The phytochemical quercetin has gained attention for its antiinflammatory and anti-tumorigenic properties in various types of cancer. Tumorigenesis involves the aberrant regulation of ...kinase/phosphatase, highlighting the importance of maintaining homeostasis. Dual Specificity Phosphatase (DUSP) plays a crucial role in controlling the phosphorylation of ERK. The current study aimed to clone the DUSP5 promoter, and investigate its transcriptional activity in the presence of quercetin. The results revealed that quercetin-induced DUSP5 expression is associated with the serum response factor (SRF) binding site located in the DUSP5 promoter. The deletion of this site abolished the luciferase activity induced by quercetin, indicating its vital role in quercetin-induced DUSP5 expression. SRF protein is a transcription factor that potentially contributes to quercetin- induced DUSP5 expression at the transcriptional level. Additionally, quercetin enhanced SRF binding activity without changing its expression. These findings provide evidence of how quercetin affects anti-cancer activity in colorectal tumorigenesis by inducing SRF transcription factor activity, thereby increasing DUSP5 expression at the transcriptional level. This study highlights the importance of investigating the molecular mechanisms underlying the anti-cancer properties of quercetin, and suggests its potential use in cancer therapy. BMB Reports 2023; 56(9): 508-513
Hair loss or alopecia is an unpleasant symptom that exacerbates an individual's self-esteem and requires appropriate treatment. The Wnt/β-catenin signaling is a central pathway that promotes dermal ...papilla induction and keratinocyte proliferation during hair follicle renewal. GSK-3β inactivated by its upstream Akt and ubiquitin-specific protease 47 (USP47) has been shown to inhibit β-catenin degradation. The cold atmospheric microwave plasma (CAMP) is microwave energy enriched with mixtures of radicals. CAMP has been reported to have antibacterial and antifungal activities with wound healing activity against skin infection; however, the effect of CAMP on hair loss treatment has not been reported. We aimed to investigate the effect of CAMP on promoting hair renewal in vitro and to elucidate the molecular mechanism, targeting β-catenin signaling and YAP/TAZ, the co-activators in the Hippo pathway, in human dermal papilla cells (hDPCs). We also evaluated plasma effects on the interaction between hDPCs and HaCaT keratinocytes. The hDPCs were treated with plasma-activating media (PAM) or gas-activating media (GAM). The biological outcomes were determined by MTT assay, qRT-PCR, western blot analysis, immunoprecipitation, and immunofluorescence. We found that β-catenin signaling and YAP/TAZ were significantly increased in PAM-treated hDPCs. PAM treatment also induced β-catenin translocation and inhibited β-catenin ubiquitination by activating Akt/GSK-3β signaling and upregulating USP47 expression. In addition, hDPCs were more aggregated with keratinocytes in PAM-treated cells compared with control. HaCaT cells cultured in a conditioned medium derived from PAM-treated hDPCs exhibited an enhancing effect on activating YAP/TAZ and β-catenin signaling. These findings suggested that CAMP may be a new therapeutic alternative for alopecic treatment.
A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is ...unknown.
Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays.
Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity.
In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neuroinflammation is a brain pathology that involves the expression of high levels of pro-inflammatory mediators, including tumor necrosis factor-alpha (TNF-α). An excessive TNF-α expression could ...result in neuronal cell death and subsequently lead to neurodegeneration. Auricularia polytricha (AP; an edible mushroom) has been reported as a rich source of ergosterol with several medicinal benefits. The current study reports on the neuroprotective effects of AP extracts and ergosterol against the TNF-α-induced HT-22 hippocampal cell injury. The hexane extract of AP (APH) demonstrated a neuroprotective effect against the TNF-α-induced HT-22 cell toxicity, taking place through the activation of the antioxidant pathway. Ergosterol, a major component of APH, could attenuate the toxicity of TNF-α on HT-22 cells, by increasing the expression of a major antioxidant enzyme (superoxide dismutase-1) and by facilitating the scavenging of reactive oxygen species through antioxidant signaling. Moreover, an antibody array was performed to screen the possible molecular targets of ergosterol in HT-22 cells exposed to TNF-α. Based on the antibody array, the phospho-Akt was activated in the presence of ergosterol, and this finding was also supported by Western blotting analysis. Furthermore, ergosterol inhibited the transcriptional expressions of the glutamate ionotropic receptor N-methyl-D-aspartate (NMDA) type subunit 2B gene (Grin2b) through an early growth response-1 (EGR-1) overexpression in TNF-α-treated HT-22 cells. Our findings suggest that a novel therapeutic effect of AP and ergosterol against neuroinflammation, that it is mediated by an NMDA gene modulation occurring through the overexpression of the EGR-1 transcription factor.
Display omitted
•Auricularia polytricha mushroom extract and its major component, ergosterol attenuated TNF-α-induced hippocampal injury.•The mushroom extract and ergosterol exhibited antioxidant activity by increasing SOD-1 expression.•Ergosterol promoted neuronal survival in TNF-α-exposed HT-22 cells via the Akt/GSK-3β signaling.•Ergosterol inhibited Grin2b transcription through an EGR-1 expression in TNF-α-exposed HT-22 cells.
The stem bark of
(Roxb.) Planch. has been applied for the treatment of human cutaneous diseases as well as canine demodicosis in several countries. However, no detailed mechanistic studies have been ...reported to support their use. In this study, thin-layer chromatography and gas chromatography were used to screen phytochemicals from the fresh stem bark extract of
. We found the two major bioactive compounds, friedelin and lupeol, and their activity on wound healing was further investigated in keratinocytes. Both bioactive compounds significantly reduced wound area and increased keratinocyte migration by increasing matrix metalloproteinases-9 production. Subsequently, we found that the mRNA gene expressions of cadherin 1 and desmoglobin 1 significantly decreased, whereas the gene expression involved in keratinocyte proliferation and homeostasis (keratin-17) increased in compound-treated human immortalized keratinocytes cells. The expression of inflammatory genes (cyclooxygenase-2 and inducible nitric oxide synthase) and pro-inflammatory cytokine genes (tumor necrosis factor-alpha and interleukin-6) was reduced by treatment with
-hexane extract of
and its bioactive compounds. Our results revealed that
extract and its bioactive compounds, friedelin and lupeol, exhibit wound-healing activity with anti-inflammatory properties, mediated by regulating the gene expression involved in skin re-epithelialization.
This study proposes an effective repair technology using arc additive manufacturing for pressurized water reactors (PWRs) in nuclear power plants (NPP) aimed at avoiding complete replacements and ...post-weld-heat treatments (PWHTs) of component parts while ensuring safety and reliability. Effective repair technology is defined as economic and process efficiency, because of maintenance costs and radiation exposure, and it is critical in related industries. The technology is designed to relieve the hardness and martensite fraction of the welding heat affected zone (HAZ) of low alloy steels (SA508) in PWRs penetration/nozzles by heat source generated in the WAAM process, thus ensuring structural integrity. In the first layer of wire arc additive manufacturing processes, 89.6% of the martensite phase was formed in the HAZ of SA508, which was significantly reduced to 45.7% due to repetitive thermal behaviors at the third layer. The resulting process dramatically reduced hardness from 450Hv in the initial layer additive manufacturing to 320Hv in 3 layers without additional heat treatments. Moreover, the study quantitatively investigated the martensite starting temperature (Ms) and bainite starting temperature (Bs) and analyzed the microstructure and mechanical behavior of the developed process using thermodynamic calculation (CALPHAD), finite element method (FEM) simulation, and microstructure quantitative analysis by electron backs-catter diffraction (EBSD). The proposed technologies and their quantitative analysis results can be a substantial alternative to the repair technology for penetration/nozzles in nuclear primary water cooling reactor applications, complying with ASME Sec.IX Qw-462.12 and ISO 15614-1.
Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases including cancer. Although ...noni has been consumed for a long time in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In this report, we examined systematic approaches on the cancer-suppressing capability of damnacanthal in colorectal tumorigenesis. Damnacanthal exhibits cell growth arrest as well as caspase activity induction in colorectal cancer cells. We also examined several potential target proteins and found that the proapoptotic protein nonsteroidal anti-inflammatory activated gene-1 (NAG-1) is highly induced. Subsequently, we have found that damnacanthal also enhances transcription factor CCAAT/enhancer binding protein β (C/EBPβ), which controls NAG-1 transcriptional activity. Blocking of C/EBPβ by shRNA results in the reduction of NAG-1 expression as well as caspase activity in the presence of damnacanthal. Taken together, these results indicate that damnacanthal increases antitumorigenic activity in human colorectal cancer cells and that C/EBPβ plays a role in damnacanthal-induced NAG-1 expression.
Purpose
The public has paid attention to green tea due to its health benefits. Epigallocatechin-3-gallate (EGCG), the major component of green tea, is well documented to induce apoptosis and cell ...cycle arrest in cancer cells by targeting multiple signal transduction pathways. However, the detailed mechanism(s) of action needs to be determined.
Methods
Cell growth was evaluated by MTT assay, cell cycle analysis, and caspase 3/7 activity. Protein expression was analyzed through Western blotting. Reverse transcription polymerase chain reaction was used for examining mRNA expression of p21 and cyclin D1. The promoter activity of p21 was assessed by the luciferase reporter system.
Results
We identified cyclin D1 and p21 as molecular targets of EGCG in human colorectal cancer cells. We observed that cyclin D1 was down-regulated, while p21 expression was up-regulated by EGCG in dose- and time-dependent manners. Furthermore, we found EGCG decreased cyclin D1 protein stability, therefore triggering ubiquitin-dependent proteasomal degradation. Meanwhile, EGCG increased p21 promoter activity, resulting in up-regulation of p21 mRNA and protein, which was likely dependent on extracellular-signal-regulated kinase (ERK), inhibitor of nuclear factor kappa-B kinase (IKK) and phosphoinositide 3-kinase (PI3 K).
Conclusion
The data presented here details a novel mechanism by which EGCG inhibits cell growth of colorectal cancer cells. Namely, EGCG-induced cyclin D1 degradation and p21 transcriptional activation partially contribute to growth suppression in these cells.
Background
The antifungal efficacy of cold atmospheric microwave plasma (CAMP) against Malassezia pachydermatis has not been to be evaluated.
Objective
To examine the antifungal effects of CAMP ...against M. pachydermatis and its synergistic effects with chlorhexidine gluconate (CHX).
Methods
A M. pachydermatis isolate was collected from a dog with otitis externa and Malassezia dermatitis at the Seoul National University Veterinary Medical Teaching Hospital. The antifungal effect was determined by applying CAMP to a M. pachydermatis isolate that was incubated for 3 days at 37°C. After 1, 2, 3 and 5 min of application, the efficacy of the plasma treatment was determined according to the number of colony forming units (CFUs). A mixture consisting of inoculum and CHX was applied to evaluate the synergistic effect of the plasma treatment in the same way.
Results
The application of CAMP showed significant antifungal effects against M. pachydermatis. The antifungal effect of CAMP was enhanced by an increased exposure time and output power. The application of CAMP with 0.02% and 0.2% CHX resulted in lower survival rates against M. pachydermatis when compared with its sole application at 1 or 2 min.
Conclusions
The study findings demonstrate that CAMP has a potential as a new antifungal option for M. pachydermatis and has synergistic antifungal effects with CHX in vitro. Clinical applications for CAMP are necessary to assess the antifungal efficacy for patients.
Cold atmospheric microwave plasma (CAMP) caused a significant antifungal effect against Malassezia pachydermatis and also showed a synergistic activity with chlorhexidine gluconate (CHX) against M. pachydermatis.
A comparative study on the three quantitative methods frequently used in proteomics, 2D DIGE (difference gel electrophoresis), cICAT (cleavable isotope-coded affinity tags) and iTRAQ (isobaric tags ...for relative and absolute quantification), was carried out. DIGE and cICAT are familiar techniques used in gel- and LC-based quantitative proteomics, respectively. iTRAQ is a new LC-based technique which is gradually gaining in popularity. A systematic comparison among these quantitative methods has not been reported. In this study, we conducted well-designed comparisons using a six-protein mixture, a reconstituted protein mixture (BSA spiked into human plasma devoid of six abundant proteins), and complex HCT-116 cell lysates as the samples. All three techniques yielded quantitative results with reasonable accuracy when the six-protein or the reconstituted protein mixture was used. In DIGE, accurate quantification was sometimes compromised due to comigration or partial comigration of proteins. The iTRAQ method is more susceptible to errors in precursor ion isolation, which could be manifested with increasing sample complexity. The quantification sensitivity of each method was estimated by the number of peptides detected for each protein. In this regard, the global-tagging iTRAQ technique was more sensitive than the cysteine-specific cICAT method, which in turn was as sensitive as, if not more sensitive than, the DIGE technique. Protein profiling on HCT-116 and HCT-116 p53 −/− cell lysates displayed limited overlapping among proteins identified by the three methods, suggesting the complementary nature of these methods. Keywords: protein quantification • DIGE • cICAT • iTRAQ • 2D gel • LC-MALDI TOF/TOF
PDF
