• Title/Summary/Keyword: M&A effect

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α, γ-Mangostins Induce Autophagy and Show Synergistic Effect with Gemcitabine in Pancreatic Cancer Cell Lines

  • Kim, Myoungjae;Chin, Young-Won;Lee, Eun Joo
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.609-617
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    • 2017
  • Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of ${\alpha}$-mangostin (${\alpha}M$) and ${\gamma}$-mangostin (${\gamma}M$) extracted from the pericarp of Garcinia mangostana L.. Both ${\alpha}$M and ${\gamma}M$ reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels. They also induced autophagy by increasing levels of microtubule-associated protein 1A/1B light chain 3B (LC3II) in both cell lines while decreasing sequestosome 1 (p62) in MIA PaCa-2. Both ${\alpha}$M and ${\gamma}M$ induced autophagy through increasing phosphorylation levels of AMP-activated protein kinase (p-AMPK) and p38-mitogen activated protein kinase (p-p38) while decreasing phosphorylation level of mammalian target of rapamycin complex 1 (p-mTOR). Of various microRNAs (miRNA), miR-18a was found to be a putative regulatory miRNA for autophagy induced by ${\alpha}$M or ${\gamma}M$. In combination with gemcitabine, a compound frequently used in pancreatic cancer treatment, ${\alpha}$M and ${\gamma}M$ showed synergistic anti-cancer effects in MIA PaCa-2. Collectively, these results suggest that ${\alpha}$M and ${\gamma}M$ can induce apoptosis and autophagy in pancreatic cancer cells and that their anti-cancer effect is likely to be associated with miR-18a. In conclusion, ${\alpha}$M and ${\gamma}M$ might be used as a potential new therapy for pancreatic cancer.

Anti-inflammatory Effect of Methanol Extract from Safflower Seeds

  • Kim, Hyun-Jin
    • International Journal of Oral Biology
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    • v.41 no.2
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    • pp.83-88
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    • 2016
  • Periodontitis is an inflammatory disease, which destroys the connective tissue and the alveolar bone. Recently, it has been suggested that the effect of natural substances could be induced into an anti-inflammatory environment. However, the effect of Safflower seed extract (SAF-M) associated with periodontitis has not been investigated yet. Therefore, the purpose of this study was to assess the anti-inflammatory effects of SAF-M. Cytotoxicity was assessed through MTS analysis using hGF and hPDL cells. Periodontitis was induced by injecting LPS into gingival tissue on the maxillary molars of rats ($45{\mu}g$ LPS/one time, 3 times a week for 3 weeks). SAF-M was administered daily at 30 mg/kg and 100 mg/kg. Alveolar bone resorption was evaluated through the micro-CT. hGF and hPDL cells showed differential cytotoxicity in response to SAF-M at 5 mg/ml and 1 mg/ml concentrations. Micro-CT showed reduction of the alveolar bone resorption in the SAF-M treatment group. These results suggested that SAF-M is a potential therapeutic agent for periodontitis.

Inhibitory Effect of Dihydroartemisinin, An Active Ingredient of Artemisia annua, on Lipid Accumulation in Differentiating 3T3-L1 Preadipocytes

  • Jang, Byeong-Churl
    • Journal of Korean Medicine for Obesity Research
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    • v.20 no.1
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    • pp.1-9
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    • 2020
  • Objectives: Artemisinin and its derivatives extracted from Artemisia annua, a Chinese herbal medicine, have variable biological effects due to structural differences. Up to date, the anti-obesity effect of dihydroartemisinin (DHA), a derivative of artemisinin, is unknown. The purpose of this study was to investigate the anti-adipogenic and lipolytic effects of DHA on 3T3-L1 preadipocytes. Methods: Oil Red O staining and AdipoRed assay were used to measure lipid accumulation and triglyceride (TG) content in 3T3-L1 cells, respectively. Cell count analysis was used to determine the cytotoxicity of 3T3-L1 cells. Western blot and real-time reverse transcription polymerase chain reaction analyses were used to analyze the expression of protein and mRNA in 3T3-L1 cells, respectively. Results: DHA at 5 μM markedly inhibited lipid accumulation and reduced TG content in differentiating 3T3-L1 cells with no cytotoxicity. Furthermore, DHA at 5 μM inhibited the expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A as well as the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) in differentiating 3T3-L1 cells. Moreover, while DHA at 5 μM had no effect on the mRNA expression of adiponectin, it strongly suppressed that of leptin in differentiating 3T3-L1 cells. However, DHA at 5 μM had no lipolytic effect on differentiated 3T3-L1 cells, as assessed by no enhancement of glycerol release. Conclusions: These results demonstrate that DHA at 5 μM has a strong anti-adipogenic effect on differentiating 3T3-L1 cells through the reduced expression and phosphorylation of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3.

Effect of long term treatment of aqueous extract of Enicostemma littorale in Type 2 diabetic patients

  • Mansuri, Mustakim M;Goyal, Bhoomika R;Upadhyay, Umesh M;Sheth, Jayesh;Goyal, Ramesh K
    • Advances in Traditional Medicine
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    • v.9 no.1
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    • pp.39-48
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    • 2009
  • We have evaluated the effect of long term treatment of Enicostemma littorale (E. littorale) in type 2 diabetic patients taking pills of aqueous extract of E. littorale regularly as a complimentary medicine for at least 9 months. The effects of E. littorale on glycemic control, lipid profile, cardiac function and DNA damage in these patients were compared with those who had not been regular in taking E. littorale but regular in taking other conventional anti-diabetics. Our data suggest that, E. littorale can maintain normal blood glucose, serum insulin, serum triglycerides levels of type 2 diabetic patients if taken regularly. E. littorale also improves insulin sensitivity, and normalize disturbed lipogram and elevated creatinine levels, thereby produces beneficial effect in preventing cardiovascular complications and may preserve the kidney function. The finding that E. littorale also prevents DNA damage suggest a long term effect in diabetic patients. E. littorale thus can be considered as safe supplementary therapy for a long term and effective management of type 2 diabetic patients.

A Numerical Study on the Stack Effect and the Neutral Plane of a Single Simplified Shaft (단일 단순수직통로의 연돌효과와 중성대에 관한 수치해석 연구)

  • Jeon, Heung-Kyun;Choi, Young-Sang;Choo, Hong-Lok
    • Fire Science and Engineering
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    • v.23 no.5
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    • pp.143-152
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    • 2009
  • The numerical analyses for each single simplified shaft with three type openings were carried out by using computational fluid dynamics model for the calculation of the pressure difference and the location of the neutral plane and the visualization of stack effect. As the height of shaft heighten, the pressure difference of stack effect is much deviated against the theoretical value. For the Type A models shorter than 30 m height of shaft and the Type B models longer than 30m, the simulation results for the location of the neutral plane are well agreed to the theoretical values with 5% less deviations just after the beginning of simulation (t = 10s). For the Type B models longer than 30m with multiple openings, therefore, it is possible to calculate the location of the neutral plane by using a CFD model. The phenomenon of the air flow of stack effect can be easily understood with the visualization of stack effect.

Involvement of spinal muscarinic and serotonergic receptors in the anti-allodynic effect of electroacupuncture in rats with oxaliplatin-induced neuropathic pain

  • Lee, Ji Hwan;Go, Donghyun;Kim, Woojin;Lee, Giseog;Bae, Hyojeong;Quan, Fu Shi;Kim, Sun Kwang
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.4
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    • pp.407-414
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    • 2016
  • This study was performed to investigate whether the spinal cholinergic and serotonergic analgesic systems mediate the relieving effect of electroacupuncture (EA) on oxaliplatin-induced neuropathic cold allodynia in rats. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water ($4^{\circ}C$) and measuring the withdrawal latency. EA stimulation (2 Hz, 0.3-ms pulse duration, 0.2~0.3 mA) at the acupoint ST36, GV3, or LI11 all showed a significant anti-allodynic effect, which was stronger at ST36. The analgesic effect of EA at ST36 was blocked by intraperitoneal injection of muscarinic acetylcholine receptor antagonist (atropine, 1 mg/kg), but not by nicotinic (mecamylamine, 2 mg/kg) receptor antagonist. Furthermore, intrathecal administration of $M_2$ (methoctramine, $10{\mu}g$) and $M_3$ (4-DAMP, $10{\mu}g$) receptor antagonist, but not $M_1$ (pirenzepine, $10{\mu}g$) receptor antagonist, blocked the effect. Also, spinal administration of $5-HT_3$ (MDL-72222, $12{\mu}g$) receptor antagonist, but not $5-HT_{1A}$ (NAN-190, $15{\mu}g$) or $5-HT_{2A}$ (ketanserin, $30{\mu}g$) receptor antagonist, prevented the anti-allodynic effect of EA. These results suggest that EA may have a significant analgesic action against oxaliplatin-induced neuropathic pain, which is mediated by spinal cholinergic ($M_2$, $M_3$) and serotonergic ($5-HT_3$) receptors.

The Characterizing Analysis of a Buried-Channel MOSFET based on the 3-D Numerical Simulation

  • Kim, Man-Ho;Kim, Jong-Soo
    • Journal of Electrical Engineering and Technology
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    • v.2 no.2
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    • pp.267-273
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    • 2007
  • A depletion-mode MOSFET has been analyzed to evaluate its electrical behavior using a novel 3-D numerical simulation package. The characterizing analysis of the BC MOSFET was performed through short-channel narrow-channel and small-geometry effects that are investigated, in detail, in terms of the threshold voltage. The DIBL effect becomes significant for a short-channel device with a channel length of $<\;3({\mu}m)$. For narrow-channel devices the variation of the threshold voltage was sharp for $<4({\mu}m)$ due to the strong narrow-channel effect. In the case of small-geometry devices, the shift of the threshold voltage was less sensitive due to the combination of the DIBL and substrate bias effects, as compared with that observed from the short-channel and narrow-channel devices. The characterizing analysis of the narrow-channel and small-geometry devices, especially with channel width of $<\;4({\mu}m)$ and channel area of $<\;4{\times}4({\mu}m^2)$ respectively, can be accurately performed only from a 3-D numerical simulation due to their sharp variations in threshold voltages.

The Effect of External Divalent Cations on Intestinal Pacemaking Activity

  • Kim, Byung-Joo;Kim, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.4
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    • pp.203-207
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    • 2005
  • Electrical rhythmicity in the gastrointestinal (GI) muscles is generated by pacemaker cells, known as interstitial cells of Cajal (ICC). In the present study, we investigated the effect of external divalent cations on pacemaking activity in cultured ICC from murine small intestine by using whole-cell patch clamp techniques. ICC generated pacemaker currents under a voltage clamp or electrical pacemaker potentials under a current clamp, and showed a mean amplitude of $-500{\pm}50$ pA or $30{\pm}1$ mV and the frequency of $18{\pm}2$ cycles/min. Treatments of the cells with external 0 mM $Ca^{2+}$ stopped pacemaking activity of ICC. In the presence of 2 mM $Ca^{2+}$, 0 mM external $Mg^{2+}$ depolarized the resting membrane potential, and there was no change in the frequency of pacemaking activity. However, 10 mM external $Mg^{2+}$ decreased the frequency of pacemaking activity ($6.75{\pm}1$ cycles/min, n=5). We replaced external 2 mM $Ca^{2+}$ with equimolar $Ba^{2+}$, $Mn^{2+}$ and $Sr^{2+}$, and they all developed inward current in the sequence of $Ba^{2+}$>$Mn^{2+}$>$Sr^{2+}$. Also the frequency of the pacemaking activity was stopped or irregulated. We investigated the effect of 10 mM $Ba^{2+}$, $Mn^{2+}$ and $Sr^{2+}$ on pacemaking activity of ICC in the presence of external 0 mM $Mg^{2+}$, and found that 10 mM $Ba^{2+}$ and $Mn^{2+}$ induced large inward current and stopped the pacemaking activity of ICC (n=5). Interestingly, 10 mM $Sr^{2+}$ induced small inward current and potentiated the amplitude of pacemaking activity of ICC (n=5). These results indicate that extracellular $Ca^{2+}$ and $Mg^{2+}$ are requisite for the pacemaking activity of ICC.

Activation of Cabbage Phospholipase D by Polyamines (폴리아민에 의한 양배추 포스포리파제 D의 활성화)

  • Eun-Hie Koh
    • Journal of the Korean Chemical Society
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    • v.47 no.5
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    • pp.466-471
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    • 2003
  • The effect of polyamines on the cabbage phospholipase D(PLD) activity was investigated. The PLD activity was determined by pH-stat titration of phosphatidic acid, one of the enzymatic reaction product, using phosphatidyl choline small unilamellar vesicles as a substrate. The cabbage PLD was activated approximately 4 fold by spermine at 1 mM concentration. This spermine effect appears to be similar to the previous report on the PLD activation of rat brain mitochondrial fraction. It was also found that cationic polypetides such as polylysine and polyhistidine exerted a marked enhancement effect on the cabbage PLD. Particularly polyhistidine exerted approximately 5.5 fold enhancement effect at 0.062 mM concentration. The polyamine effect on the cabbage PLD was reexamined in the phosphatidylcholine/sodium dodecyl sulfate mixed micellar system. The relevance of polyamine effect on PLD activity is discussed in relation to the active site of PLD.