• The Korean Journal of Physiology and Pharmacology
• /
• 제21권4호
• /
• pp.361-370
• /
• 2017

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

• 동의신경정신과학회지
• /
• 제34권4호
• /
• pp.349-358
• /
• 2023

Objectives: We used the 2019 Korea Health Panel Annual Data to analyze factors related to visits to Korean medicine (KM) outpatient clinics among patients with mood disorders in Korea. Methods: Individuals aged 19 years or older, with depressive or bipolar disorders, and with a record of using Western medicine (WM) and/or the KM medical service were included. The 266 subjects were classified into the WM group or the integrative medicine (IM) group. The Andersen healthcare utilization model was used to analyze factors that potentially influenced the subjects' healthcare utilization. Binomial logistic regression analysis was used to analyze factors influencing the use of IM medical services. Results: Among the subjects, 75.56% (n=201) were in the WM group, and 24.44% (n=65) were in the IM group. Statistically significant differences were observed in residential areas, total annual income, the presence of disability, and the level of pain/discomfort between the two groups. Regression analysis found that residential areas and pain/discomfort were factors related to the use of IM services. Specifically, reporting "a lot" of pain/discomfort compared to "no" pain/discomfort showed a significant positive relationship with the use of IM (odds ratio=4.57, 95% confidence interval=1.79 to 11.70). Conclusions: This study was the first to analyze the status of KM medical service use and related factors among patients with mood disorders in Korea. The finding that the presence of pain/discomfort was positively correlated with the use of KM services is potentially related to medically unexplained physical symptoms or somatization phenomena.

• 대한통합의학회지
• /
• 제12권1호
• /
• pp.63-71
• /
• 2024

Purpose : Skin is the primary barrier to protect the body from various exogenous factors. Among them, UVB exposure can cause the induction of not only excessive inflammatory responses but also the degradation of extracellular matrix (ECM), including collagen and elastin. This study tried to investigate the ameliorative effect of Persicaria perfoliata ethanol extract (PPEE) on UVB-irradiated photodamage through the regulation of activator protein (AP)-1, phosphoinositide 3-kinase (PI3K)/Akt, and mitogen-activated protein kinase (MAPK) signaling molecules in HaCaT cells. Methods : The cytotoxicity of PPEE on HaCaT cells was evaluated by the WST-1 assay. The 80 mJ/cm² of UVB (312 nm) was irradiated on HaCaT cells to induce the photodamage. Western blot analysis was conducted to investigate the protein expression levels of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9, and heme oxygenase (HO)-1 for ameliorative status by PPEE treatment in UVB-exposed HaCaT cells. In addition, the activated status of the inflammatory transcription factor, AP-1, as well as upstream signaling molecules, PI3K/Akt, and MAPK, were also evaluated by Western blot analysis. Results : Any cytotoxic effect was not induced at the concentration up to 200 ㎍/ml by PPEE treatment. Protein expression levels of COX-2 and MMP-9 were significantly down- and up-regulated by PPEE treatment. The inflammatory transcription factor AP-1, stimulated by UVB irradiation, was also significantly attenuated by PPEE treatment. The phosphorylated status of PI3K/Akt and MAPK were mitigated by PPEE treatment in UVB-exposed HaCaT cells. Moreover, PPEE treatment potently accelerated the expression of HO-1 and its transcription factor, nuclear factor-erythroid 2-related factor (Nrf)2, which is known for its anti-inflammatory activity. Conclusion : Consequently, PPEE treatment significantly regulated COX-2 and MMP-9 expressions in UVB-irradiated HaCaT cells. The inflammatory transcription factor AP-1, along with upstream signaling molecules PI3K/Akt and MAPKs, were also attenuated by PPEE treatment in UVB-exposed HaCaT cells. Additionally, PPEE treatment exaggerated HO-1 expression and Nrf2 activation, which might have contributed to the anti-inflammatory activity of PPEE. These results indicate that PPEE could be a candidate for attenuating UVB-induced photodamage in human skin.

• Biomolecules & Therapeutics
• /
• 제18권1호
• /
• pp.56-64
• /
• 2010

Pentoxifylline (PTX) has been used for the local reduction of fat tissue in the clinical setting. However, its safety and efficacy have not been proven. The aim of this study was to evaluate the effects of PTX on cell lines established from fat tissue. Newly cultured human preadipocytes and adipocytes from subcutaneous abdominal fat in addition to purchased human lung fibroblasts and keratinocytes were treated with PTX at different concentrations. Cell viability was determined using the Cell counting kit (CCK)-8 assay and lipolysis was evaluated using an Elisa kit. DNA fragmentation, Western blot analysis, Hoechst and Propidium Iodide (PI) staining and fluorescence activated cell scanning analysis were performed to confirm apoptosis. The viability of adipocytes, preadipocytes, keratinocytes and fibroblasts was markedly decreased at concentrations of PTX above 20 mM. Apoptosis was induced at concentrations of PTX over 40 mM in all cell lines. Lipolysis was increased by 60% at concentrations of PTX of 20 mM compared to the control. In conclusion, the results of this study showed that 20 mM of PTX induced lipolysis. At concentrations over 20 mM, PTX reduced the viability of all cells studied including: adipocytes, preadipocytes, fibroblasts and keratinocytes, in a non-specific manner.

• Journal of Ginseng Research
• /
• 제47권2호
• /
• pp.237-245
• /
• 2023

Background: Ginsenoside Rg2 (Rg2) has a variety of pharmacological activities and provides benefits during inflammation, cancer, and other diseases. However, there are no reports about the relationship between Rg2 and atherosclerosis. Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to detect the cell viability of Rg2 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). The expression of inflammatory factors in HUVECs and the expression of phenotypic transformation-related marker in VSMCs were detected at mRNA levels. Western blot method was used to detect the expression of inflammation pathways and the expression of phenotypic transformation at the protein levels. The rat carotid balloon injury model was performed to explore the effect of Rg2 on inflammation and phenotypic transformation in vivo. Results: Rg2 decreased the expression of inflammatory factors induced by lipopolysaccharide in HUVECs-without affecting cell viability. These events depend on the blocking regulation of NF-κB and p-ERK signaling pathway. In VSMCs, Rg2 can inhibit the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet derived growth factor-BB (PDGF-BB)-which may contribute to its anti-atherosclerotic role. In rats with carotid balloon injury, Rg2 can reduce intimal proliferation after injury, regulate the inflammatory pathway to reduce inflammatory response, and also suppress the phenotypic transformation of VSMCs. Conclusion: These results suggest that Rg2 can exert its anti-atherosclerotic effect at the cellular level and animal level, which provides a more sufficient basis for ginseng as a functional dietary regulator.

• Journal of Microbiology and Biotechnology
• /
• 제33권3호
• /
• pp.398-409
• /
• 2023

LncRNAs play crucial roles in the progression of colon adenocarcinoma (COAD), but the role of LINC01232 in COAD has not received much attention. The present study was designed to explore the related mechanisms of LINC01232 in the progression of COAD. LINC01232, miR-181a-5p, p53, c-myc, Bcl-2, cyclin D1, p16, Bax, VEGF, E-cadherin, vimentin, N-cadherin and SDAD1 expressions were determined by western blot and qRT-PCR. CCK-8, tubule formation, and Transwell assays were employed to detect proliferation, angiogenesis, and migration/invasion of COAD cells, respectively. The relationship between LINC01232 and miR-181a-5p was predicted by LncBase Predicted v.2, and then verified through dual luciferase reporter gene assay. According to the results, LINC01232 was highly expressed in COAD cells and enhanced proliferation, angiogenesis, migration, and invasion of COAD cells. Downregulated LINC01232 promoted expression of p53 and p16, and inhibited c-myc, Bcl-2 and cyclin D1 expressions in COAD cells, while upregulation of LINC01232 generated the opposite effects. LINC01232 was negatively correlated with miR-181a-5p while downregulated miR181a-5p could reverse the effects of siLINC01232 on cell proliferation, angiogenesis, migration, and invasion. Similarly, miR-181a-5p mimic could also offset the effect of LINC01232 overexpression. SiLINC01232 increased the expressions of Bax and E-cadherin, and decreased the expressions of VEGF, vimentin, N-cadherin and SDAD1, which were partially attenuated by miR-181a-5p inhibitor. Collectively, LINC01232 enhances the proliferation, migration, invasion, and angiogenesis of COAD cells by decreasing miR-181a-5p expression.

• Animal cells and systems
• /
• 제8권1호
• /
• pp.49-55
• /
• 2004

In vertebrates, multisubunit cofactors regulate gene expression through interacting with cell-type- and gene-specific DNA-binding proteins in a chromatin-selective manner. ADD1/SREBP1c regulates fatty acid metabolism and insulin-dependent gene expression through binding to SRE and E-box motif with dual DNA binding specificity. Although its transcriptional and post-translational regulation has been extensively studied, its regulation by interacting proteins is not well understood. To identify cellular proteins that associate with nuclear form of ADD1/SEBP1c, we employed the GST pull-down system with Hela cell nuclei extract. In this study, we demonstrated that Ku proteins interact specifically with ADD1/SREP1c protein. GST pull-down combined with peptide sequencing analysis revealed that Ku80 binds to ADD1/SREBP1c in vitro. Additionally, western blot analysis showed that Ku70, a heterodimerizing partner of Ku80, also associates with ADD1/SREBP1c. Furthermore, co-transfection of Ku70/Ku80 with ADD1/SREBP1c enhanced the transcriptional activity of ADD1/SREBP1c. Taken together, these results suggest that the Ku proteins might be involved in the lipogenic and/or adipogenic gene expression through interacting with ADD1/SREBP1c.

• 대한통합의학회지
• /
• 제11권4호
• /
• pp.73-82
• /
• 2023

Purpose : Cymbopogon citratus, also known as lemongrass, has widely spread around the world and its essential oil is usually applied in food, perfume, and other industrial purposes. In addition, C. citratus has also been used for the treatment of inflammation, digestive disorders, and diabetes in traditional medicine. In this study, the antioxidative activity of C. citratus ethanol extract (CCEE) was analyzed in RAW 264.7 cells through the induction of one of phase II enzymes, heme oxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor (Nrf)2, mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)/Akt. Methods : The antioxidative activity of CCEE against oxidative stress and its underlying molecular mechanisms were analyzed by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results : The results exhibited that CCEE potently attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS levels in a dose-dependent manner without any cytotoxicity. CCEE treatment significantly induced the expression of HO-1 which is known for its antioxidative capacity. In addition, CCEE treatment significantly upregulated the expression of Nrf2, a corresponding transcription factor for the regulation of antioxidative enzymes, which was in accordance with the HO-1 overexpression. MAPK and PI3K/Akt were also evaluated for their important roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, the potent HO-1 expression was mediated by not extracellular regulated kinase (ERK), c-Jun NH2 terminal kinase (JNK), p38, but phosphoinositide 3-kinase (PI3K) phosphorylation. To confirm the antioxidative activity of CCEE-induced HO-1 expression, oxidative damage was initiated by t-BHP and attenuated by CCEE treatment, which was identified by HO-1 selective inhibitor and inducer. Conclusion : Consequently, CCEE potently induced the HO-1-mediated antioxidative potential through the modulation of Nrf2 and PI3K/Akt signaling pathways in RAW 264.7 cells. These results suggest that CCEE could be a promising strategy for the mitigation against cellular oxidative damage.

• Physical Therapy Rehabilitation Science
• /
• 제8권1호
• /
• pp.22-31
• /
• 2019

Objective: For knee osteoarthritis (OA), there is a demand for alternative modalities in order to delay surgery and to avoid the side effects of medications. This study compared the effects of applying seaweed pack and mudpack for the treatment of knee OA. Design: Randomized controlled trial. Methods: Twenty-five patients with knee OA who satisfied the criteria were included. The patients were divided into two groups according to the treatment method: mudpack (n=12) and seaweed pack (n=13). The two groups were treated for 20 minutes, twice a day for five continuous days at the Ocean Healing Center at Wando Island, South Korea. Participants were assessed by clinical scores (Western Ontario and McMaster Universities Osteoarthritis Index, Hospital for Special Surgery Knee Score, Knee injury and Osteoarthritis Outcome Score and 36-Item Short Form Health Survey) and lab results (erythrocyte sedimentation rate, C-reactive protein, insulin-like growth factor-1 [IGF-1], tumor necrosis $factor-{\alpha}$ [$TNF-{\alpha}$]) during the follow-up period. Results: For the most part, clinical scores improved after therapy and maintained improvements for four weeks in both groups (p<0.05). In the seaweed group, $TNF-{\alpha}$ was significantly decreased at two weeks post-therapy (p<0.05). In both groups, IGF-1 was significantly increased immediately post-therapy (p<0.05). There were no statistically significant differences after therapy between the groups in clinical scores and labs. Conclusions: Seaweed packs and mudpacks had similar positive effects for knee OA. Additionally, the seaweed pack group showed decreased levels of $TNF-{\alpha}$ at two weeks post-treatment, which may explain the reduced inflammatory reaction. For rehabilitation therapy, use of seaweed packs may serve as an alternative modality for the treatment of knee OA.

• Journal of Veterinary Science
• /
• 제24권3호
• /
• pp.23.1-23.16
• /
• 2023

Background: Irritable bowel syndrome (IBS) is a functional bowel disorder (FBD). Objectives: To assess the therapeutic effects of paeoniflorin (PF) on IBS in rats. Method: Sixty male Sprague-Dawley rats were randomly divided into normal, model, positive drug, low-dose PF, medium-dose PF and high-dose PF groups (n = 10). After gavage for 2 consecutive weeks, the effect of PF on abdominal pain symptoms was assessed based on the abdominal withdrawal reflex (AWR) score, fecal water content and pathological changes in colon tissues. D-lactate, interleukin-1β (IL-1β), transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay, and phosphorylated nuclear factor kappa B (p-NF-κB) p65 was detected by Western blotting. The abundance and diversity changes of intestinal flora were explored using 16S ribosomal RNA sequencing. Result: In PF groups, the mucosal morphology of colon tissues was intact, and the glands were arranged neatly and structured clearly, without obvious inflammatory cell infiltration. Compared with the model group, PF groups had significantly elevated pain threshold, and mRNA and protein levels of zonula occludens-1 (ZO-1) and occludin, decreased AWR score at 20 mmHg pressure, fecal water content, mRNA levels of IL-1β, TGF-β, and TNF-α, protein level of p-NF-κB p65 and level of serum D-lactate, and reduced levels of serum IL-1β, TGF-β, and TNF-α (p < 0.05, p < 0.01). PF groups had higher abundance of Lactobacillus, Akkermansia, Alistipes, and Bacteroides, but lower abundance of Desulfovibrio, Parasutterella, and Enterococcus than those of the model group. Conclusions: PF exerts therapeutic effects on IBS in rats probably by regulating the intestinal flora, and then up-regulating the expressions of ZO-1 and occludin in colon tissue while down-regulating the levels of IL-1β, TGF-β, TNF-α, D-lactate and p-NF-κB p65.