• The Korean Journal of Pain
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• v.32 no.4
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• pp.245-255
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• 2019

Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells, commonly encountered in clinical or preclinical stages, are largely classified into embryonic, adult, and induced pluripotent stem cells. Recently, stem cell transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain which do not respond to conventional medicine. The main idea of applying stem cells to neuropathic pain is based on the ability of stem cells to release neurotrophic factors, along with providing a cellular source for replacing the injured neural cells, making them ideal candidates for modulating and possibly reversing intractable neuropathic pain. Even though various differentiation capacities of stem cells are reported, there is not enough knowledge and technique to control the differentiation into desired tissues in vivo. Even though the use of stem cells is still in the very early stages of clinical use and raises complicated ethical problems, the future of stem cells therapies is very bright with the help of accumulating evidence and technology.

• Biomedical Science Letters
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• v.25 no.3
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• pp.247-255
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• 2019

Curcuma longa L. (C.L), Curcuma aromatica Salisb. (C.A) and Zingiber officinale Rosc. (Z.O) of Zingiberaceae plants which are well known as effects of natural anti-oxidant, anti-cancer and anti-inflammatory. We examined that the Zingiberaceae plants are involved in development and modulation of orofacial pain in rats. Male, 7- to 8-week-old, Sprague-Dawley rats weighing 240~280 g were used in this study. Experiments were performed using acute pain model that was caused by the injection of 5% formalin into the right vibrissa pad. The number of scratching or rubbing to the injection site was recorded for 9 consecutive 5-minute intervals following injection of formalin. The experimental groups were acute orofacial inflammatory pain; control group (formalin, 5%), vehicle group (5% formalin after sodium carboxymethyl cellulose), single administration group, single mixed administration group, repeated administration group. The experiments were performed various concentrations of Zingiberaceae plants extract. Therefore, oral administration of C.L, C.A, and Z.O (p.o., concentrations of 12.5, 25 mg/mL) in orofacial inflammatory pain model substantially decrease the nociceptive behavior in a concentration dependent manner. And it tended to decrease at low concentration (12.5 mg/mL) of single mixed and repeated administration more than single administration. This result means that Zingiberaceae plants extract affects the modulation of acute orofacial inflammatory pain. Thus, Zingiberaceae plants extract may be a potential therapeutic treatment for orofacial inflammatory pain.

• International Journal of Oral Biology
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• v.46 no.1
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• pp.23-29
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• 2021

Demethoxycurcumin (DMC), which is a curcuminoid found in turmeric, has anti-proliferative effects on cancer cells. However, the effect of DMC on osteosarcoma has not been established. The aim of this study was to examine the effects of DMC on cell growth and apoptosis induction in MG-63 human osteosarcoma cells. This study was investigated using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromid assay, Live/Dead cell assay, 4', 6-diamidino-2-phenylindole staining, and immunoblotting in MG-63 cells. DMC induced MG-63 cell death in a dose-dependent manner, with an estimated IC50 value of 54.4 µM. DMC treatment resulted in nuclear condensation in MG-63 cells. DMC-induced apoptosis in MG-63 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting results showed that Bcl-2 and Bcl-xL were downregulated, while Bax and Bad were upregulated by DMC in MG-63 cells. These results indicated that DMC inhibits cell proliferation and induces apoptotic cell death in MG-63 human osteosarcoma cells via the death receptor-mediated extrinsic apoptotic pathway and mitochondria-mediated intrinsic apoptotic pathway.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.545-550
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• 2021

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.

• Journal of Yeungnam Medical Science
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• v.39 no.3
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• pp.235-243
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• 2022

Background: Intrahepatic cholangiocarcinoma (ICC) of the left liver often shows left-sided lymph node (LN) metastasis. If gastric lesser curvature is extensively dissected, it can induce an iatrogenic injury to the extragastric vagus nerve branches that control motility of the pyloric sphincter and lead to gastric stasis. To cope with such LN dissection-associated gastric stasis, we performed pyloroplasty preemptively. The objective of this study was to analyze our 20-year experience of preemptive pyloroplasty performed in 10 patients. Methods: We investigated clinical sequences of 10 patients with ICC who underwent preemptive pyloroplasty following left hepatectomy and extended left-sided LN dissection. Incidence of gastric stasis and oncological survival outcomes were analyzed. Results: All 10 patients were classified as stage IIIB due to T1-3N1M0 stage according to the 8th edition of American Joint Committee on Cancer staging system. The overall patient survival rate was 51.9% at 1 year, 25.9% at 2 years, and 0% at 3 years. Seven patients showed uneventful postoperative recovery after surgery. Two patients suffered from gastric stasis, which was successfully managed with supportive care. One patient suffered from overt gastric paresis, which was successfully managed with azithromycin administration for 1 month. Conclusion: We believe that preemptive pyloroplasty is an effective surgical option to prevent gastric stasis in patients undergoing extensive left-sided LN dissection. Azithromycin appears to be a potent prokinetic agent in gastroparesis.

• BMB Reports
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• v.54 no.12
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• pp.608-613
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• 2021

Melanoma, the most serious type of skin cancer, exhibits a high risk of metastasis. Although chemotherapeutic treatment for metastatic melanoma improves disease outcome and patient survival, some patients exhibit resistance or toxicity to the drug treatment regime. OTUB1 is a deubiquitinating enzyme overexpressed in several cancers. In this study, we investigated the effects of inhibiting OTUB1 expression on melanoma-cell proliferation and viability and identified the underlying molecular mechanism of action of OTUB1. We did endogenous OTUB1 knockdown in melanoma cells using short interfering RNA, and assessed the resulting phenotypes via MTT assays, Western blotting, and cell-cycle analysis. We identified differentially expressed genes between OTUB1-knockdown cells and control cells using RNA sequencing and confirmed them via Western blotting and reverse transcription polymerase chain reaction. Furthermore, we investigated the involvement of apoptotic and cell survival signaling pathways upon OTUB1 depletion. OTUB1 depletion in melanoma cells decreased cell viability and caused simultaneous accumulation of cells in the sub-G1 phase, indicating an increase in the apoptotic-cell population. RNA sequencing of OTUB1-knockdown cells revealed an increase in the levels of the apoptosis-inducing protein TRAIL. Additionally, OTUB1-knockdown cells exhibited increased sensitivity to PLX4032, a BRAF inhibitor, implying that OTUB1 and BRAF act collectively in regulating apoptosis. Taken together, our findings show that OTUB1 induces apoptosis of melanoma cells in vitro, likely by upregulating TRAIL, and suggest that approaches targeting OTUB1 can be developed to provide novel therapeutic strategies for treating melanoma.

• Journal of the Korean Society of Food Culture
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• v.37 no.6
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• pp.503-509
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• 2022

Methylglyoxal is a highly reactive precursor which forms advanced glycation end products (AGEs). AGEs and methylglyoxal are known to induce various diseases such as diabetes, vascular disorders, Diabetes Mellitus (DM), and neuronal disorders. Juglans regia L is an important food commonly used worldwide, having nutritious components, including phenolic compounds. Since ancient times, Juglans regia L have been differently applied by various countries for health and in diverse diseases, including arthritis, asthma, skin disorders, cancer, and diabetes mellitus. However, the effect of diabetes-induced renal damage against AGEs remains unclear. This study evaluates the anti-glycation and renal protective effects of ethanol extract of Juglans regia L against methylglyoxal-induced renal tubular epithelial cell death. Exposure to methylglyoxal resulted in reduced cell viability in NRK-52E cells, but co-treatment with Juglans regia L extracts significantly increased the cell viability. In addition, we examined the anti-glycation effect of Juglans regia L extracts. Compared to the positive control aminoguanidine and Alagebrium, treatment with Juglans regia L extracts significantly inhibited the formation of AGEs, collagen cross-linking, and breaking collagen cross-linking. Taken together, our results indicate that Juglans regia L is a potential therapeutic agent for regulating diabetic complications by exerting anti-glycation and renal protective activities.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.69-74
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• 2013

Objectives : Since hypopigmentation is known to increase the risk of skin cancer, melanogenesis in the skin needs to be regulated. Here, we evaluated the melanogenesis stimulatory effects of a modified Goagium herbal remedy (HR) and HR+ox bile (Bos taurus domesticus) extract (OBE) to address hypopigmentation disorders. Methods : B16F10 melanoma cells were treated with different dosages of HR and HR+OBE for 24 to 48 h after 1 h of 10 nM ${\alpha}$-melanocyte stimulating hormone (${\alpha}$-MSH). After the treatment, cell viability, tyrosinase activity, melanin synthesis and the expression of genes related to melanin synthesis were measured and the regulation of the ${\alpha}$-MSH signalling through cAMP responding element binding protein (CREB) was determined. Results : HR and HR+OBE with the ranges of $15{\sim}100{\mu}g/mL$ did not affect cell viability in melanoma cells. The 1 h treatment of HR+OBE (50 and $100{\mu}g/mL$) potentiated the phosphorylation of CREB by enhancing ${\alpha}$-MSH signaling and its 24 h treatment increased CREB expression. Consistent with CREB potentiation, their treatment for 24 h, the expression of microphthalmia-associated transcription factor (MIFT), tyrosinase, tyrosinase related protein (TRP)-1 and TRP-2 were increased in realtime PCR. Ultimately, the 48 h treatment of HR+OBE (50 and $100{\mu}g/mL$) increased tyrosniase activity and melanin contents in the melanoma cells in comparison to the control. Conclusions : HR+OBE (50 and $100{\mu}g/mL$) increases melanin synthesis in B16F10 melanoma cells via the stimulation of tyrosinase activity and expression of MIFT, tyrosinase, TRP-1 and TRP-2. HR+OBE can be used as the a possible treatment for hypopigmentation of the skin.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.1-7
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• 2013

Objectives : The root of Peucedanum japonicum Thunberg (Peucedani Japonici Radix; PJR) has been traditionally used as an herbal medicine for the treatment of anti-headache, anti-paralysis, anti-cancer, vascular protection, and blood pressure regulation. In this study, we investigated the anti-allergic effect of PJR water extract on ovalbumin (OVA)-induced allergic asthma in mice. Methods : Mice were sensitized at days 1, 8 and 15 with OVA and airway challenged at days 22, 24, 26, 28, and 30 to induced allergic asthma. PJR-W extract at doses of 100 and 300 mg/kg/body weight (bw) was orally administered during OVA challenge once per a day. The levels of allergic mediators such as immunoglobulin (Ig) E, and Th1/Th2 cytokines (IFN-${\gamma}$ and IL-4) were measured in the sera of mice by ELISA. The histological change of lung tissue was observed with hematoxylin and eosin (H&E) staining. Results : The administration of PJR-W extract significantly decreased the serum levels of IgE, IL-4, and IFN-${\gamma}$ compared with those of OVA control group. In H&E staining, PJR-E extract inhibited OVA-induced airway inflammation and the inflammatory cells infiltration in the peribronchial regions of the lung. Conclusions : These results indicate that PJR-W extract has an anti-inflammatory and anti-allergic effect on allergic response through the down-regulation of allergic mediators, suggesting that this herb may be used as a useful source for the treatment of allergic inflammatory diseases such as asthma.

• The Korea Journal of Herbology
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• v.33 no.2
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• pp.79-84
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• 2018

Objective : The immune enhance is the main focus of current society that to increase resistance to invasion by pathogenic species of bacteria in body, stimulate the immune system and possibly protect against cancer or inflammatory disease. The present study aimed to evaluate the effect of Gentianae Radix extract on immune regulation in a LPS-induced mice model of acute inflammation. Methods : Gentianae Radix extract was administered orally at doses of 200 mg/kg/day or 400 mg/kg/day for 2 weeks before a intraperitoneally injection of LPS (1 mg/kg of 0.9% saline). After LPS-intraperitoneal injection 3 hours, blood was collected by cardiac puncture under ether anaesthesia from all animals, for the immune regulate efficacy verification based on blood or serum biomarkers (i.e., immune cells, cytokine, $PGE_2$, ROS, and $LTB_4$) analysis. Results : Compared to the control mice, the Gentianae Radix extract treatments significantly increased the count of immune cells (i.e., wite blood cell, neutrophils, and monocyte), and significantly reduced the lymphocyte. In addition, the Gentianae Radix extract treatments significantly decreased the pro-inflammatory cytokine (i.e., $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$), and significantly increased IL-10 of anti-inflammatory cytokine. Furthermore, the Gentianae Radix extracts treatments significantly increased the levels of $PGE_2$ and significantly decreased the levels of ROS, and $LTB_4$. Conclusions : The results indicate that Gentianae Radix extract alleviated acute inflammatory reaction though regulation of immune meditor. Thus, Gentianae Radix extract may raw material of development a health food and medicine option for the immune enhance.