• Microbiology and Biotechnology Letters
• /
• v.24 no.2
• /
• pp.242-246
• /
• 1996

Hatomarubigins inhibited the growth of various cancer cell lines including multidrug-resistance cells. Hatomarubigins were found to potentiate the colchicine- and vinblastine-induced cytotoxicity against KB-C2 cell, but not the adriamycin-induced cytotoxicity against KB-C2 cells. Hatomarubigins didn't affect the sensitive KB cells. These results suggest that hatomarubigins are specific potentiators of colchicine. Among four hatomarubigins, hatomarubigin A sho- wed the highest synergestic effect on colchine-induced cytotoxicity. Similar effect of hatomarubigin A was found against V79/ADM cells.

• Biomolecules & Therapeutics
• /
• v.21 no.2
• /
• pp.114-120
• /
• 2013

Most patients with mutant B-Raf melanomas respond to inhibitors of oncogenic B-Raf but resistance eventually emerges. To better understand the mechanisms that determine the long-term responses of mutant B-Raf melanoma cells to B-Raf inhibitor, we used chronic selection to establish B-Raf (V600E) melanoma clones with acquired resistance to the new oncogenic B-Raf inhibitor UI-152. Whereas the parental A375P cells were highly sensitive to UI-152 ($IC_{50}$ < $0.5{\mu}M$), the resistant sub-line (A375P/Mdr) displayed strong resistance to UI-152 ($IC_{50}$ < $20{\mu}M$). Immunofluorescence analysis indicated the absence of an increase in the levels of P-glycoprotein multidrug resistance (MDR) transporter in A375P/Mdr cells, suggesting that resistance was not attributable to P-glycoprotein overexpression. In UI-152-sensitive A375P cells, the anti-proliferative activity of UI-152 appeared to be due to cell-cycle arrest at $G_0/G_1$ with the induction of apoptosis. However, we found that A375P/Mdr cells were resistant to the apoptosis induced by UI-152. Interestingly, UI-152 preferentially induced autophagy in A375P/Mdr cells but not in A375P cells, as determined by GFP-LC3 puncta/cell counts. Further, autophagy inhibition with 3-methyladenine (3-MA) partially augmented growth inhibition of A375P/Mdr cells by UI-152, which implies that a high level of autophagy may protect UI-152-treated cells from undergoing growth inhibition. Together, our data implicate high rates of autophagy as a key mechanism of acquired resistance to the oncogenic B-Raf inhibitor, in support of clinical studies in which combination therapy with autophagy targeted drugs is being designed to overcome resistance.

• Microbiology and Biotechnology Letters
• /
• v.52 no.3
• /
• pp.275-287
• /
• 2024

Insulin resistance is a primary risk factor for developing diabetes. However, diabetes drugs generally focus on regulating and lowering patients' blood glucose levels. In recent years, diverse materials have been evaluated to improve insulin resistance and hinder the development of diabetes. Momordica charantia extract (MCE) and lactic acid bacteria (LAB) have been considered as potential therapeutic agents against insulin resistance and hyperglycemia. In a streptozotocin-induced type 1 diabetes animal model, treatment with MCE and LAB had no effect on hyperglycemia. To evaluate the effect of MCE and LAB on insulin resistance, we chose a high-fat diet-induced insulin resistance model and co-administered MCE and Lactobacillus Acidophilus CBT-LA1, Lactiplantibacillus plantarum CBT-LP3, or Lacticaseibacillus rhamnosus CBT-LR5. MCE with CBT-LA1 or CBT-LP3 improved insulin resistance and hepatosteatosis. However, the effect of MCE and MCE with CBT-LR5 was weaker than the effect of MCE with CBT-LA1 or CBT-LP3. Momordica charantia induced insulin secretion from RIN-m5F in a dose-dependent manner. Interestingly, CBT-LA1 and CBT-LP3 enhanced the insulin secretion of MCE. These results suggest that the co-administration of MCE and a specific LAB is one approach for overcoming insulin resistance and hyperglycemia.

• The Plant Pathology Journal
• /
• v.20 no.3
• /
• pp.172-176
• /
• 2004

Bacterial isolates TRL2-3 and TRK2-2 showing anti-fungal activity in vitro test against some plant pathogens were identified as Pseudomonas putida and Micrococcus luteus, respectively. Pre-treatment with both bacterial isolates at the concentration 1.0$\times$ $10^7$ and $10^6$cfu/ml in the rhizosphere could trigger induced systemic resistance in the aerial part of cucumber plants against anthracnose caused by Colletotrichum orbiculare. However, the pre-treatment with the higher concentration at 1.0 $\times$ $10^8$ cfu/ml of both isolates could not induce resistance after challenge inoculation with C. orbiculare. As a positive control, the treatment with DL-3 amino butyric acid caused a remarkable reduction of disease severity whereas the lesions on the leaves of untreated plants developed apparently after the fungal inoculation. From these results, it was recomended that disease control using both bacterial isolates inducing systemic resistance in the field where chemical application is forbid.

• Molecules and Cells
• /
• v.43 no.7
• /
• pp.662-670
• /
• 2020

We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

• Proceedings of the KWS Conference
• /
• 2009.11a
• /
• pp.202-204
• /
• 2009

Erosion is a common failure mode of materials frequently encountered in plant and power industry. Although the erosion resistance of Fe-base alloy has been inferior to the other expensive materials, it is expected that the strain-induced martensitic transformation can impart high erosion resistance to Fe-base alloy. The key technology to develop Fe-base metal cored welding wire for erosion resistant overlay welding may include the strain-induced metallurgy for hardening rate control and the welding flux metallurgy for dilution control. Sophisticated studies showed that the strain-induced martensitic transformation behavior was related to the critical strain energy which was dependent on the alloy composition. Dilution and bead shape of overlay weld were proved to be affected by metal transfer mode during gas tungsten arc welding and elements in welding fluxes. It was considered that the highly erosion resistant Fe-base overlay weld could be achieved by precise control of alloy composition to have proper level of critical strain energy for energy absorption and welding flux formulation to have small amount of deoxidizing metallic elements for dilution.

• Korean Journal of Acupuncture
• /
• v.32 no.3
• /
• pp.116-123
• /
• 2015

Objectives : The present study was designed to investigate effects and molecular mechanisms of Atractylodes macrocephala Koidzumi extracts(AMK) on the improvement of adipocyte dysfunction induced by TNF-${\alpha}$ in 3T3-L1 adipocytes. We examined whether AMK could directly influence the inflammation and insulin resistance in 3T3-L1 adipocytes. Methods : Potential roles of AMK in the lipolysis, production of inflammatory adipokines and ROS, expression and phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein, and expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ were investigated in this study. Results : Our data demonstrated that TNF-${\alpha}$ significantly increased lipolysis, levels of MCP-1, IL-6, and ROS and phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein, while TNF-${\alpha}$ reduced the expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ in adipocytes, suggesting that TNF-${\alpha}$ induced a condition with the occurrence of inflammation and insulin resistance. Those alterations induced by TNF-${\alpha}$ were prevented by the treatment of AMK. AMK down-regulated the phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein and up-regulated the expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ on TNF-${\alpha}$-induced inflammation and insulin resistance. Conclusions : Thus, our results indicate that AMK can be used to prevent from the TNF-${\alpha}$-induced adipocyte dysfunction through MAPK, $NF{\kappa}B$ and $PPAR{\gamma}$ pathways.

• Molecules and Cells
• /
• v.38 no.12
• /
• pp.1037-1043
• /
• 2015

The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. 1 TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-$phosphoelF2{\alpha}$-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance.

• The Plant Pathology Journal
• /
• v.31 no.3
• /
• pp.305-309
• /
• 2015

After four years of cold storage, dimethachlon resistance of two laboratory-induced resistant Sclerotinia sclerotiorum isolates SCG7 and LA50 declined by 99.5% and 98.9%, respectively, and cross resistance to iprodione and procymidone also declined dramatically. Along with the decline of fungicide resistance, osmotic sensitivity to sodium chloride and glucose decreased tremendously; mycelial growth rate, sclerotia number and weight per potato dextrose agar (PDA) plate increased on average by 118.6%, 85. 5% and 64.5%, respectively; and virulence to detached leaves of oilseed rape increased by 72.7% on average. Significant negative correlations were detected between dimethachlon resistance levels and mycelial growth rate on PDA (r = -0.980, P = 0.021), and between resistance levels and lesion diameters on detached leaves of oilseed rape plants (r = -0.997, P = 0.002). These results have profound implications for assessing the potential risk for resistance development to dicarboximide fungicides in S. sclerotiorum.

• The korean journal of orthodontics
• /
• v.20 no.1
• /
• pp.47-59
• /
• 1990

Respiration is one of the most important functions which are carried out in stomatognathic system. When nasal orifice is obstructed or the resistance of upper airway is increased mouth breathing is initiated. Mouth breathing is regarded as an important etiologic factor of dentofacial anomalies. This experiment was performed to observe the influences of metabolic acidosis, tracheal resistance and vagotomy on mouth breathing. After rabbits were anesthetized with sodium pentobarbital, a pair of wire electrode was inserted into mylohyoid muscle, anterior belly of digastric muscle and dilator naris muscle to record EMG activity. Femoral vein and artery were cannulated for infusion of 0.3N HCl and collection of blood sample to determine the blood pH, and tracheal intubation was done to control airway resistance. Mouth breathing was induced by metabolic acidosis. Increase of the airway resistance through tracheal cannula intensified the activity of dilator naris, mylohyoid and digastric muscle. The higher the resistance, the larger the EMG amplitude. After bilateral vagotomy, respiratory volume and inspiatory time were increased and the activities of dilator naris, mylohyoid and digastric muscle were strengthened. It was concluded that the muscle activity related to mouth breathing was induced by metabolic acidosis and increase of tracheal tube resistance.