• BMB Reports
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• v.55 no.11
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• pp.547-552
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• 2022

Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib.

• The Korea Journal of Herbology
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• v.29 no.3
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• pp.51-58
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• 2014

Objectives : In order to investigate the efficacy of BJBB on atopic dermatitis, various anti-inflammatory factors were studied. Methods : In-vitro, inflammatory mediators, such as MTT and nitric oxide were detected after the addition of LPS with or without BJBB in Raw 264.7 cells. In-vivo, in order to verify the effectiveness of BJBB in atopic dermatitis animal model, its role in inflammation factors and histological changes were observed in NC/Nga mice. Results : BJBB showed cell viability of 100% or higher in all concentration in Raw 264.7 cells. BJBB inhibited LPS-induced productions of inflammatory mediators nitric oxide in RAW 264.7cells. BJBB treated group showed significant decrease in the expression of IL-1b, IL-6 and TNF-a by 40%, 80% and 44% respectively. Also the group showed decrease in the transcription of IL-1b, IL-6 and TNF-a mRNA in spleen by 41%, 93% and 39% respectively. BJBB treated group showed significant decrease in WBC, neutrophil, lympocyte and monocytes immune cell ratio in blood by 54%, 63%, 57% and 86% respectively. BJBB treated group showed decrease in the expression of IgG by 39% respectively. Also, infiltration of adipocytes into skin was suppressed and the thickness of epidermis and dermis were relatively decreased in the BJBB treated group. Conclusion : BJBB has an anti-inflammatory effects in NC/Nga mouse. Thus, these results suggested a beneficial effect of BJBB in treatment with Atopic dermatitis and inflammatory.

• The Korea Journal of Herbology
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• v.33 no.5
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• pp.67-72
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• 2018

Objectives : Natural extracts have been extensively studied to replace single agent drugs that cause a variety of side effects. However, studies of changes to the formulation of natural extracts has not been nearly proceed. We aimed to investigate whether pharmacological stability of hyeonggaeyeongyotang gagambang (HYT) is altered by formulation changes for foaming tablet. Methods : In this study, we performed freeze - drying of HYT, which is known to have antioxidant and anti - inflammatory properties, and then changed the formulation by foaming. Results : As a result, the foaming reaction appeared normally when HYT foamed tablets were put into water, and almost all of the substances were dissolved in the aqueous solution. In addition, we confirmed using high-performance liquid chromatograph that the geniposide used as an indicator material of HYT was stable in most of the formulations. It was confirmed that the change of HYT formulation did not affect the antioxidant efficacy by the 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid assay. Moreover, quantitative real-time PCR confirmed that the inhibitory effect of HYT on IL-$1{\beta}$ mRNA expression induced by lipopolysaccharides treatment in murine macrophage RAW 264.7 cells was similar in the solution of foaming tablet. Conclusions : These results suggest that the materials with various pharmacological effects can be stably maintained even when the formulation is changed by the foaming action of HYT. Our results are expected to provide important basic knowledge on formulation changes using various natural extracts.

• The Korea Journal of Herbology
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• v.32 no.6
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• pp.55-62
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• 2017

Objectives : This study aims to evaluate the effects of natural herb mixutre (NHM) on atopic dermatitis and skin regeneration using in vivo test. Methods : NHM was prepared with DW. 25% of NHM was applied to skin lesion, where atopic dermatitis was induced by DNCB in NC/Nga mice. The levels of cytokines (IL-4, IL-5, IL-6, IL-13, TNF-a, and $IFN-{\gamma}$), and IgE in serum were measured by Luminex. Immune cells (WBC, eosinophil, lymphocyte, and monocyte) in blood were counted by coulter counter. The gross investigation of atopic dermatitis index score test were performed during the NHM treatment period. Also, the histopathological change of dorsal skin was observed by H&E and M&T staining. Results : NHM showed the levels of IL-4, IL-5, IL-6, IL-13, IgE, WBC, eosinophil, lymphocyte, and monocyte in serum or blood were significantly decreased. On the contrary, the productions of FGF, and VEGF were increased in the serum. Also, atopic dermatitis index score in NHM-treated mice were observed in the similar levels to those of normal group. Histological examination demonstrated that NHM suppressed immune cell infiltration and thickening of epidermis, meanwhile the extraction induced collagen production in the dorsal skin. Conclusion : This study demonstrated that NHM is appeared to be effective on atopic dermatitis and skin regeneration efficacy based on the observations with hematologic, gross, and histologic examinations. Therefore, we suggest that NHM could be effectively used as an external therapeutics against atopic dermatitis and a consequence skin damage.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.95-106
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• 2013

Objectives : The researcher investigated the anti-obesity effect of Alismatis Orientale Rhizoma(AP) water extract in mice fed a high fat diet and focused on the analysis of local area adipose tissue. Methods : Male ICR mice were divided into three groups, which were fed either a normal AIN diet, a 45% high fat diet (CT group), or a high fat diet and orally administration with a concentrations of 100 mg/kg (AP100 group) and 300 mg/kg body weight (AP300 group) for eight weeks. Results : As compared with CT group, AP100 group showed significant reductions in absolute weight of liver. As compared with CT group, AP100 group and AP300 group showed significant reductions in weight gain and relative weight of total fat. AST, triglyceride, total-cholesterol levels from the AP 100 group and 300 group were significantly lower than those of the CT, and ALT, LDL-cholesterol levels from the AP 100 group was significantly lower than those of the CT. But serum HDL-cholesterol levels from the AP 100 group and 300 group were significantly higher than those of the CT. And serum adiponectin levels from the AP 100 group was significantly higher than those of the CT. In result of real time PCR, all mRNA expression(PEPCK, G6Pase, PGC-$1{\alpha}$ and $ERR{\gamma}$) of two experimental groups were significantly decreased compared to those of CT group. The treatment with AP on local abdominal area made a fat cell size lessen on the fat tissue in the abdominal cavity and subcutaneous area. Conclusions : These results suggest that AP has an anti-obesity effect and the effect is mediated by inhibition of fat gain.

• Nutrition Research and Practice
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• v.16 no.4
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• pp.435-449
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• 2022

BACKGROUND/OBJECTIVES: Cheonggukjang is a traditional fermented soybean paste with significant health-promoting effects. On the other hand, there have been insufficient studies on the safety and efficacy of Cheonggukjang, which is produced using traditional methods containing toxins and biogenic amines (BAs). This study compared the laxative effect of Cheonggukjang, containing high or low levels of toxins and BAs (HTBC or LTBC) in a loperamide (Lop)-induced constipation mouse model. MATERIALS/METHODS: To induce constipation, Lop (5 mg/kg) was administered orally to ICR mice twice a day for 4 days, and the dose was increased to 8 mg/kg after a 3-day rest period. Cheonggukjang (500 mg/kg, HTBC, or LTBC respectively) was administered for four weeks before the Lop treatment. RESULTS: The number of stools, fecal weight, water contents, gastrointestinal transit, and histological alterations were recovered significantly in the HTBC or LTBC groups. HTBC and LTBC administration did not induce significant changes in body weight, dietary intake, and behavior. The opioid-receptor downstream signaling pathway in colon tissues was also evaluated. The c-Kit, stem cell kinase, and mitogen-activated protein kinases subfamilies, including extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinases, and p38, were all downregulated in the HTBC or LTBC-administered mice colon compared to the Lop group. CONCLUSION: These results show that Cheonggukjang, containing high levels of toxins and BAs, have a similar laxative effect in a mouse model of Lop-induced constipation.

• Journal of Veterinary Science
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• v.23 no.3
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• pp.48.1-48.12
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• 2022

Background: The poor intracellular concentration of enrofloxacin might lead to treatment failure of cow mastitis caused by Staphylococcus aureus small colony variants (SASCVs). Objectives: In this study, enrofloxacin composite nanogels were developed to increase the intracellular therapeutic drug concentrations and enhance the efficacy of enrofloxacin against cow mastitis caused by intracellular SASCVs. Methods: Enrofloxacin composite nanogels were formulated by an electrostatic interaction between gelatin (positive charge) and sodium alginate (SA; negative charge) with the help of CaCl₂ (ionic crosslinkers) and optimized by a single factor test using the particle diameter, zeta potential (ZP), polydispersity index (PDI), loading capacity (LC), and encapsulation efficiency (EE) as indexes. The formation mechanism, structural characteristics, bioadhesion ability, cellular uptake, and the antibacterial activity of the enrofloxacin composite nanogels against intracellular SASCVs strain were studied systematically. Results: The optimized formulation was comprised of 10 mg/mL (gelatin), 5 mg/mL (SA), and 0.25 mg/mL (CaCl₂). The size, LC, EE, PDI, and ZP of the optimized enrofloxacin composite nanogels were 323.2 ± 4.3 nm, 15.4% ± 0.2%, 69.6% ± 1.3%, 0.11 ± 0.02, and -34.4 ± 0.8 mV, respectively. Transmission electron microscopy showed that the enrofloxacin composite nanogels were spherical with a smooth surface and good particle size distributions. In addition, the enrofloxacin composite nanogels could enhance the bioadhesion capacity of enrofloxacin for the SASCVs strain by adhesive studies. The minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibitory concentration, and minimum biofilm eradication concentration were 2, 4, 4, and 8 ㎍/mL, respectively. The killing rate curve had a concentration-dependent bactericidal effect as increasing drug concentrations induced swifter and more radical killing effects. Conclusions: This study provides a good tendency for developing enrofloxacin composite nanogels for treating cow mastitis caused by intracellular SASCVs and other intracellular bacterial infections.

• Clinical Pain
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• v.19 no.1
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• pp.8-15
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• 2020

Objective: To compare the therapeutic efficacy of the bone marrow aspirate concentrate (BMAC)- platelet-rich plasma (PRP) complex with hyaluronic acid in patients with knee osteoarthritis. Method: Thirty-four patients with knee osteoarthritis participated in this study. Seventeen patients in the study group underwent BMAC and PRP extraction followed by intra-articular injection of BMAC-PRP complex within affected knee. Seventeen patients in the control group underwent intra-articular injection of hyaluronic acid. Knee injury, osteoarthritic outcome score (KOOS), and EuroQol-5D (EQ-5D) questionnaire were evaluated before, one month, three months, and six months after the injection. Results: There were statistically significant temporal differences in total KOOS scores in both BMAC-PRP and HA groups. However, there were no significant group difference in the study period. In the Sports and Recreational Function Scale, there was statistically significant improvement in the BMAC-PRP group compared to the HA group at three months (p=0.041). There were no side effects or complications in both groups. Conclusion: Intra-articular injection of BMAC-PRP showed better functional recovery in the OA at three months and this can be an alternative treatment in terms of functional recovery in the OA in addition to the decrease of pain.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.3
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• pp.251-262
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• 2022

Purpose: Endoscopic drainage is an established treatment modality for adult patients with pancreatic fluid collections (PFCs). Available data regarding the efficacy and safety of endoscopic drainage in pediatric patients are limited. In this systematic review and meta-analysis, we aimed to analyze the outcomes of endoscopic drainage in children with PFCs. Methods: A literature search was performed in Embase, PubMed, and Google Scholar for studies on the outcomes of endoscopic drainage with or without endoscopic ultrasonography (EUS) guidance in pediatric patients with PFCs from inception to May 2021. The study's primary objective was clinical success, defined as resolution of PFCs. The secondary outcomes included technical success, adverse events, and recurrence rates. Results: Fourteen studies (187 children, 70.3% male) were included in this review. The subtypes of fluid collection included pseudocysts (60.3%) and walled-off necrosis (39.7%). The pooled technical success rates in studies where drainage of PFCs were performed with and without EUS guidance were 95.3% (95% confidence interval [CI], 89.6-98%; I²=0) and 93.9% (95% CI, 82.6-98%; I²=0), respectively. The pooled clinical success after one and two endoscopic interventions were 88.7% (95% CI, 82.7-92.9%; I²=0) and 92.3% (95% CI, 87.4-95.4%; I²=0), respectively. The pooled rate of major adverse events was 6.3% (95% CI, 3.3-11.4%; I²=0). The pooled rate of recurrent PFCs after endoscopic drainage was 10.4% (95% CI, 6.1-17.1%; I²=0). Conclusion: Endoscopic drainage is safe and effective in children with PFCs. However, future studies are required to compare endoscopic and EUS-guided drainage of PFCs in children.

• Clinics in Shoulder and Elbow
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• v.25 no.1
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• pp.73-89
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• 2022

Background: To evaluate the efficacy of autologous platelet-rich plasma (PRP) injections in the treatment of common shoulder diseases. Methods: The PubMed, Medline, and Central databases and trial registries were searched from their inception to October 2020 for randomized controlled trials of autologous PRP injections for shoulder diseases versus placebo or any control intervention. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. The primary outcome was pain intensity (visual analog scale), and secondary outcomes were changes in function and quality of life (QoL). Results: A total of 17 randomized controlled trials of PRP versus control were analyzed. From 8-12 weeks to ≥1 year, PRP injections were associated with better pain relief and functional outcomes than control interventions. PRP injections were also associated with greater QoL, with an effect size of 2.61 (95% confidence interval, 2.01-14.17) at medium-term follow-up. Compared with placebo and corticosteroid injections, PRP injections provided better pain relief and functional improvement. In subgroup analyses, trials in which PRP was prepared by the double centrifugation technique, the platelet concentration in the PRP was enriched ≥5 times, leucocyte-rich PRP was used, or an activating agent was used before application reported the most effective pain relief at 6-7 months. Conclusions: PRP injections could provide better pain relief and functional outcomes than other treatments for persons presenting with common shoulder diseases. PRP injections have a greater capacity to improve shoulder-related QoL than other interventions.