( E )-citral (4.0%), selin-11-en-4- α -ol (4.0%), citronellol isobutanoate (3.9%), and geranic acid (3.7%). The essential oil exhibited promising antioxidant potential with an IC
50 value of 452.65 ± 28.40 µg/mL in DPPH model. This oil did not show NO production inhibitory effect in RAW 264.7 cells. In addition, the essential oil exhibited significant cytotoxicity against KB, Hep-G2, MCF-7, and SK-LU-1 cancer cell lines, with IC50 values ranging from 44.04 ± 1.47 to 74.20 ± 3.71 μg/mL.- Published
- 2023
- Full Text
- View/download PDF
10. Examining Sleep Modulation by Drosophila Ellipsoid Body Neurons.
- Author
-
Singh P, Aleman A, Omoto JJ, Nguyen BC, Kandimalla P, Hartenstein V, and Donlea JM
- Subjects
- Animals, Female, Sleep physiology, Neurons physiology, Wakefulness physiology, Drosophila melanogaster physiology, Drosophila, Drosophila Proteins genetics, Drosophila Proteins metabolism
- Abstract
Recent work in Drosophila has uncovered several neighboring classes of sleep-regulatory neurons within the central complex. However, the logic of connectivity and network motifs remains limited by the incomplete examination of relevant cell types. Using a recent genetic-anatomic classification of ellipsoid body ring neurons, we conducted a thermogenetic screen in female flies to assess sleep/wake behavior and identified two wake-promoting drivers that label ER3d neurons and two sleep-promoting drivers that express in ER3m cells. We then used intersectional genetics to refine driver expression patterns. Activation of ER3d cells shortened sleep bouts, suggesting a key role in sleep maintenance. While sleep-promoting drivers from our mini-screen label overlapping ER3m neurons, intersectional strategies cannot rule out sleep regulatory roles for additional neurons in their expression patterns. Suppressing GABA synthesis in ER3m neurons prevents postinjury sleep, and GABAergic ER3d cells are required for thermogenetically induced wakefulness. Finally, we use an activity-dependent fluorescent reporter for putative synaptic contacts to embed these neurons within the known sleep-regulatory network. ER3m and ER3d neurons may receive connections from wake-active Helicon/ExR1 cells, and ER3m neurons likely inhibit ER3d neurons. Together, these data suggest a neural mechanism by which previously uncharacterized circuit elements stabilize sleep-wake states., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Singh et al.)
- Published
- 2023
- Full Text
- View/download PDF
11. Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer.
- Author
-
Khan MM, Frustino J, Villa A, Nguyen BC, Woo SB, Johnson WE, Varelas X, Kukuruzinska M, and Monti S
- Subjects
- Humans, Transcriptome genetics, Sequence Analysis, RNA, Mouth Neoplasms genetics, Mouth Neoplasms metabolism, Mouth Neoplasms pathology, Carcinoma, Squamous Cell genetics, Precancerous Conditions genetics, Precancerous Conditions metabolism, Precancerous Conditions pathology
- Abstract
Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and the most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco- and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ~ 65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome toward PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage., (© 2023. BioMed Central Ltd., part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
12. Clinical standards for the management of adverse effects during treatment for TB.
- Author
-
Singh KP, Carvalho ACC, Centis R, D Ambrosio L, Migliori GB, Mpagama SG, Nguyen BC, Aarnoutse RE, Aleksa A, van Altena R, Bhavani PK, Bolhuis MS, Borisov S, van T Boveneind-Vrubleuskaya N, Bruchfeld J, Caminero JA, Carvalho I, Cho JG, Davies Forsman L, Dedicoat M, Dheda K, Dooley K, Furin J, García-García JM, Garcia-Prats A, Hesseling AC, Heysell SK, Hu Y, Kim HY, Manga S, Marais BJ, Margineanu I, Märtson AG, Munoz Torrico M, Nataprawira HM, Nunes E, Ong CWM, Otto-Knapp R, Palmero DJ, Peloquin CA, Rendon A, Rossato Silva D, Ruslami R, Saktiawati AMI, Santoso P, Schaaf HS, Seaworth B, Simonsson USH, Singla R, Skrahina A, Solovic I, Srivastava S, Stocker SL, Sturkenboom MGG, Svensson EM, Tadolini M, Thomas TA, Tiberi S, Trubiano J, Udwadia ZF, Verhage AR, Vu DH, Akkerman OW, Alffenaar JWC, and Denholm JT
- Subjects
- Humans, Health Personnel, Tuberculosis diagnosis, Tuberculosis drug therapy, Drug-Related Side Effects and Adverse Reactions etiology, Hypersensitivity
- Abstract
BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE. METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards. RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research. CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.
- Published
- 2023
- Full Text
- View/download PDF
13. Coronary Artery Plaque Assessment by CT Angiogram in Inflammatory Bowel Disease.
- Author
-
Ayoub M, Shah H, Nguyen BC, Mehdi M, Nagavally S, Dawson A, Al-Kindi S, Virani S, Mohananey D, Sharma A, and Sinh P
- Subjects
- Humans, Coronary Vessels, MINOCA, Angiography, Tomography, X-Ray Computed, Plaque, Atherosclerotic diagnostic imaging, Myocardial Infarction
- Published
- 2023
- Full Text
- View/download PDF
14. Vietnam Association of Gastroenterology (VNAGE) consensus on the management of Helicobacter pylori infection.
- Author
-
Quach DT, Mai BH, Tran MK, Dao LV, Tran HV, Vu KT, Vu KV, Pham HT, Bui HH, Ho DD, Trinh DT, Nguyen VT, Duong TH, Tran TT, Nguyen HT, Nguyen TT, Nguyen TD, Nguyen LC, Dao HV, Thai KD, Phan NT, Le LT, Vo CH, Ho PT, Nguyen TL, Le QD, Le NV, Phan HQ, Nguyen BC, Tran TT, Tran TV, and Ta L
- Abstract
Helicobacter pylori (H. pylori) infection is prevalent and has a rapidly increasing antibiotic resistance rate in Vietnam. Reinfection is quite common, and gastric carcinoma remains one of the most common malignancies, which is not uncommon to develop after successful eradication. The purpose of this consensus is to provide updated recommendations on the management of H. pylori infection in the country. The consensus panel consisted of 32 experts from 14 major universities and institutions in Vietnam who were invited to review the evidence and develop the statements using the Delphi method. The process followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The consensus level was defined as ≥80% for agreement on the proposed statements. Due to the limited availability of high-quality local evidence, this consensus was also based on high-quality evidence from international studies, especially those conducted in other populations in the Asia-Pacific region. The panel finally reached a consensus on 27 statements after two voting rounds, which consisted of four sections (1) indications for testing and selection of diagnostic tests (2), treatment regimens, (3) post-treatment confirmation of H. pylori status, and (4) reinfection prevention methods and follow-up after eradication. Important issues that require further evidence include studies on third-line regimens, strategies to prevent H. pylori reinfection, and post-eradication follow-up for precancerous gastric lesions. We hope this consensus will help guide the current clinical practice in Vietnam and promote multicenter studies in the country and international collaborations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Quach, Mai, Tran, Dao, Tran, Vu, Vu, Pham, Bui, Ho, Trinh, Nguyen, Duong, Tran, Nguyen, Nguyen, Nguyen, Nguyen, Dao, Thai, Phan, Le, Vo, Ho, Nguyen, Le, Le, Phan, Nguyen, Tran, Tran and Ta.)
- Published
- 2023
- Full Text
- View/download PDF
15. Antiaging Mechanism of Natural Compounds: Effects on Autophagy and Oxidative Stress.
- Author
-
Taylor E, Kim Y, Zhang K, Chau L, Nguyen BC, Rayalam S, and Wang X
- Subjects
- Autophagy, Oxidative Stress, Reactive Oxygen Species metabolism, Oleanolic Acid analogs & derivatives
- Abstract
Aging is a natural biological process that manifests as the progressive loss of function in cells, tissues, and organs. Because mechanisms that are meant to promote cellular longevity tend to decrease in effectiveness with age, it is no surprise that aging presents as a major risk factor for many diseases such as cardiovascular disease, neurodegenerative disorders, cancer, and diabetes. Oxidative stress, an imbalance between the intracellular antioxidant and overproduction of reactive oxygen species, is known to promote the aging process. Autophagy, a major pathway for protein turnover, is considered as one of the hallmarks of aging. Given the progressive physiologic degeneration and increased risk for disease that accompanies aging, many studies have attempted to discover new compounds that may aid in the reversal of the aging process. Here, we summarize the antiaging mechanism of natural or naturally derived synthetic compounds involving oxidative stress and autophagy. These compounds include: 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) derivatives (synthetic triterpenoids derived from naturally occurring oleanolic acid), caffeic acid phenethyl ester (CAPE, the active ingredient in honey bee propolis), xanthohumol (a prenylated flavonoid identified in the hops plant), guggulsterone (a plant steroid found in the resin of the guggul plant), resveratrol (a natural phenol abundantly found in grape), and sulforaphane (a sulfur-containing compound found in cruciferous vegetables).
- Published
- 2022
- Full Text
- View/download PDF
16. Chemical constituents from the Knema globularia fruits and their in vitro cytotoxicity.
- Author
-
Pham TV, Bach HKT, Ho DV, and Nguyen BC
- Subjects
- Cell Line, Tumor, Fruit, Molecular Structure, Antineoplastic Agents, Phytogenic pharmacology, Myristicaceae, Plantaginaceae
- Abstract
Two new compounds, designated as knecorticosanones A-B ( 1 - 2 ), along with three known compounds ( 3 - 5 ) were isolated from the fruits of Knema globularia . Their structures were elucidated by extensive spectroscopy analysis, including 1D- and 2D-NMR, UV, IR, and HRESIMS and by comparison with the reported data in the literature. Compounds 1 - 5 were evaluated for their cytotoxicity. Knecorticosanone B ( 2 ) and malabaricone D ( 5 ) exhibited moderate cytotoxic effect against Hep-G2, MCF-7 and SK-LU-1 cell lines with IC
50 values ranging from 8.76 ± 1.02 to 18.74 ± 1.75 μM while knecorticosanone A ( 1 ), virolane ( 3 ) and 7-hydroxy-3',4'-methylenedioxyflavan ( 4 ) exhibited weak inhibitory effect against these cell lines with IC50 values ranging from 25.85 ± 2.75 to 66.75 ± 2.08 μM.- Published
- 2022
- Full Text
- View/download PDF
17. Ouabain inhibitor rostafuroxin attenuates dextromethorphan-induced manic potential.
- Author
-
Shin EJ, Nguyen BT, Jeong JH, Hoai Nguyen BC, Tran NKC, Sharma N, Kim DJ, Nah SY, Lichtstein D, Nabeshima T, and Kim HC
- Subjects
- Animals, Disease Models, Animal, Locomotion drug effects, Male, Mice, Signal Transduction drug effects, Androstanols pharmacology, Bipolar Disorder chemically induced, Bipolar Disorder metabolism, Dextromethorphan adverse effects, Ouabain antagonists & inhibitors
- Abstract
Dextromethorphan (DM) abuse produces mania-like symptoms in humans. ERK/Akt signaling activation involved in manic potential can be attenuated by the inhibition of ouabain-like cardiac steroids. In this study, increased phosphorylations of ERK/Akt and hyperlocomotion induced by DM (30 mg/kg, i.p./day × 7) were significantly protected by the ouabain inhibitor rostafuroxin (ROSTA), suggesting that DM induces the manic potential. ROSTA significantly attenuated DM-induced protein kinase C δ (PKCδ) phosphorylation, GluN2B (i.e., MDA receptor subunit) expression, and phospho-PKCδ/GluN2B interaction. DM instantly upregulated the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent system. However, DM reduced Nrf2 nuclear translocation, Nrf2 DNA binding activity, γ-glutamylcysteine mRNA expression, and subsequent GSH/GSSG level and enhanced oxidative parameters following 1-h of administration. ROSTA, PKCδ inhibitor rottlerin, and GluN2B inhibitor traxoprodil significantly attenuated DM-induced alterations in Nrf2-related redox parameters and locomotor activity induced by DM in wild-type mice. Importantly, in PKCδ knockout mice, DM failed to alter the above parameters. Further, ROSTA and traxoprodil also failed to enhance PKCδ depletion effect, suggesting that PKCδ is a critical target for the anti-manic potential of ROSTA or GluN2B antagonism. Our results suggest that ROSTA inhibits DM-induced manic potential by attenuating ERK/Akt activation, GluN2B/PKCδ signalings, and Nrf2-dependent system., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
18. Impacts of Residual Self-Interference, Hardware Impairment and Cascade Rayleigh Fading on the Performance of Full-Duplex Vehicle-to-Vehicle Relay Systems.
- Author
-
Nguyen BC, The Dung L, Nguyen HM, Kim T, and Kim YI
- Subjects
- Computer Simulation, Monte Carlo Method, Probability, Computer Communication Networks, Computers
- Abstract
In practice, self-interference (SI) in full-duplex (FD) wireless communication systems cannot be completely eliminated due to imperfections in different factors, such as the SI channel estimation and hardware circuits. Therefore, residual SI (RSI) always exists in FD systems. In addition, hardware impairments (HIs) cannot be avoided in FD systems due to the non-ideal characteristics of electronic components. These issues motivate us to consider an FD-HI system with a decode-and-forward (DF) relay that is applied for vehicle-to-vehicle (V2V) communication. Unlike previous works, the performance of the proposed FD-HI-V2V system is evaluated over cascaded Rayleigh fading channels (CRFCs). We mathematically obtain the exact closed-form expressions of the outage probability (OP), system throughput (ST), and ergodic capacity (EC) of the proposed FD-HI-V2V system under the joint and crossed effects of the RSI, HIs, and CRFCs. We validate all derived expressions via Monte-Carlo simulations. Based on these expressions, the OP, ST, and EC of the proposed FD-HI-V2V system are investigated and compared with other related systems, such as ideal hardware (ID) and half-duplex (HD) systems, as well as a system over traditional Rayleigh fading channels (RFCs), to clearly show the impacts of negative factors.
- Published
- 2021
- Full Text
- View/download PDF
19. Outage and throughput analysis of power-beacon assisted nonlinear energy harvesting NOMA multi-user relay system over Nakagami- m fading channels.
- Author
-
Manh Hoang T, Nguyen BC, Trung TT, and Dung LT
- Abstract
This paper considers a non-orthogonal multiple access (NOMA) multi-user relay system where both source and relay harvest the energy from a power beacon (PB) equipped with multiple antennas and use this harvested energy to transmit signals to several users. Realistic nonlinear energy harvesting models are applied, and time switching protocols are adopted at source and relay. We successfully derive the exact closed-form expressions of the outage probability and throughput of the system over Nakagami- m fading channels. Then, we use Monte-Carlo simulations to validate the correctness of these derived mathematical expressions. Numerical results show that a higher saturated power threshold of the nonlinear energy harvester results in lower outage probability and higher throughput. Moreover, the optimal time switching ratio that maximizes the throughput is smaller than the optimal time switching ratio that minimizes the outage probability., Competing Interests: The authors declare no conflict of interest., (© 2020 Published by Elsevier Ltd.)
- Published
- 2020
- Full Text
- View/download PDF
20. β-Catenin/CBP inhibition alters epidermal growth factor receptor fucosylation status in oral squamous cell carcinoma.
- Author
-
Chandler KB, Alamoud KA, Stahl VL, Nguyen BC, Kartha VK, Bais MV, Nomoto K, Owa T, Monti S, Kukuruzinska MA, and Costello CE
- Subjects
- Animals, Binding Sites, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Bridged Bicyclo Compounds, Heterocyclic pharmacology, CREB-Binding Protein metabolism, Carcinoma, Squamous Cell metabolism, Cell Line, Tumor, ErbB Receptors chemistry, ErbB Receptors metabolism, Fucosyltransferases metabolism, Gene Expression Regulation, Neoplastic drug effects, Humans, Mice, Models, Molecular, Mouth Neoplasms genetics, Mouth Neoplasms metabolism, Neoplasm Metastasis, Polysaccharides metabolism, Protein Structure, Tertiary, Pyrimidinones administration & dosage, Pyrimidinones pharmacology, Small Molecule Libraries pharmacology, Wnt Signaling Pathway drug effects, Xenograft Model Antitumor Assays, beta Catenin metabolism, Galactoside 2-alpha-L-fucosyltransferase, Carcinoma, Squamous Cell drug therapy, Fucose metabolism, Fucosyltransferases genetics, Mouth Neoplasms drug therapy, Small Molecule Libraries administration & dosage
- Abstract
Epidermal growth factor receptor (EGFR) is a major driver of head and neck cancer, a devastating malignancy with a major sub-site in the oral cavity manifesting as oral squamous cell carcinoma (OSCC). EGFR is a glycoprotein receptor tyrosine kinase (RTK) whose activity is upregulated in >80% OSCC. Current anti-EGFR therapy relies on the use of cetuximab, a monoclonal antibody against EGFR, although it has had only a limited response in patients. Here, we uncover a novel mechanism regulating EGFR activity, identifying a role of the nuclear branch of the Wnt/β-catenin signaling pathway, the β-catenin/CBP axis, in control of post-translational modification of N-glycans on the EGFR. Genomic and structural analyses reveal that β-catenin/CBP signaling represses fucosylation on the antennae of N-linked glycans on EGFR. By employing nUPLC-MS/MS, we determined that malignant human OSCC cells harbor EGFR with a paucity of N-glycan antennary fucosylation, while indolent cells display higher levels of fucosylation at sites N420 and N579. Additionally, treatment with either ICG-001 or E7386, which are both small molecule inhibitors of β-catenin/CBP signaling, leads to increased transcriptional expression of fucosyltransferases FUT2 and FUT3, with a concomitant increase in EGFR N-glycan antennary fucosylation. In order to discover which fucosylated glycan epitopes are involved in the observed effect, we performed in-depth characterization of multiply-fucosylated N-glycans via tandem mass spectrometry analysis of the EGFR tryptic glycopeptides. Data are available via ProteomeXchange with identifier PXD017060. We propose that β-catenin/CBP signaling promotes EGFR oncogenic activity in OSCC by inhibiting its N-glycan antennary fucosylation through transcriptional repression of FUT2 and FUT3.
- Published
- 2020
- Full Text
- View/download PDF
21. Impacts of Imperfect Channel State Information, Transceiver Hardware, and Self-Interference Cancellation on the Performance of Full-Duplex MIMO Relay System.
- Author
-
Nguyen BC, Thang NN, Tran XN, and Dung LT
- Abstract
Imperfect channel state information (I-CSI) and imperfect transceiver hardware often happen in wireless communication systems due to the time-varying and random characteristics of both wireless channels and hardware components. The impacts of I-CSI and hardware impairments (HI) reduce not only the system performance but also the self-interference cancellation (SIC) capability of full-duplex (FD) devices. To investigate the system performance in realistic scenarios, in this paper, we consider the performance of an FD multiple-input multiple-output (MIMO) relay system under the effects of I-CSI, imperfect SIC (I-SIC), and imperfect transceiver hardware. We mathematically derive the exact closed-form expressions of the outage probability (OP) and ergodic capacity of the considered HI-FD-MIMO relay system over Rayleigh fading channels with the existence of I-CSI, I-SIC, and HI. Numerical results indicate that the performance in terms of OP and capacity reaches saturation faster, especially when the channel estimation error, the residual self-interference (RSI), and HI levels are remarkable. Therefore, various solutions for effectively reducing the channel estimation error, RSI, and HI levels in the HI-FD-MIMO relay system should be carried out to improve the system performance. All derived mathematical expressions are verified through Monte-Carlo simulations.
- Published
- 2020
- Full Text
- View/download PDF
22. Closed-Form Expression for the Symbol Error Probability in Full-Duplex Spatial Modulation Relay System and Its Application in Optimal Power Allocation.
- Author
-
Nguyen LV, Nguyen BC, Tran XN, and Dung LT
- Abstract
Full-duplex (FD) communication and spatial modulation (SM) are two promising techniques to achieve high spectral efficiency. Recent works in the literature have investigated the possibility of combining the FD mode with SM in the relay system to benefit their advantages. In this paper, we analyze the performance of the FD-SM decode-and-forward (DF) relay system and derive the closed-form expression for the symbol error probability (SEP). To tackle the residual self-interference (RSI) due to the FD mode at the relay, we propose a simple yet effective power allocation algorithm to compensate for the RSI impact and improve the system SEP performance. Both numerical and simulation results confirm the accuracy of the derived SEP expression and the efficacy of the proposed optimal power allocation.
- Published
- 2019
- Full Text
- View/download PDF
23. On the Performance of Energy Harvesting Non-Orthogonal Multiple Access Relaying System with Imperfect Channel State Information over Rayleigh Fading Channels.
- Author
-
Hoang TM, Van NL, Nguyen BC, and Dung LT
- Abstract
In this paper, we propose a non-orthogonal multiple access (NOMA) relaying system, where a source node communicates simultaneously with multiple users via the assistance of the best amplify-and-forward (AF) relay. The best relay is selected among N relays which are capable of harvesting the energy from radio frequency (RF) signals. We analyze the performance of the proposed NOMA relaying system in the conditions of imperfect channel state information (CSI) and Rayleigh fading by deriving the exact expressions of the outage probability (OP) and the approximate expression of the ergodic capacities of each user and the whole system. We also determine the optimal energy harvesting duration which minimizes the OP. Numerical results show that, for the same parameter settings, the performance of the proposed NOMA relaying system, especially the ergodic capacity of the whole system, outperforms that of the orthogonal-multiple-access (OMA) relaying system. Monte-Carlo simulations are used to validate the correctness of the analytical results.
- Published
- 2019
- Full Text
- View/download PDF
24. Understanding Risk Behaviors of Vietnamese Adults with Chronic Hepatitis B in an Urban Setting.
- Author
-
Le TV, Vu TTM, Dang AK, Vu GT, Nguyen LH, Nguyen BC, Tran TH, Tran BX, Latkin CA, Ho CSH, and Ho RCM
- Subjects
- Adult, Condoms, Cross-Sectional Studies, Female, Hepatitis B, Chronic epidemiology, Humans, Logistic Models, Male, Middle Aged, Risk Factors, Sexual Behavior, Sexual Partners, Urban Population statistics & numerical data, Vietnam epidemiology, Alcohol Drinking epidemiology, Hepatitis B, Chronic psychology, Risk-Taking, Smoking epidemiology, Unsafe Sex statistics & numerical data
- Abstract
Cigarette smoking and alcohol consumption can be considered as risk factors that increase the progression of chronic liver disease. Meanwhile, unprotected sex is one of the main causes of hepatitis B infection. This study aimed to explore drinking, smoking, and risky sexual behaviors among people with chronic hepatitis B virus (HBV) in a Vietnamese urban setting, as well as investigating potential associated factors. A cross-sectional study was performed in October 2018 in Viet-Tiep Hospital, Hai Phong, Vietnam. A total of 298 patients who had been diagnosed with chronic hepatitis B reported their smoking status, alcohol use, and sexual risk behavior in the last 12 months. A multivariate logistic regression model was used to identify the associated factors. It was identified that 82.5% of participants never used alcohol. The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive result among male patients was 7.4% (0% in female patients). In addition, 14.5% of participants were current smokers and the mean number of cigarettes per day was 7.4 (SD = 3.4). It was found that 35.4% of male patients had sex with two or more sex partners. Furthermore, 66.7% and 74.1% of participants used condoms when having sex with casual partners/one-night stands and sex workers, respectively. There was a positive correlation between monthly drinking and currently smoking. White-collar workers were less likely to have multiple sex partners within the last 12 months. Our study highlights the need for integrating counseling sessions and educational programs with treatment services.
- Published
- 2019
- Full Text
- View/download PDF
25. Social Determinants of Stigma and Discrimination in Vietnamese Patients with Chronic Hepatitis B.
- Author
-
Le TV, Vu TTM, Mai HT, Nguyen LH, Truong NT, Hoang CL, Nguyen SH, Nguyen CT, Nguyen BC, Tran TH, Tran BX, Latkin CA, Ho CSH, and Ho RCM
- Subjects
- Adult, Cross-Sectional Studies, Female, Hepatitis B, Chronic epidemiology, Humans, Male, Risk Factors, Vietnam epidemiology, Hepatitis B, Chronic psychology, Social Discrimination statistics & numerical data, Social Stigma
- Abstract
Vietnam is among the countries with the highest prevalence of chronic hepatitis B (CHB) and individuals who suffer from CHB oftentimes perceive high levels of stigma and discrimination. Our study aimed to provide evidence on the prevalence of stigma against hepatitis B virus (HBV), HBV infection, and social determinants of stigma and discrimination in patients. A cross-sectional study was conducted at Viet-Tiep Hospital, Hai Phong, Vietnam. Stigma and discrimination against CHB in the last month were measured via four dimensions: (1) Blame/Judgment; (2) Shame; (3) Discrimination in different settings; (4) Disclosure of CHB status. Multivariate Logistic and Tobit regressions were used to identify factors associated with CHB-related stigma and discrimination. Among 298 enrolled patients, 4.8% experienced blame/judgement, 10.2% perceived shame, 48.5% felt discriminated in healthcare facilities, and 90.6% disclosed their health status with spouses/partners. Factors associated with lower odds of CHB-related stigma/discrimination included living with spouses/partners, old age, being employed, and the existence of comorbidities was linked with higher odds of stigma. Anti-stigma programs should target those who are younger and have comorbidities. This could be done by community-based interventions which focus on inaccurate beliefs about viral hepatitis. Furthermore, families, healthcare providers, and society should play a crucial role in supporting CHB patients.
- Published
- 2019
- Full Text
- View/download PDF
26. Socioeconomic Vulnerability to Depressive Symptoms in Patients with Chronic Hepatitis B.
- Author
-
Vu TTM, Le TV, Dang AK, Nguyen LH, Nguyen BC, Tran BX, Latkin CA, Ho CSH, and Ho RCM
- Subjects
- Adult, Aged, Cross-Sectional Studies, Depression psychology, Female, Humans, Male, Middle Aged, Prevalence, Quality of Life psychology, Social Class, Vietnam epidemiology, Young Adult, Depression epidemiology, Hepatitis B, Chronic virology, Socioeconomic Factors
- Abstract
Depression is considered one of the most prevalent psychiatric disorders among patients with hepatitis B virus (HBV)-related liver disease and has adverse effects on the disease progression. However, there is a scarcity of studies contributing to the assessement of depression in hepatitis B patients. There is also little research into risk factors, particularly underlying socio-economic factors in Vietnam where the prevalence of hepatitis B is high. This study aimed to examine depression and identify whether differences in socio-economic status is related to the level of depression amongst chronic hepatitis B patients. A cross-sectional study was conducted on 298 patients with chronic hepatitis B at The Chronic Hepatitis Clinic in the Viet-Tiep Hospital, Hai Phong, Vietnam. The Patient Health Questionnaire-9 (PHQ-9) and EuroQol-5 dimensions-5 levels (EQ-5D-5L) were used to assess the severity of depression and health-related quality of life (HRQOL). Of chronic hepatitis B patients, 37.5% experienced depressive symptoms and most of them suffered minimal depressive symptoms (31.4%). According to the result of the multivariate logistic regression model, we found that higher age, lower income level, unemployement, living with spouse/partners were positively associated with having depression. Furthermore, having physical health problems and lower health-related quality of life were also related to a higher risk of depression. We recommend family support, financial support and active participation in consultation should be conducted during treatment to improve the quality of life and the emotional state of HBV patients.
- Published
- 2019
- Full Text
- View/download PDF
27. 5-HT 1A receptor agonist 8-OH-DPAT induces serotonergic behaviors in mice via interaction between PKCδ and p47phox.
- Author
-
Tran HQ, Shin EJ, Hoai Nguyen BC, Phan DH, Kang MJ, Jang CG, Jeong JH, Nah SY, Mouri A, Saito K, Nabeshima T, and Kim HC
- Subjects
- 8-Hydroxy-2-(di-n-propylamino)tetralin, Animals, Behavior, Animal drug effects, Hypothalamus drug effects, Hypothalamus metabolism, Male, Mice, Mice, Inbred C57BL, NADPH Oxidases genetics, Phosphorylation drug effects, Protein Binding, Protein Kinase C-delta genetics, Receptor, Serotonin, 5-HT1A genetics, Serotonin Syndrome genetics, Serotonin Syndrome metabolism, Serotonin Syndrome psychology, NADPH Oxidases metabolism, Protein Kinase C-delta metabolism, Receptor, Serotonin, 5-HT1A metabolism, Serotonin metabolism, Serotonin 5-HT1 Receptor Agonists administration & dosage, Serotonin Syndrome drug therapy
- Abstract
Serotonin syndrome is an adverse reaction due to increased serotonin (5-hydroxytryptophan: 5-HT) concentrations in the central nervous system (CNS). The full 5-HT
1A receptor (5-HT1A R) agonist (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) has been recognized to elicit traditional serotonergic behaviors. Treatment with 8-OH-DPAT selectively increased PKCδ expression out of PKC isoforms and 5-HT turnover rate in the hypothalamus of wild-type mice. Treatment with 8-OH-DPAT resulted in oxidative burdens, co-immunoprecipitation of 5-HT1A R and PKCδ, and phosphorylation and membrane translocation of p47phox. Importantly, p47phox also interacted with 5-HT1A R or PKCδ in the presence of 8-OH-DPAT. Consistently, the interaction and oxidative burdens were attenuated by 5-HT1A R antagonism (i.e., WAY100635), PKCδ inhibition (i.e., rottlerin and genetic depletion of PKCδ), or NADPH oxidase/p47phox inhibition (i.e., apocynin and genetic depletion of p47phox). However, WAY100635, apocynin, or rottlerin did not exhibit any additive effects against the protective effect by inhibition of PKCδ or p47phox. Furthermore, apocynin, rottlerin, or WAY100635 also significantly protected from pro-inflammatory/pro-apoptotic changes induced by 8-OH-DPAT. Therefore, we suggest that 8-OH-DPAT-induced serotonergic behaviors requires oxidative stress, pro-inflammatory, and pro-apoptotic changes, that PKCδ or p47phox mediates the serotonergic behaviors induced by 8-OH-DPAT, and that the inhibition of PKCδ-dependent p47phox activation is critical for protecting against serotonergic behaviors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
28. Functional and genomic analyses reveal therapeutic potential of targeting β-catenin/CBP activity in head and neck cancer.
- Author
-
Kartha VK, Alamoud KA, Sadykov K, Nguyen BC, Laroche F, Feng H, Lee J, Pai SI, Varelas X, Egloff AM, Snyder-Cappione JE, Belkina AC, Bais MV, Monti S, and Kukuruzinska MA
- Subjects
- Animals, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Cell Adhesion genetics, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival genetics, Disease Progression, Epithelial Cells drug effects, Epithelial Cells pathology, Gene Expression Profiling, Gene Expression Regulation, Neoplastic drug effects, Head and Neck Neoplasms pathology, Humans, Mice, Inbred C57BL, Mice, Nude, Mouth Neoplasms drug therapy, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Phenotype, Pyrimidinones pharmacology, Pyrimidinones therapeutic use, Survival Analysis, Wnt Signaling Pathway genetics, Zebrafish embryology, Genomics, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms genetics, Molecular Targeted Therapy, Peptide Fragments metabolism, Sialoglycoproteins metabolism, beta Catenin metabolism
- Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy characterized by tumor heterogeneity, locoregional metastases, and resistance to existing treatments. Although a number of genomic and molecular alterations associated with HNSCC have been identified, they have had limited impact on the clinical management of this disease. To date, few targeted therapies are available for HNSCC, and only a small fraction of patients have benefited from these treatments. A frequent feature of HNSCC is the inappropriate activation of β-catenin that has been implicated in cell survival and in the maintenance and expansion of stem cell-like populations, thought to be the underlying cause of tumor recurrence and resistance to treatment. However, the therapeutic value of targeting β-catenin activity in HNSCC has not been explored., Methods: We utilized a combination of computational and experimental profiling approaches to examine the effects of blocking the interaction between β-catenin and cAMP-responsive element binding (CREB)-binding protein (CBP) using the small molecule inhibitor ICG-001. We generated and annotated in vitro treatment gene expression signatures of HNSCC cells, derived from human oral squamous cell carcinomas (OSCCs), using microarrays. We validated the anti-tumorigenic activity of ICG-001 in vivo using SCC-derived tumor xenografts in murine models, as well as embryonic zebrafish-based screens of sorted stem cell-like subpopulations. Additionally, ICG-001-inhibition signatures were overlaid with RNA-sequencing data from The Cancer Genome Atlas (TCGA) for human OSCCs to evaluate its association with tumor progression and prognosis., Results: ICG-001 inhibited HNSCC cell proliferation and tumor growth in cellular and murine models, respectively, while promoting intercellular adhesion and loss of invasive phenotypes. Furthermore, ICG-001 preferentially targeted the ability of subpopulations of stem-like cells to establish metastatic tumors in zebrafish. Significantly, interrogation of the ICG-001 inhibition-associated gene expression signature in the TCGA OSCC human cohort indicated that the targeted β-catenin/CBP transcriptional activity tracked with tumor status, advanced tumor grade, and poor overall patient survival., Conclusions: Collectively, our results identify β-catenin/CBP interaction as a novel target for anti-HNSCC therapy and provide evidence that derivatives of ICG-001 with enhanced inhibitory activity may serve as an effective strategy to interfere with aggressive features of HNSCC.
- Published
- 2018
- Full Text
- View/download PDF
29. 1,2,3-Triazolyl ester of ketorolac (15K): Boosting both heat-endurance and lifespan of C. elegans by down-regulating PAK1 at nM levels.
- Author
-
Nguyen BC, Kim SA, Won SM, Park SK, Uto Y, and Maruta H
- Subjects
- Animals, Caenorhabditis elegans drug effects, Caenorhabditis elegans metabolism, Caenorhabditis elegans Proteins metabolism, Gene Expression Regulation, Enzymologic drug effects, Hot Temperature, Ketorolac analogs & derivatives, Longevity drug effects, Molecular Structure, Triazoles chemistry, Caenorhabditis elegans growth & development, Down-Regulation, Triazoles pharmacology, p21-Activated Kinases metabolism
- Abstract
PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic/ageing kinase, and its dysfunction extends the healthy lifespan of C. elegans by activating HSP16 gene. 15K is a highly cell-permeable 1,2,3-triazolyl ester of ketorolac that down-regulates both PAK1 and its down-stream COX-2 in R- and S-forms, respectively. 15K is 500-5,000 times more potent than ketorolac, an old pain-killer, inhibiting the growth of cancer cell lines with IC50 ranging 5-24 nM. Scores of natural and synthetic PAK1-blockers have been shown to extend the lifespan of small animals such as C. elegans, but none of them has been effective at nM levels. Thus, we examined in vivo effect of 15K at nM levels on the survival rate of C. elegans with or without heat-shock. Like the PAK1-deficient mutant, 15K (at 50 nM)-treated worm significantly lives longer, is far more heat-resistant and less productive (fertile) than the non-treated counterpart, with an increased expression of HSP16 gene. 15K has been proven to be among the most potent anti-cancerous and longevity-promoting PAK1-blockers, and therefore has a potential to treat a variety of solid tumours without severe side effect.
- Published
- 2018
- Full Text
- View/download PDF
30. Freehand Versus Guided Surgery: Factors Influencing Accuracy of Dental Implant Placement.
- Author
-
Choi W, Nguyen BC, Doan A, Girod S, Gaudilliere B, and Gaudilliere D
- Subjects
- Humans, Imaging, Three-Dimensional, Software, Clinical Competence, Cone-Beam Computed Tomography, Dental Implantation, Endosseous methods, Dental Implants, Jaw, Edentulous, Partially rehabilitation, Outcome and Process Assessment, Health Care, Surgery, Computer-Assisted methods
- Abstract
Introduction: Patient anatomy, practitioner experience, and surgical approach are all factors that influence implant accuracy. However, the relative importance of each factor is poorly understood. The present study aimed to identify which factors most critically determine implant accuracy to aid the practitioner in case selection for guided versus freehand surgery., Methods: One practitioner's ideal implant angulation and position was compared with his achieved position radiographically for 450 implants placed using a conventional freehand method. The relative contribution of 11 demographic, anatomical, and surgical factors to the accuracy of implant placement was systematically quantified., Discussion: The most important predictors of angulation and position accuracy were the number of adjacent implants placed and the tooth-borne status of the site. Immediate placement also significantly increased position accuracy, whereas cases with narrow sites were significantly more accurate in angulation. Accuracy also improved with the practitioner's experience., Conclusion: These results suggest tooth-borne, single-implant cases performed later in the practitioner's experience are most appropriate for freehand placement, whereas guided surgery should be considered to improve accuracy for multiple-implant cases in edentulous or partially edentulous sites.
- Published
- 2017
- Full Text
- View/download PDF
31. The serum/PDGF-dependent "melanogenic" role of the minute level of the oncogenic kinase PAK1 in melanoma cells proven by the highly sensitive kinase assay.
- Author
-
Be Tu PT, Nguyen BC, Tawata S, Yun CY, Kim EG, and Maruta H
- Subjects
- Animals, Cell Line, Tumor, Down-Regulation, Gene Expression Regulation, Neoplastic, Melanins metabolism, Melanoma, Experimental blood, Melanoma, Experimental genetics, Mice, Models, Biological, RNA Interference, p21-Activated Kinases metabolism, 1-Methyl-3-isobutylxanthine pharmacology, Melanocyte-Stimulating Hormones pharmacology, Melanoma, Experimental metabolism, Platelet-Derived Growth Factor metabolism, p21-Activated Kinases genetics
- Abstract
We previously demonstrated that the oncogenic kinase PAK4, which both melanomas and normal melanocytes express at a very high level, is essential for their melanogenesis. In the present study, using the highly sensitive "Macaroni-Western" (IP-ATP-Glo) kinase assay, we investigated the melanogenic potential of another oncogenic kinase PAK1, which melanoma (B16F10) cells express only at a very minute level. After transfecting melanoma cells with PAK1-shRNA for silencing PAK1 gene, melanin content, tyrosinase activity, and kinase activity of PAK1 were compared between the wild-type and transfectants. We found that (i) PAK1 is significantly activated by melanogenic hormones such as IBMX (3-isobutyl-1-methyl xanthine) and α-MSH (melanocyte-stimulating hormone), (ii) silencing the endogenous PAK1 gene in melanoma cells through PAK1-specific shRNA reduces both melanin content and tyrosinase activity in the presence of both serum and melanogenic hormones to the basal level, (iii) the exogenously added wild-type PAK1 in the melanoma cells boosts the α-MSH-inducible melanin level by several folds without affecting the basal, and (iv) α-MSH/IBMX-induced melanogenesis hardly takes place in the absence of either serum or PAK1, clearly indicating that PAK1 is essential mainly for serum- and α-MSH/IBMX-dependent melanogenesis, but not the basal, in melanoma cells. The outcome of this study might provide the first scientific basis for explaining why a wide variety of herbal PAK1-blockers such as CAPE (caffeic acid phenethyl ester), curcumin and shikonin in cosmetics are useful for skin-whitening.
- Published
- 2017
- Full Text
- View/download PDF
32. Hair Growth Promoting and Anticancer Effects of p21-activated kinase 1 (PAK1) Inhibitors Isolated from Different Parts of Alpinia zerumbet.
- Author
-
Taira N, Nguyen BC, and Tawata S
- Subjects
- Antineoplastic Agents chemistry, Antineoplastic Agents isolation & purification, Cell Line, Cell Proliferation drug effects, Cell Survival drug effects, Diterpenes chemistry, Diterpenes isolation & purification, Epithelial Cells cytology, Epithelial Cells enzymology, Flowers chemistry, Furans chemistry, Furans isolation & purification, Furans pharmacology, Gene Expression, Glucuronides chemistry, Glucuronides isolation & purification, Hair Follicle cytology, Hair Follicle drug effects, Hair Follicle enzymology, Humans, Kaempferols chemistry, Kaempferols isolation & purification, Minoxidil pharmacology, Plant Leaves chemistry, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors isolation & purification, Quinolizines chemistry, Quinolizines isolation & purification, Quinolizines pharmacology, Rhizome chemistry, p21-Activated Kinases antagonists & inhibitors, p21-Activated Kinases metabolism, Alpinia chemistry, Antineoplastic Agents pharmacology, Diterpenes pharmacology, Epithelial Cells drug effects, Glucuronides pharmacology, Kaempferols pharmacology, Protein Kinase Inhibitors pharmacology, p21-Activated Kinases genetics
- Abstract
PAK1 (p21-activated kinase 1) is an emerging target for the treatment of hair loss (alopecia) and cancer; therefore, the search for PAK1 blockers to treat these PAK1-dependent disorders has received much attention. In this study, we evaluated the anti-alopecia and anticancer effects of PAK1 inhibitors isolated from Alpinia zerumbet (alpinia) in cell culture. The bioactive compounds isolated from alpinia were found to markedly promote hair cell growth. Kaempferol-3- O -β-d-glucuronide (KOG) and labdadiene, two of the isolated compounds, increased the proliferation of human follicle dermal papilla cells by approximately 117%-180% and 132%-226%, respectively, at 10-100 μM. MTD (2,5-bis(1 E ,3 E ,5 E )-6-methoxyhexa-1,3,5-trien-1-yl)-2,5-dihydrofuran) and TMOQ (( E )-2,2,3,3-tetramethyl-8-methylene-7-(oct-6-en-1-yl)octahydro-1 H -quinolizine) showed growth-promoting activity around 164% and 139% at 10 μM, respectively. The hair cell proliferation induced by these compounds was significantly higher than that of minoxidil, a commercially available treatment for hair loss. Furthermore, the isolated compounds from alpinia exhibited anticancer activity against A549 lung cancer cells with IC
50 in the range of 67-99 μM. Regarding the mechanism underlying their action, we hypothesized that the anti-alopecia and anticancer activities of these compounds could be attributed to the inhibition of the oncogenic/aging kinase PAK1.- Published
- 2017
- Full Text
- View/download PDF
33. The Chemistry and Biological Activities of Mimosine: A Review.
- Author
-
Nguyen BC and Tawata S
- Subjects
- Humans, Mimosine chemistry
- Abstract
Mimosine [β-[N-(3-hydroxy-4-oxypyridyl)]-α-aminopropionic acid] is a non-protein amino acid found in the members of Mimosoideae family. There are a considerable number of reports available on the chemistry, methods for estimation, biosynthesis, regulation, and degradation of this secondary metabolite. On the other hand, over the past years of active research, mimosine has been found to have various biological activities such as anti-cancer, antiinflammation, anti-fibrosis, anti-influenza, anti-virus, herbicidal and insecticidal activities, and others. Mimosine is a leading compound of interest for use in the development of RAC/CDC42-activated kinase 1 (PAK1)-specific inhibitors for the treatment of various diseases/disorders, because PAK1 is not essential for the growth of normal cells. Interestingly, the new roles of mimosine in malignant glioma treatment, regenerative dentistry, and phytoremediation are being emerged. These identified properties indicate an exciting future for this amino acid. The present review is focused on the chemistry and recognized biological activities of mimosine in an attempt to draw a link between these two characteristics. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
34. Do Socioeconomic Factors and Race Determine the Likelihood of Breast-Conserving Surgery?
- Author
-
Nguyen BC, Alawadi ZM, Roife D, Kao LS, Ko TC, and Wray CJ
- Subjects
- Aged, Early Detection of Cancer economics, Female, Humans, Logistic Models, Middle Aged, Retrospective Studies, Texas, Breast Neoplasms surgery, Ethnicity statistics & numerical data, Healthcare Disparities economics, Healthcare Disparities ethnology, Mastectomy, Segmental statistics & numerical data, Socioeconomic Factors
- Abstract
Background: Racial disparities in the use of breast-conserving surgery (BCS) have been reported and may be due to advanced stage at diagnosis. Our hypothesis was that low-income and ethnic minority patients have an increased tumor size at diagnosis and decreased likelihood of BCS., Patients and Methods: A retrospective review was conducted of early stage breast cancer patients from 10 hospitals in Harris County, Texas, between 2004 and 2011. Clinical stage was calculated on the basis of data from the institutional tumor registries and electronic medical records. Zip code-based socioeconomic factors were downloaded from the US Census Bureau (http://www.census.gov/). Linear regression was used to identify predictors of tumor size, and logistic regression was used to identify predictors of BCS., Results: The cohort included 3937 patients, comprising 2546 (65%) whites, 535 (14%) African Americans, 482 (11%) Hispanics, and 374 (10%) Asian/others. Multivariate linear regression demonstrated socioeconomic status (SES), younger age, African American, Hispanic race, and hormone receptor-negative tumors to be associated with increased tumor size at diagnosis (P < .05). Hispanic and Asian/other race, larger tumor size, combined estrogen receptor-negative/progesterone receptor-negative tumors were associated with not receiving BCS., Conclusion: Race and SES were both associated with larger tumor size at diagnosis. Larger tumor size, negative hormone receptor status, and Hispanic and Asian race were associated with lack of receipt of BCS. Breast cancer screening programs should target both minority and low SES groups. Rates of BCS should be interpreted cautiously when used as a quality metric because of the multiple factors, including tumor size and biology, contributing to its use., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
35. Effect of Okinawa Propolis on PAK1 Activity, Caenorhabditis elegans Longevity, Melanogenesis, and Growth of Cancer Cells.
- Author
-
Taira N, Nguyen BC, Be Tu PT, and Tawata S
- Subjects
- Animals, Caenorhabditis elegans growth & development, Humans, Japan, Neoplasms enzymology, p21-Activated Kinases metabolism, Caenorhabditis elegans drug effects, Cell Proliferation drug effects, Longevity drug effects, Melanins metabolism, Neoplasms physiopathology, Propolis chemistry, p21-Activated Kinases antagonists & inhibitors
- Abstract
Propolis from different areas has been reported to inhibit oncogenic/aging kinase PAK1, which is responsible for a variety of conditions, including cancer, longevity, and melanogenesis. Here, a crude extract of Okinawa propolis (OP) was tested against PAK1 activity, Caenorhabditis elegans (C. elegans) longevity, melanogenesis, and growth of cancer cells. We found that OP blocks PAK1 and exhibits anticancer activity in the A549 cell (human lung cancer cell) line with IC50 values of 6 μg/mL and 12 μg/mL, respectively. Most interestingly, OP (1 μg/mL) significantly reduces reproduction and prolongs the lifespan of C. elegans by activating the HSP-16.2 gene, as shown in the PAK1-deficient strain. Furthermore, OP inhibits melanogenesis in a melanoma cell line (B16F10) by downregulating intracellular tyrosinase activity with an IC50 of 30 μg/mL. Our results suggest that OP demonstrated a life span extending effect, C. elegans, anticancer, and antimelanogenic effects via PAK1 inactivation; therefore, this can be a potent natural medicinal supplement against PAK1-dependent diseases.
- Published
- 2016
- Full Text
- View/download PDF
36. Artepillin C and Other Herbal PAK1-blockers: Effects on Hair Cell Proliferation and Related PAK1-dependent Biological Function in Cell Culture.
- Author
-
Nguyen BC, Taira N, Maruta H, and Tawata S
- Subjects
- Animals, Brazil, Cell Line, Tumor, Cell Proliferation drug effects, Cells, Cultured, Hair Follicle cytology, Humans, Lim Kinases antagonists & inhibitors, Melanins biosynthesis, Melanoma, Experimental pathology, Mice, Momordica charantia chemistry, Pyrones pharmacology, Triterpenes pharmacology, Alpinia chemistry, Hair Follicle drug effects, Phenylpropionates pharmacology, p21-Activated Kinases antagonists & inhibitors
- Abstract
PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic kinase, and a number of herbal PAK1-blockers such as propolis and curcumin have been shown to be anti-oncogenic and anti-melanogenic as well as anti-alopecia (promoting hair growth). Previously, we found several distinct PAK1-inhibitors in Okinawa plants including Alpinia zerumbet (alpinia). Thus, here, we tested the effects of these herbal compounds and their derivatives on the growth of cancer or normal hair cells, and melanogenesis in cell culture of A549 lung cancer, hair follicle dermal papilla cell, and B16F10 melanoma. Among these herbal PAK1-inhibitors, cucurbitacin I from bitter melon (Goya) turned out to be the most potent to inhibit the growth of human lung cancer cells with the IC50 around 140 nM and to promote the growth of hair cells with the effective dose around 10 nM. Hispidin, a metabolite of 5,6-dehydrokawain from alpinia, inhibited the growth of cancer cells with the IC50 of 25 μM as does artepillin C, the major anti-cancer ingredient in Brazilian green propolis. Mimosine tetrapeptides (MFWY, MFYY, and MFFY) and hispidin derivatives (H1-3) also exhibited a strong anti-cancer activity with the IC50 ranging from 16 to 30 μM. Mimosine tetrapeptides and hispidin derivatives strongly suppressed the melanogenesis in melanoma cells., (Copyright © 2015 John Wiley & Sons, Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
37. Insecticidal and Nematicidal Activities of Novel Mimosine Derivatives.
- Author
-
Nguyen BC, Chompoo J, and Tawata S
- Subjects
- Acetylcholinesterase chemistry, Animals, Antinematodal Agents chemistry, Fabaceae chemistry, Insecticides chemistry, Mimosine chemistry, Pesticides chemistry, Plant Leaves chemistry, Antinematodal Agents pharmacology, Caenorhabditis elegans drug effects, Insecticides pharmacology, Mimosine pharmacology, Pesticides pharmacology, Plant Extracts pharmacology
- Abstract
Mimosine, a non-protein amino acid, is found in several tropical and subtropical plants, which has high value for medicine and agricultural chemicals. Here, in continuation of works aimed to development of natural product-based pesticidal agents, we present the first significant findings for insecticidal and nematicidal activities of novel mimosine derivatives. Interestingly, mimosinol and deuterated mimosinol (D-mimosinol) from mimosine had strong insecticidal activity which could be a result of tyrosinase inhibition (IC50 = 31.4 and 46.1 μM, respectively). Of synthesized phosphoramidothionate derivatives from two these amino alcohols, two compounds (1a and 1b) showed high insecticidal activity (LD50 = 0.5 and 0.7 μg/insect, respectively) with 50%-60% mortality at 50 μg/mL which may be attributed to acetylcholinesterase inhibition. Compounds 1a and 1b also had strong nematicidal activity with IC50 = 31.8 and 50.2 μM, respectively. Our results suggest that the length of the alkyl chain and the functional group at the C₅-position of phosphoramidothionates derived from mimosinol and d-mimosinol are essential for the insecticidal and nematicidal activities. These results reveal an unexplored scaffold as new insecticide and nematicide.
- Published
- 2015
- Full Text
- View/download PDF
38. Mimosine Dipeptide Enantiomsers: Improved Inhibitors against Melanogenesis and Cyclooxygenase.
- Author
-
Nguyen BC and Tawata S
- Subjects
- Animals, Cell Line, Tumor, Dose-Response Relationship, Drug, Down-Regulation, Hyperpigmentation drug therapy, Melanins biosynthesis, Melanoma, Experimental drug therapy, Melanoma, Experimental enzymology, Melanoma, Experimental metabolism, Mice, Mimosine chemistry, Monophenol Monooxygenase antagonists & inhibitors, Monophenol Monooxygenase metabolism, Prostaglandin-Endoperoxide Synthases chemistry, Prostaglandin-Endoperoxide Synthases metabolism, Signal Transduction drug effects, Skin metabolism, Stereoisomerism, Cyclooxygenase Inhibitors chemistry, Cyclooxygenase Inhibitors pharmacology, Dipeptides chemistry, Dipeptides pharmacology, Melanins antagonists & inhibitors, Mimosine analogs & derivatives, Mimosine pharmacology
- Abstract
Melanogenesis plays an important role in the protection of skin against UV through production of melanin pigments, but abnormal accumulation of this pigment causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we show for the first time that a small library of mimosine dipeptide enantiomers (Mi-L/D-amino acid) inhibit the melanogenesis in B16F10 melanoma cells by down-regulating the cellular tyrosinase with little effect on their growth or viability. Two of them, Mi-D-Trp and Mi-D-Val, turned out to be the most potent inhibitors on melanin content and cellular tyrosinase in B16F10 melanoma cells. In addition, most of the mimosine dipeptides were more potent than mimosine for inhibiting cyclooxygenase 1 (COX-1) with IC50 of 18-26 μM. Among them, Mi-L-Val and Mi-L-Trp inhibited cyclooxygenase 2 (COX-2) more potently than indomethacin, with IC50 values of 22 and 19 μM, respectively. Taken together, our results suggest the possibility that mimosine dipeptides could be better candidates (than mimosine) for anti-melanogenic (skin hyperpigmentation treatment) and cyclooxygenase (COX) inhibition.
- Published
- 2015
- Full Text
- View/download PDF
39. Combination of immunoprecipitation (IP)-ATP_Glo kinase assay and melanogenesis for the assessment of potent and safe PAK1-blockers in cell culture.
- Author
-
Nguyen BC, Be Tu PT, Tawata S, and Maruta H
- Subjects
- Animals, Caffeic Acids pharmacology, Cell Line, Tumor, Humans, Immunoprecipitation, Mice, Phenylethyl Alcohol analogs & derivatives, Phenylethyl Alcohol pharmacology, Triterpenes pharmacology, Antineoplastic Agents pharmacology, Melanins biosynthesis, Protein Kinase Inhibitors pharmacology, Reagent Kits, Diagnostic, p21-Activated Kinases antagonists & inhibitors
- Abstract
Cucurbitacin I (CBI) is a triterpene from a bitter melon called Goya grown in Okinawa, Japan, and directly inhibits both the Tyr-kinase JAK2 and the G protein RAC, leading to the inactivation of PAK1 (RAC/CDC42-activated kinase 1). Bio 30, a propolis produced in New Zealand, contains CAPE (caffeic acid phenethyl ester) as the major anti-cancer ingredient which directly down-regulates RAC, leading to the inactivation of PAK1. Since PAK1 is essential for the growth of RAS cancer cells such as A549 cell line which carry an oncogenic K-RAS mutant, and the melanogenesis in skin cells, here using these PAK1-blockers as model compounds, we introduce a new approach to the quick assessment of PAK1-blockers in cell culture. First, combining the immuno-precipitation (IP) of PAK1 from cell lysate and the in vitro ATP_Glo kinase assay kit (called "Macaroni-Western" assay), we confirmed that both CBI and Bio 30 inactivate PAK1 in A549 lung cancer cells in 24 h, and inhibit their PAK1-dependent growth in 72 h. Furthermore, we verified that CBI inhibits the PAK1/PAK4-dependent melanogenesis in melanoma cells by far more than 50%, while Bio 30 inhibits the melanogenesis only by 50%, with only a merginal effect on their growth per se. Since the "Macaroni-Western" kinase assay and melanogenesis are both rather simple and quick, the combination of these two cell culture assays would be highly useful for selecting both "potent" (highly cell-permeable) and "safe" (non-toxic) natural or synthetic PAK1-blockers.
- Published
- 2015
- Full Text
- View/download PDF
40. Several herbal compounds in Okinawa plants directly inhibit the oncogenic/aging kinase PAK1.
- Author
-
Nguyen BC, Taira N, and Tawata S
- Subjects
- Humans, Japan, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors isolation & purification, Aging drug effects, Neoplasms enzymology, Plants, Medicinal chemistry, Protein Kinase Inhibitors pharmacology, p21-Activated Kinases antagonists & inhibitors
- Abstract
The p21-activated kinase 1 (PAK1) is emerging as a promising therapeutic target, and the search for blockers of this oncogenic/aging kinase would be potentially useful for the treatment of various diseases/disorders in the future. Here, we report for the first time the anti-PAK1 activity of compounds derived from three distinct Okinawa plants. 5,6-Dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK) from alpinia inhibited directly PAK1 more strongly than mimosine and mimosinol from leucaena. Cucurbitacin I isolated from bitter gourd/melon also exhibited a moderate anti-PAK1 activity. Hispidin, a metabolite of DK, strongly inhibited PAK1 with the IC50 = 5.7 μM. The IC50 of three hispidin derivatives (H1-3) for PAK1 inhibition ranges from 1.2 to 2.0 μM, while mimosine tetrapeptides [mimosine-Phe-Phe-Tyr (MFFY) and mimosine-Phe-Trp-Tyr (MFWY)] inhibit PAK1 at nanomolar level (IC50 of 0.13 and 0.60 μM, respectively). Thus, we hope these derivatives of hispidin and mimosine could be used as potential leading compounds for developing far more potent anti-PAK1 drugs which would be useful for clinical application in the future.
- Published
- 2014
- Full Text
- View/download PDF
41. Pax6 mediates ß-catenin signaling for self-renewal and neurogenesis by neocortical radial glial stem cells.
- Author
-
Gan Q, Lee A, Suzuki R, Yamagami T, Stokes A, Nguyen BC, Pleasure D, Wang J, Chen HW, and Zhou CJ
- Subjects
- Animals, Cell Differentiation physiology, Cell Growth Processes physiology, Mice, Mice, Transgenic, Neocortex metabolism, Neural Stem Cells metabolism, Neuroglia cytology, Neuroglia metabolism, PAX6 Transcription Factor, Signal Transduction, Transfection, Wnt Signaling Pathway, beta Catenin genetics, Eye Proteins metabolism, Homeodomain Proteins metabolism, Neocortex cytology, Neural Stem Cells cytology, Neurogenesis physiology, Paired Box Transcription Factors metabolism, Repressor Proteins metabolism, beta Catenin metabolism
- Abstract
The Wnt/ß-catenin pathway is a critical stem cell regulator and plays important roles in neuroepithelial cells during early gestation. However, the role of Wnt/ß-catenin signaling in radial glia, a major neural stem cell population expanded by midgestation, remains poorly understood. This study shows that genetic ablation of ß-catenin with hGFAP-Cre mice inhibits neocortical formation by disrupting radial glial development. Reduced radial glia and intermediate progenitors are found in the ß-catenin-deficient neocortex during late gestation. Increased apoptosis and divergent localization of radial glia in the subventricular zone are also observed in the mutant neocortex. In vivo and in vitro proliferation and neurogenesis as well as oligodendrogenesis by cortical radial glia or by dissociated neural stem cells are significantly defective in the mutants. Neocortical layer patterning is not apparently altered, while astrogliogenesis is ectopically increased in the mutants. At the molecular level, the expression of the transcription factor Pax6 is dramatically diminished in the cortical radial glia and the sphere-forming neural stem cells of ß-catenin-deficient mutants. Chromatin immunoprecipitation and luciferase assays demonstrate that ß-catenin/Tcf complex binds to Pax6 promoter and induces its transcriptional activities. The forced expression of Pax6 through lentiviral transduction partially rescues the defective proliferation and neurogenesis by ß-catenin-deficient neural stem cells. Thus, Pax6 is a novel downstream target of the Wnt/ß-catenin pathway, and ß-catenin/Pax6 signaling plays critical roles in self-renewal and neurogenesis of radial glia/neural stem cells during neocortical development., (© AlphaMed Press.)
- Published
- 2014
- Full Text
- View/download PDF
42. IRF6 is a mediator of Notch pro-differentiation and tumour suppressive function in keratinocytes.
- Author
-
Restivo G, Nguyen BC, Dziunycz P, Ristorcelli E, Ryan RJ, Özuysal ÖY, Di Piazza M, Radtke F, Dixon MJ, Hofbauer GF, Lefort K, and Dotto GP
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Cycle Proteins metabolism, Cell Differentiation, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Cyclin-Dependent Kinase Inhibitor p21 physiology, DNA-Binding Proteins metabolism, ErbB Receptors biosynthesis, ErbB Receptors genetics, Genes, Tumor Suppressor, Homeodomain Proteins metabolism, Humans, Interferon Regulatory Factors biosynthesis, Interferon Regulatory Factors genetics, Keratinocytes cytology, Keratinocytes metabolism, Mice, Mice, Inbred NOD, Mice, SCID, Oncogene Protein p21(ras) metabolism, Promoter Regions, Genetic, RNA Interference, RNA, Small Interfering, Receptor, Notch1 genetics, Signal Transduction, Skin Neoplasms metabolism, Skin Neoplasms pathology, Transcription Factor HES-1, Interferon Regulatory Factors metabolism, Keratinocytes physiology, Receptor, Notch1 metabolism
- Abstract
While the pro-differentiation and tumour suppressive functions of Notch signalling in keratinocytes are well established, the underlying mechanisms remain poorly understood. We report here that interferon regulatory factor 6 (IRF6), an IRF family member with an essential role in epidermal development, is induced in differentiation through a Notch-dependent mechanism and is a primary Notch target in keratinocytes and keratinocyte-derived SCC cells. Increased IRF6 expression contributes to the impact of Notch activation on growth/differentiation-related genes, while it is not required for induction of 'canonical' Notch targets like p21(WAF1/Cip1), Hes1 and Hey1. Down-modulation of IRF6 counteracts differentiation of primary human keratinocytes in vitro and in vivo, promoting ras-induced tumour formation. The clinical relevance of these findings is illustrated by the strikingly opposite pattern of expression of Notch1 and IRF6 versus epidermal growth factor receptor in a cohort of clinical SCCs, as a function of their grade of differentiation. Thus, IRF6 is a primary Notch target in keratinocytes, which contributes to the role of this pathway in differentiation and tumour suppression.
- Published
- 2011
- Full Text
- View/download PDF
43. Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis.
- Author
-
Hu B, Lefort K, Qiu W, Nguyen BC, Rajaram RD, Castillo E, He F, Chen Y, Angel P, Brisken C, and Dotto GP
- Subjects
- Animals, Gene Deletion, Keratinocytes metabolism, Mice, Wnt Proteins genetics, Wnt-5a Protein, Forkhead Transcription Factors metabolism, Hair Follicle, Immunoglobulin J Recombination Signal Sequence-Binding Protein metabolism, Signal Transduction, Wnt Proteins metabolism
- Abstract
Epithelial-mesenchymal interactions are key to skin morphogenesis and homeostasis. We report that maintenance of the hair follicle keratinocyte cell fate is defective in mice with mesenchymal deletion of the CSL/RBP-Jkappa gene, the effector of "canonical" Notch signaling. Hair follicle reconstitution assays demonstrate that this can be attributed to an intrinsic defect of dermal papilla cells. Similar consequences on hair follicle differentiation result from deletion of Wnt5a, a specific dermal papilla signature gene that we found to be under direct Notch/CSL control in these cells. Functional rescue experiments establish Wnt5a as an essential downstream mediator of Notch-CSL signaling, impinging on expression in the keratinocyte compartment of FoxN1, a gene with a key hair follicle regulatory function. Thus, Notch/CSL signaling plays a unique function in control of hair follicle differentiation by the underlying mesenchyme, with Wnt5a signaling and FoxN1 as mediators.
- Published
- 2010
- Full Text
- View/download PDF
44. Opposing roles for calcineurin and ATF3 in squamous skin cancer.
- Author
-
Wu X, Nguyen BC, Dziunycz P, Chang S, Brooks Y, Lefort K, Hofbauer GF, and Dotto GP
- Subjects
- Animals, Calcineurin deficiency, Calcineurin genetics, Calcineurin Inhibitors, Carcinoma, Squamous Cell chemically induced, Cell Line, Tumor, Cell Proliferation, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, Cells, Cultured, Cellular Senescence, Cyclosporine pharmacology, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Humans, Keratinocytes metabolism, Keratinocytes pathology, Mice, Mice, Inbred NOD, Mice, SCID, NFATC Transcription Factors antagonists & inhibitors, NFATC Transcription Factors deficiency, NFATC Transcription Factors genetics, NFATC Transcription Factors metabolism, Neoplasm Transplantation, Signal Transduction, Skin Neoplasms chemically induced, Tumor Suppressor Protein p53 metabolism, Activating Transcription Factor 3 metabolism, Calcineurin metabolism, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Skin Neoplasms metabolism, Skin Neoplasms pathology
- Abstract
Calcineurin inhibitors such as cyclosporin A (CsA) are the mainstay of immunosuppressive treatment for organ transplant recipients. Squamous cell carcinoma (SCC) of the skin is a major complication of treatment with these drugs, with a 65 to 100-fold higher risk than in the normal population. By contrast, the incidence of basal cell carcinoma (BCC), the other major keratinocyte-derived tumour of the skin, of melanoma and of internal malignancies increases to a significantly lesser extent. Here we report that genetic and pharmacological suppression of calcineurin/nuclear factor of activated T cells (NFAT) function promotes tumour formation in mouse skin and in xenografts, in immune compromised mice, of H-ras(V12) (also known as Hras1)-expressing primary human keratinocytes or keratinocyte-derived SCC cells. Calcineurin/NFAT inhibition counteracts p53 (also known as TRP53)-dependent cancer cell senescence, thereby increasing tumorigenic potential. ATF3, a member of the 'enlarged' AP-1 family, is selectively induced by calcineurin/NFAT inhibition, both under experimental conditions and in clinically occurring tumours, and increased ATF3 expression accounts for suppression of p53-dependent senescence and enhanced tumorigenic potential. Thus, intact calcineurin/NFAT signalling is critically required for p53 and senescence-associated mechanisms that protect against skin squamous cancer development.
- Published
- 2010
- Full Text
- View/download PDF
45. Elastic behavior of methyltrimethoxysilane based aerogels reinforced with tri-isocyanate.
- Author
-
Nguyen BC, Meador MA, Medoro A, Arendt V, Randall J, McCorkle L, and Shonkwiler B
- Subjects
- Air, Elastic Modulus, Materials Testing, Gels chemistry, Isocyanates chemistry, Silanes chemistry
- Abstract
The elastic properties and/or flexibility of polymer reinforced silica aerogels having methyltrimethoxysilane (MTMS) and bis(trimethoxysilylpropyl)amine (BTMSPA) making up the silica structure are examined. The dipropylamine spacer from BTMSPA is used both to provide a flexible linking group in the silica structure, and as a reactive site via its secondary amine for reaction with a tri-isocyanate, Desmodur N3300A. The tri-isocyanate provides an extended degree of branching or reinforcement, resulting in increased compressive strength of the aerogel monoliths while the overall flexibility arising from the underlying silica structure is maintained. The compressive moduli of the reinforced aerogel monoliths in this study range from 0.001 to 158 MPa. Interestingly, formulations across this entire range of modulus recover nearly all of their length after two compressions to 25% strain. Differences in pore structure of the aerogels due to processing conditions and solvent are also discussed.
- Published
- 2010
- Full Text
- View/download PDF
46. Cooperation between the transcription factors p63 and IRF6 is essential to prevent cleft palate in mice.
- Author
-
Thomason HA, Zhou H, Kouwenhoven EN, Dotto GP, Restivo G, Nguyen BC, Little H, Dixon MJ, van Bokhoven H, and Dixon J
- Subjects
- Animals, Binding Sites, Enhancer Elements, Genetic, Epistasis, Genetic, Genetic Variation, Heterozygote, Keratinocytes cytology, Mice, Models, Biological, Transcriptional Activation, Cleft Palate metabolism, Gene Expression Regulation, Developmental, Interferon Regulatory Factors genetics, Interferon Regulatory Factors metabolism, Mutation, Phosphoproteins genetics, Phosphoproteins metabolism, Trans-Activators genetics, Trans-Activators metabolism
- Abstract
Cleft palate is a common congenital disorder that affects up to 1 in 2,500 live human births and results in considerable morbidity to affected individuals and their families. The etiology of cleft palate is complex, with both genetic and environmental factors implicated. Mutations in the transcription factor-encoding genes p63 and interferon regulatory factor 6 (IRF6) have individually been identified as causes of cleft palate; however, a relationship between the key transcription factors p63 and IRF6 has not been determined. Here, we used both mouse models and human primary keratinocytes from patients with cleft palate to demonstrate that IRF6 and p63 interact epistatically during development of the secondary palate. Mice simultaneously carrying a heterozygous deletion of p63 and the Irf6 knockin mutation R84C, which causes cleft palate in humans, displayed ectodermal abnormalities that led to cleft palate. Furthermore, we showed that p63 transactivated IRF6 by binding to an upstream enhancer element; genetic variation within this enhancer element is associated with increased susceptibility to cleft lip. Our findings therefore identify p63 as a key regulatory molecule during palate development and provide a mechanism for the cooperative role of p63 and IRF6 in orofacial development in mice and humans.
- Published
- 2010
- Full Text
- View/download PDF
47. p21WAF1/Cip1 suppresses keratinocyte differentiation independently of the cell cycle through transcriptional up-regulation of the IGF-I gene.
- Author
-
Devgan V, Nguyen BC, Oh H, and Dotto GP
- Subjects
- Animals, Cell Cycle, Cell Differentiation, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Enzyme Activation, Epidermis metabolism, Insulin-Like Growth Factor I genetics, Keratinocytes metabolism, MAP Kinase Signaling System, Mice, Promoter Regions, Genetic, Transcription, Genetic, Cyclin-Dependent Kinase Inhibitor p21 physiology, Gene Expression Regulation, Insulin-Like Growth Factor I biosynthesis, Keratinocytes cytology
- Abstract
p21 plays a dual role in keratinocyte growth and differentiation control. It restricts the number of keratinocyte stem cell populations while inhibiting the later stages of differentiation independently of the cell cycle. The molecular/biochemical mechanism for the differentiation suppressive function of p21 is unknown. Here we show that elevated p21 expression leads to activation of MAPK family members in a keratinocyte-specific and cell cycle-independent manner, and up-regulation of MAPK activity can explain the inhibitory effects of p21 on differentiation. p21 induces transcription of several genes with MAPK activation potential. Although several of these genes are induced by p21 in a MAPK-dependent manner, expression of IGF-I is induced upstream of MAPK activation. IGF-I stimulation is by itself sufficient to cause MAPK activation and inhibit differentiation and suppression of IGF-I signaling by knock down of the cognate receptor (IGF-R1), diminishing the ability of p21 to activate MAPK and suppress differentiation. Thus, in keratinocytes, the ability of p21 to suppress differentiation can be explained by cell type-specific activation of the MAPK cascade by transcriptional up-regulation of the IGF-I gene.
- Published
- 2006
- Full Text
- View/download PDF
48. Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation.
- Author
-
Nguyen BC, Lefort K, Mandinova A, Antonini D, Devgan V, Della Gatta G, Koster MI, Zhang Z, Wang J, Tommasi di Vignano A, Kitajewski J, Chiorino G, Roop DR, Missero C, and Dotto GP
- Subjects
- Animals, Base Sequence, DNA Primers, Humans, Mice, Promoter Regions, Genetic, RNA, Small Interfering, Transcription Factors, Cell Differentiation physiology, DNA-Binding Proteins physiology, Keratinocytes cytology, Receptor, Notch1 physiology, Trans-Activators physiology, Tumor Suppressor Proteins physiology
- Abstract
Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.
- Published
- 2006
- Full Text
- View/download PDF
49. High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism.
- Author
-
Okuyama R, Nguyen BC, Talora C, Ogawa E, Tommasi di Vignano A, Lioumi M, Chiorino G, Tagami H, Woo M, and Dotto GP
- Subjects
- Animals, Animals, Newborn, Caspase 3, Caspases genetics, Cell Lineage genetics, Cells, Cultured, Epidermal Cells, Fetus, In Vitro Techniques, Keratinocytes cytology, Mice, Protein Kinase C genetics, Protein Kinase C metabolism, Protein Kinase C-delta, Receptor, Notch1, Receptors, Cell Surface genetics, Signal Transduction drug effects, Signal Transduction physiology, Up-Regulation genetics, Caspases metabolism, Cell Differentiation genetics, Epidermis embryology, Epidermis growth & development, Keratinocytes metabolism, Receptors, Cell Surface metabolism, Transcription Factors
- Abstract
Embryonic cells are expected to possess high growth/differentiation potential, required for organ morphogenesis and expansion during development. However, little is known about the intrinsic properties of embryonic epithelial cells due to difficulties in their isolation and cultivation. We report here that pure keratinocyte populations from E15.5 mouse embryos commit irreversibly to differentiation much earlier than newborn cells. Notch signaling, which promotes keratinocyte differentiation, is upregulated in embryonic keratinocyte and epidermis, and elevated caspase 3 expression, which we identify as a transcriptional Notch1 target, accounts in part for the high commitment of embryonic keratinocytes to terminal differentiation. In vivo, lack of caspase 3 results in increased proliferation and decreased differentiation of interfollicular embryonic keratinocytes, together with decreased activation of PKC-delta, a caspase 3 substrate which functions as a positive regulator of keratinocyte differentiation. Thus, a Notch1-caspase 3 regulatory mechanism underlies the intrinsically high commitment of embryonic keratinocytes to terminal differentiation.
- Published
- 2004
- Full Text
- View/download PDF
50. Factors influencing sunless tanning with dihydroxyacetone.
- Author
-
Nguyen BC and Kochevar IE
- Subjects
- Dermatologic Agents metabolism, Dihydroxyacetone metabolism, Epidermis metabolism, Humans, Humidity, Hydrogen-Ion Concentration, Oxygen pharmacology, Spectrometry, Fluorescence, Sunscreening Agents chemistry, Amino Acids metabolism, Dermatologic Agents pharmacology, Dihydroxyacetone pharmacology, Skin Pigmentation drug effects
- Abstract
Background: Sunless tanning preparations have been used for more than 50 years and are still very popular because they provide temporary pigmentation resembling an ultraviolet-induced tan. The pigment is the product of reactions between dihydroxyacetone (DHA) and amino acids in the stratum corneum., Objectives: To understand the factors that influence the reactions of DHA with amino acids in the stratum corneum with the ultimate goal of producing pigmentation with greater photoprotection., Methods: The influence of hydration and/or oxygen on the development of DHA-induced pigment was assessed in vivo using an occlusive dressing and ex vitro on human epidermal preparations. Two spectroscopic techniques, diffuse reflectance and fluorescence emission, were used to monitor the extent of pigment development. The optimal relative humidity for DHA-induced pigmentation was assessed on the epidermal preparations. The formation of products from reactions between DHA and nine amino acids was studied in solutions buffered at pH 5 and 7., Results: Development of DHA-induced pigmentation was inhibited by a 24-h occlusive dressing but appeared after its removal, indicating that DHA was still present. High hydration but not the absence of oxygen inhibited coloration of occluded skin. The extent of pigmentation did not vary in a simple manner with hydration, as pigment formation was positively correlated with humidity from 0 to 75% but negatively correlated from 75 to 100%. Lysine, glycine and histidine reacted most rapidly with DHA, with reaction rates greater at pH 7 than at pH 5. The products absorbed with maxima at wavelengths up to 340 nm., Conclusions: These results indicate that extent of hydration, pH and availability of certain amino acids influence the development of DHA-induced pigmentation in the stratum corneum and suggest that manipulation of these factors might produce pigmentation with greater photoprotection.
- Published
- 2003
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.