• Journal of Pharmacopuncture
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• v.22 no.3
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• pp.160-165
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• 2019

Objectives: The aim of this study was to evaluate the effect of Ribes khorasanicum (R. khorasanicum); a plant growing in north Khorasan of Iran; on cardiovascular and stress oxidative in acute hypertension induced by N-nitro-l-arginine methyl ester (L-NAME), anitric oxide synthase inhibitor. Methods: Rats were divided into Control, L-NAME (10 mg/kg), Sodium Nitroprusside (SNP) (50 mg/kg) + L-NAME and three treated groups with R. khorasanicum (4, 12 and 24 mg/kg) groups + L-NAME. L-NAME and SNP were injected intravenously and extract intraperitoneal. In R. khorasanicum groups, L-NAME was injected 30 min after injection of the extract. Systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were recorded continuously using power lab software. At the end of study oxidative stress parameters including of total thiol content (SH), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in heart and aorta of all groups were also measured. Results: In groups 4 and 24 mg/kg extract +L-NAME, there was a non-significant decrease in SBP and MAP compared to L-NAME group but dose 12 mg/kg significantly attenuate the effect of L-NAME(P < 0.05). In L-NAME group the heart and aorta tissues antioxidant enzymes levels decreased, while in treated rats these enzymes significantly increased. Conclusion: The extract of R. khorasanicum in dose 12 mg/kg show anti-hypertensive effect that is mediated by an effect on NO system or antioxidant parameters.

• Journal of Ginseng Research
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• v.43 no.3
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• pp.394-401
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• 2019

Background: Ginsenoside Rb1, a triterpene saponin, is derived from the Panax ginseng root and has potent antiinflammatory activity. In this study, we determined if Rb1 can increase macrophage phagocytosis and elucidated the underlying mechanisms. Methods: To measure macrophage phagocytosis, mouse peritoneal macrophages or RAW 264.7 cells were cultured with fluorescein isothiocyanate-conjugated Escherichia coli, and the phagocytic index was determined by flow cytometry. Western blot analyses were performed. Results: Ginsenoside Rb1 increased macrophage phagocytosis and phosphorylation of p38 mitogenactivated protein kinase (MAPK), but inhibition of p38 MAPK activity with SB203580 decreased the phagocytic ability of macrophages. Rb1 also increased Akt phosphorylation, which was suppressed by LY294002, a phosphoinositide 3-kinase inhibitor. Rb1-induced Akt phosphorylation was inhibited by SB203580, (5Z)-7-oxozeaenol, and small-interfering RNA (siRNA)-mediated knockdown of $p38{\alpha}$ MAPK in macrophages. However, Rb1-induced p38 MAPK phosphorylation was not blocked by LY294002 or siRNA-mediated knockdown of Akt. The inhibition of Akt activation with siRNA or LY294002 also inhibited the Rb1-induced increase in phagocytosis. Rb1 increased macrophage phagocytosis of IgG-opsonized beads but not unopsonized beads. The phosphorylation of p21 activated kinase 1/2 and actin polymerization induced by IgG-opsonized beads and Rb1 were inhibited by SB203580 and LY294002. Intraperitoneal injection of Rb1 increased phosphorylation of p38 MAPK and Akt and the phagocytosis of bacteria in bronchoalveolar cells. Conclusion: These results suggest that ginsenoside Rb1 enhances the phagocytic capacity of macrophages for bacteria via activation of the p38/Akt pathway. Rb1 may be a useful pharmacological adjuvant for the treatment of bacterial infections in clinically relevant conditions.

• Journal of the Korean Society of Mineral and Energy Resources Engineers
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• v.55 no.6
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• pp.670-687
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• 2018

This paper reviews the structures, physical and chemical properties, origins and global distribution, amount of energy resources, production technologies, and environmental impacts of gas hydrates to understand the gas hydrates as future energy sources. Hydrate structures should be studied to clarify the fundamentals of natural gas hydrates, hydrate distributions, and amount of energy sources in hydrates. Phase equilibria, dissociation enthalpy, thermal conductivity, specific heat, thermal diffusivity, and fluid permeability of gas hydrate systems are important parameters for the the efficient recovery of natural gas from hydrate reservoirs. Depressurization, thermal stimulation, inhibitor injection, and chemical exchange methods can be considered as future technologies to recover the energy sources from natural gas hydrates, but so far depressurization is the only method to have been applied in test productions of both onshore and offshore hydrates. Finally, we discuss the hypotheses of environmental impacts of gas hydrates and their contribution to global warming due to hydrate dissociation.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.175-183
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• 2021

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

• Advances in nano research
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• v.12 no.3
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• pp.301-317
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• 2022

Many studies have shown that Mg-Nd-Zn-Zr (abbreviated as JDBM) alloy has good biocompatibility and biodegradability as well as promotion of cell adhesion, proliferation and differentiation, and Wnt/β-catenin signaling pathway may play a unique role in joint tissue by controlling the function of chondrocytes, osteoblasts and synoviocytes. However, it is not clear whether the JDBM alloy induces osteochondral repair through Wnt/β-catenin signaling pathway. This study aims to verify that JDBM alloy can repair osteochondral defects in rats, which is realized by Wnt/β-catenin signaling pathway. In this study, the osteochondral defect model of the right femoral condyle non-weight-bearing area in rats was established and randomly divided into three groups: Control group, JDBM alloy implantation group and JDBM alloy implantation combined with signaling pathway inhibitor drug ICRT3 injection. It was found that after JDBM alloy implantation, the bone volume fraction (BVF) became larger, the bone trabeculae were increased, the relative expression of osteogenesis gene Runx2, Bmp2, Opn, Ocn and chondrogenesis gene Collagen II, Aggrecan were increased, and the tissue repair was obvious by HE and Masson staining, which could be inhibited by ICRT3.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.239-252
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• 2024

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ㎍/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ㎍/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

• Journal of Life Science
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• v.21 no.11
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• pp.1607-1611
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• 2011

To analyze the role of Bombyx mori transferrin (BmTf) in response to microbes or oxidative stress, we investigated the level of BmTf transcripts in B. mori treated with various microbes and oxidative stress inducers. BmTf mRNA was mainly expressed in the epidermis and fat in the bodies of B. mori injected with Escherichia coli, and up regulated in response to microbes such as bacteria, fungi, or viruses, but was hardly altered in response to oxidative stress inducers such as $H_2O_2$, Cu, or $FeCl_3$. We also confirmed that BmTf mRNA expression was increased in Bm5 cells treated with ERK, PLC, PKA, PI3K, MAPK, or JNK inhibitors, respectively. To identify the major inducer of BmTf expression, we analyzed the amount of serum iron in the hemolymph of B. mori after injection or feeding with E. coli or $FeCl_3$. The results showed that the amount of serum iron was not changed by injection and feeding with E. coli, although BmTf mRNA was increased by injection with E. coli. On the contrary, injection and feeding with $FeCl_3$ significantly increased the amount of serum iron, although they did not alter the BmTf mRNA level. On the basis of these results, we assume that up-regulation of BmTf in B. mori is closely related to the defense of microorganism, and BmTf may be expressed at the basal constitutive level when it plays a role in iron metabolism by maintaining iron homeostasis and in the insect defense mechanism against oxidative stress.

• Clinics in Shoulder and Elbow
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• v.15 no.1
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• pp.1-7
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• 2012

Purpose: The purpose of this study was to identify the effectiveness of multimodal pain control method in an early phase after arthroscopic rotator cuff repair, under interscalene brachial plexus block, this study was performed. Materials and Methods: The study was progressed with the 80 cases of arthroscopic rotator cuff repair. Interscalene brachial plexus block was used to all of the 80 cases and patients were divided into 2 groups. Group A consisted of patients injected with bupivacaine, through subacromial space catheter after surgery, and group B consisted of patients with additional method of multimodal pain control using oral opioids, acetaminophen-tramadol complex and selective COX2 inhibitor. Subacromial cathter was removed after injection in both groups. The pain during the day time and night time was compared on the operation day, postoperative 1st, 2nd, 3rd day and 2nd weeks, and it was measured with VAS (visual analogue scale) score. Additionally, the number of ketolorac injection and side-effect related to analgesics was compared between the 2 groups. Results : The mean VAS score of night time on the operation day and day/night time pain of the 1st, 2nd, 3rd day and 2nd weeks was 7.4, 7.0/6.8, 4.5/5.2, 4.8/5.0, 2.2/2.7 on group A and 6.5, 4.3/5.4, 3.2/4.3, 3.0/4.1, 2.4/2.5 on group B, respectively. Significant difference was observed in the night pain on the operation day, 1st, 2nd, 3rd day time and 1st night time pain (p<.05). The average number of ketololac injection was 1.1 and 0.5 in each group, and there was no difference in the frequency of side effects. Conclusion: Multimodal pain control method, after arthroscopic rotator cuff repair, showed an effective early pain control and improved patients' satisfaction.

• Journal of Life Science
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• v.26 no.5
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• pp.531-536
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• 2016

We previously showed that NAD(P)H:quinone oxidoreductase 1 (NQO1) knockout (KO) mice exhibited spontaneous inflammation with markedly increased mucosal permeability in the gut, and that NQO1 is functionally associated with regulating tight junctions in the mucosal epithelial cells that govern the mucosal barrier. Here, we confirm the role of NQO1 in the formation of tight junctions by human colonic epithelial cells (HT29). We treated HT29 cells with a chemical inhibitor of NQO1 (dicumarol; 10 μM), and examined the effect on the transepithelial resistance of epithelial cells and the protein expression levels of ZO1 and occludin (two known regulators of tight junctions between gut epithelial cells). The dicumarol-induced inhibition of NQO1 markedly reduced transepithelial resistance (a measure of tight junctions) and decreased the levels of the tested tight junction proteins. In vivo, luminal injection of dicumarol significantly increased mucosal permeability and decreased ZO1 and occludin protein expression levels in mouse guts. However, in contrast to the previous report that the epithelial cells of NQO1 KO mice showed marked down-regulations of the transcripts encoding ZO1 and occludin, these transcript levels were not affected in dicumarol-treated HT29 cells. This result suggests that the NQO1-depedent regulation of tight junction molecules may involve multiple processes, including both transcriptional regulation and protein degradation processes such as those governed by the ubiquitination/proteasomal, and/or lysosomal systems.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.193-201
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• 1999

This study was designed to evaluate the effects of opioid receptor agonists on the spontaneous alternation behaviour in an animal model of obsessivecompulsive disorder in rats. According to the theory that dopamine is related to the biological etiology of obsessive-compulsive disorder, the effect of the nalbuphine(opioid kappa agonist) and the tramadol(opioid mu agonist), which act as manipulating agents on the inhibition or stimulation of dopamine release, in the spontaneous alternation behaviour were evaluated. 24 hours prior to the experiment, rats were food-deprived. These rats were put into the T-maze, in which white and black goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for each time. After identifying the stable baseline of spontaneous alternation behaviour, nonselective 5-HT agonist 5-MeODMT(1.25mg/kg/IP) disrupted spontaneous alternation. Rats were stratified into fluoxetine(10mg/kg/IP), nalbuphine(10mg/kg/IP), tramadol(46.4mg/kg/IP), and saline(0.5cc/IP) injection group with experimental drug treatment for 21 days. The effects on the 5-MeODMT(1.25mg/kg/IP) induced disruption of spontaneous alternation behaviour were checked at the next day of discontinuation of drug treatment. The results were as follows ; 1) At the day after 21 days of the drug treatment, the nalbuphine treated group and the fluoxetine treated group showed significant difference from the tramadol treated group and the saline treated group in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. 2) Within each drug treatment group, the fluoxetine treated group showed significant difference between before and after the treatment of fluoxetine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. And also, the nalbuphine treated group showed significant difference between before and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. There was no difference between the baseline and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. We indentified that the opioid kappa agonist that act as dopamine release inhibitor affect the spontaneous alternation behaviour which is an animal model of obsessive-compulsive disorder in rat.