• Nutrition Research and Practice
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• 제15권1호
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• pp.12-25
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• 2021

BACKGROUND/OBJECTIVES: The study was conducted to investigate the efficacy of the combination treatment of phytochemical resveratrol and the anticancer drug docetaxel (DTX) on prostate carcinoma LNCaP cells, including factors related to detailed cell death mechanisms. MATERIALS/METHODS: Using 2-dimensional monolayer and 3-dimensional spheroid culture systems, we examined the effects of resveratrol and DTX on cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential, apoptosis, and necroptosis by MTT, flow cytometry, and Western blotting. RESULTS: At concentrations not toxic to normal human prostate epithelial cells, resveratrol effectively decreased the viability of LNCaP cells depending on concentration and time. The combination treatment of resveratrol and DTX exhibited synergistic inhibitory effects on cell growth, demonstrated by an increase in the sub-G0/G1 peak, Annexin V-phycoerythrin positive cell fraction, ROS, mitochondrial dysfunction, and DNA damage response as well as concurrent activation of apoptosis and necroptosis. Apoptosis and necroptosis were rescued by pretreatment with ROS scavenger N-acetylcysteine. CONCLUSIONS: We report resveratrol as an adjuvant drug candidate for improving the outcome of treatment in DTX therapy. Although the underlying mechanisms of necroptosis should be investigated comprehensively, targeting apoptosis and necroptosis simultaneously in the treatment of cancer can be a useful strategy for the development of promising drug candidates.

• Asian-Australasian Journal of Animal Sciences
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• 제27권2호
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• pp.187-193
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• 2014

As a result of the cost of grains, the replacement of grains by co-products (i.e. DDGS) in feedlot diets is a common practice. This change produces diets that contain a lower amount of starch and greater amount of fibre. Hypothetically, combining feed grade urea (U) with slow release urea (Optigen) in this type of diet should elicit a better synchrony between starch (high-rate of digestion) and fibre (low-rate of digestion) promoting a better microbial protein synthesis and ruminal digestion with increasing the digestible energy of the diet. Four cannulated Holstein steers ($213{\pm}4$ kg) were used in a $4{\times}4$ Latin square design to examine the combination of Optigen and U in a finishing diet containing different starch:acid detergent fibre ratios (S:F) on the characteristics of digestive function. Three S:F ratios (3.0, 4.5, and 6.0) were tested using a combination of U (0.80%) and Optigen (1.0%). Additionally, a treatment of 4.5 S:F ratio with urea (0.80% in ration) as the sole source of non-protein nitrogen was used to compare the effect of urea combination at same S:F ratio. The S:F ratio of the diet was manipulated by replacing the corn grain by dried distillers grain with solubles and roughage. Urea combination did not affect ruminal pH. The S:F ratio did not affect ruminal pH at 0 and 2 h post-feeding but, at 4 and 6 h, the ruminal pH decreased as the S:F ratio increased (linear, p<0.05). Ruminal digestion of OM, starch and feed N were not affected by urea combination or S:F ratio. The urea combination did not affect ADF ruminal digestion. ADF ruminal digestion decreased linearly (p = 0.02) as the S:F ratio increased. Compared to the urea treatment (p<0.05) and within the urea combination treatment (quadratic, p<0.01), the flow of microbial nitrogen (MN) to the small intestine and ruminal microbial efficiency were greater for the urea combination at a S:F ratio of 4.5. Irrespective of the S:F ratio, the urea combination improved (2.8%, p = 0.02) postruminal N digestion. As S:F ratio increased, OM digestion increased, but ADF total tract digestion decreased. The combination of urea at 4.5 S:F improved (2%, p = 0.04) the digestible energy (DE) more than expected. Combining urea and Optigen resulted in positive effects on the MN flow and DE of the diet, but apparently these advantages are observed only when there is a certain proportion of starch:ADF in the diet.

• Nutrition Research and Practice
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• 제18권5호
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• pp.647-662
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• 2024

BACKGROUND/OBJECTIVES: There is growing interest in herbal medicines for managing age-related diseases, such as Alzheimer's and Parkinson's. Safflower seeds (Carthamus tinctorius L. seeds, CTS) and dandelions (Taraxacum coreanum, TC) are widely used to treat bone- or inflammation-related diseases in Oriental countries. This study investigated the protective effect of the CTS-TC combination on scopolamine (Sco)-induced memory deficits through inflammatory response and cholinergic function. Moreover, marker components such as serotonin, N-(p-coumaroyl) serotonin, N-feruloylserotonin, chlorogenic acid, and chicoric acid in the CTS-TC combination were analyzed for their potential benefits on memory function. MATERIALS/METHODS: Water extracts of CTS, TC, and the CTS-TC combination at various ratios (4:1, 1:1, and 1:4) (100 mg/kg) were orally administered to mice for 14 days. Sco (1 mg/kg) was intraperitoneally injected into the mice before each behavioral test. T-maze and novel object recognition tests were conducted to monitor behavioral changes after the treatment. Western blotting was performed to detect protein expression. In addition, the presence of 5 biomarkers, serotonin, N-(p-coumaroyl) serotonin, N-feruloylserotonin, chlorogenic acid, and chicoric acid, was analyzed using high-performance liquid chromatography (HPLC). RESULTS: Behavioral tests showed that the CTS-TC combination enhanced memory function in Sco-injected mice. Inflammation-related proteins (inducible nitric oxide synthase, cyclooxygenase-2, and glial fibrillary acidic protein) were downregulated after treatment with the CTS-TC combination. The acetylcholinesterase protein expression was also downregulated. HPLC analysis revealed that N-feruloylserotonin and chicoric acid were the predominant components, followed by N-(p-coumaroyl) serotonin, chlorogenic acid, and serotonin. CONCLUSION: These findings suggest that the CTS-TC combination protects against Sco-induced memory deficits by inhibiting inflammatory responses and cholinergic dysfunction. N-feruloylserotonin and chicoric acid, along with N-(p-coumaroyl) serotonin, chlorogenic acid, and serotonin, might be biomarkers for the CTS-TC combination, and their effects on memory protection warrant further study.

• Journal of Acupuncture Research
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• 제39권2호
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• pp.122-133
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• 2022

Background: This study was designed to statistically analyze the data of patients who had Bell's palsy (BP) who visited a Korean Medicine hospital in the last 3 years to determine the tendency or characteristics of their visit. Methods: This study retrospectively analyzed the medical records of 816 patients. Based on the data collected through medical records demographics, condition/disease, and therapeutic characteristics of the patients were analyzed using IBM SPSS Version 23.0. Results: Patients in their teens or younger, and 50s or older had a higher frequency of inpatient treatment, and 20s to 40s had a higher rate of outpatient treatment. The proportion of men who received steroid combination treatment was higher than women. The number of patients with BP, and the total treatment period of the patients has decreased every year. The total treatment period was shorter in the steroid group than the Korean medicine alone group. Inpatients were more likely to receive steroid combination therapy than outpatients. The proportion of patients who received steroid combination therapy was higher than patients with recurrence of BP. Patients with hypertension or diabetes had a higher rate of hospitalization and received more treatments than patients without the condition/disease. Conclusion: Visit characteristics and treatment methods preferred by patients with BP were identified. This research may help to establish a treatment model for BP in Korean Medicine institutions in the future.

• Journal of Gastric Cancer
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• 제23권1호
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• pp.224-249
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• 2023

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

• 척추신경추나의학회지
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• 제17권2호
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• pp.91-100
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• 2022

Objectives The purpose of this study was to report a case of a woman diagnosed with post hysterectomy syndrome treated with combined Korean medical treatment. Methods A combination of treatment including chuna manual therapy, pharmacopuncture at the lumbar facet joints, acupuncture, cupping, and herbal medicine was provided for 1 month. Progress was assessed using the Numeric Rating Scale, Oswestry Disability Index, EuroQol-5Dimension, and Hot Flush Score before and after treatment. Results After treatment, the symptoms were reduced and the quality of life was enhanced, although there was no improvement in the abnormal sensation in the anterior part of the thigh. No adverse events were observed. Conclusions The findings indicate that a combination of Korean medical treatment can be a safe and effective alternative treatment in reducing LBP and hot flushes after hysterectomy.

• 대한두경부종양학회지
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• 제16권2호
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• pp.228-234
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• 2000

Objectives: Esthesioneuroblastoma is a rare malignant neoplasm that originates from the olfactory sensory cells. This tumor grows from the upper nasal cavity and ethmoid sinus and invades surrounding structures through the cribriform plate into intracranium or orbit in advanced stage. Even though there has been some controversies in determining standard treatment due to rarity of this tumor, the combination treatment of surgery and adjuvant radiation has been recommended for the locally advanced esthesioneuroblastomas. However, the recent clinical experiences of advanced cases showed that combination chemotherapy is highly effective to reduce tumor mass and improve clinical outcomes. Materials and Methods: The authors conducted a retrospective analysis of 6 esthesioneuroblastoma patients who were treated in our hospital from 1986. Results: The age of these patients was between 19 and 86 year-old. Among the 6 cases, 2 were diagnosed at stage B and 4 at stage C, according to Kadish classification. Anti-tumor treatments were performed in 5 patients. One patient refused active treatment and was lost to follow-up. Better survival outcome were observed in 3 patients who were treated with combination chemotherapy alone or combined modality treatment including chemotherapy. Conclusion: Based on our retrospective study, the combined treatment consisting of surgery, radiotherapy, and combination chemotherapy should be used to improve treatment results. And furthermore, innovative clinical approaches such as neoadjuvant chemotherapy, high-dose chemotherapy and autologous peripheral stem cell transplantation, which have been reported to have good therapeutic results, should be considered and applied actively.

• Tuberculosis and Respiratory Diseases
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• 제56권4호
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• pp.381-392
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• 2004

연구배경 : Arsenic trioxide($As_2O_3$)은 재발성 또는 불응성 급성전골수성백혈병의 치료제로 쓰이는 항암제로서 비소세포폐암을 포함한 다른 암세포주에도 효과가 있는 것으로 되어있다. NSAIDs는 항암 예방약제로 사용되고 있고, 세포고사를 통해 다른 항암제나 방사선치료의 반응성을 강화시키는 것으로 알려져 있다. 저자들은 NCI-H157 세포주에서 $As_2O_3$와 sulindac의 병합치료가 그것들의 세포고사를 배가시키는지 여부를 알아보고자 하였다. 방 법 : 세포 독성은 MTT 방법으로 측정하였고, 세포고사를 알아보기 위해 핵산 염색과 유식세포 분석을 시행하였다. 세포고사의 기전을 보기 위해 caspasefamily의 활성을 보았고, PARP와 ICAD의 분절을 western blotting으로 확인하였다. 또한 Fas와 Fas-L의 발현유무를 western blotting을 통해 관찰하였다. 결 과 : NCI-H157 폐암세포에 $As_2O_3$와 sulindac을 병합치료시 단독치료군에 비해 생존율이 의미 있게 감소하였고, 이러한 세포사는 핵산염색을 통한 염색사의 응축과 핵 분절 유도와 유식세포 분석에 의한 $sub-G_0/G_1$ DNA분획의 증가현상을 통해 세포고사에 의해 매개됨을 알 수 있었다. 세포고사의 유도에는 caspase 3, 8, 9를 통한 활성화와 이에 의한 PARP와 ICAD의 절단을 확인하였다. 또한 caspase-8 protease의 활성화에는 Fas와 Fas/L 단백질의 발현증가가 유도되었음을 알 수 있었다. 결 론 :NCI-H157 폐암세포주에 $As_2O_3$와 sulindac의 병합요법은 Fas/FasL 신호전달계의 활성화와 caspase 단백질 활성화 의해 세포고사가 유도되었다.

• 대한한방부인과학회지
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• 제24권2호
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• pp.1-12
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• 2011

Objectives: The object of this study was to observe the in vitro antibacterial effects of Chungdae-tang aqueous extracts, traditionally used for treating various gynecological diseases including vaginitis in Korea against Gardnerella vaginalis, and combination effects of Chungdae-tang extracts with Clindamycin were also monitored in this study. Methods: Antibacterial activities against Gardnerella vaginalis of Chungdae-tang aqueous extracts were detected using standard agar microdilution methods. In addition, the effects on the bacterial growth curve were also monitored at MIC and MIC${\times}$2 levels. The combination effects of Chungdae-tang aqueous extracts with Clindamycin were observed by Checkerboard microtiter assay, and the effects of bacterial growth curve treated with or Chungdae-tang aqueous extracts MIC+Clindamycin MIC, 1/2MIC and 1/4MIC, respectively. In the present study, Gardnerella vaginalis were incubated under $37^{\circ}C$, 10% $CO_2$; and bacterial growth curves were calculated at 24, 48, 72, 96 and 120hrs after incubations. Results: MIC of Chungdae-tang aqueous extracts against Gardnerella vaginalis were detected as $3.906{\pm}2.344$(0.782~6.250) mg/$m\ell$, respectively. MIC of Clindamycin was detected as $0.010{\pm}0.006$(0.004~0.016) ${\mu}g/m\ell$ at same conditions. In addition, Clindamycin and Chungdae-tang aqueous extracts also showed marked dosage-dependent inhibition of bacterial growth, and more dramatical inhibitions were detected in Clindamycin+Chungdae-tang aqueous extracts MIC treatment as compared with each of single Clindamycin MIC and Chungdae-tang aqueous extracts MIC treatments, respectively. In addition, quite similar inhibitory effects on bacterial growth were detected in Clindamycin 1/4 MIC+Chungdae-tang aqueous extracts MIC treatment as compared with single Clindamycin MIC treatment in the present study. FIC index in combination of Chungdae-tang and Clindamycin were detected as $0.775{\pm}0.285$ (0.500~1.250) at Checkerboard microtiter assay. Conclusions: The results obtained in this study suggest that Chungdae-tang aqueous extracts showed antibacterial effects against Gardnerella vaginalis, and it also showed dosage-dependent inhibitory effects on the bacterial growth. In addition, combination treatment of Chungdae-tang aqueous extract with Clindamycin showed more potent inhibitory effects on the growth of Gardnerella vaginalis with FIC index $0.775{\pm}0.285$(0.500~1.250), respectively. It means, the combination of Chungdae-tang aqueous extract with Clindamycin is partially synergistic effects. It, therefore, is expected that effective dosages of Clindamycin will be reduced to 1/4 or over 1/4 levels as combination with Chungdae-tang extracts, respectively.

• Journal of Acupuncture Research
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• 제33권2호
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• pp.135-150
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• 2016

Objectives : The aim of this study is to review the combination effects and adverse effects of Yerba Mate (Ilex paraguariensis) on the treatment of obesity. Methods : Four databases were searched, including Pubmed, National assembly library, RISS4u, and NDSL, for studies published before March 31, 2016 using the keywords 'yerba mate', 'Ilex paraguariensis', and those related to 'obesity'. Clinical trials, and both in vivo and in vitro studies were classified according to the following categories: publication year, nationality, types and composition of test compounds, combination effects, adverse effects, and safety. Results : A total of 16 articles (14 clinical trials, one in vivo, one in vitro) were included in the analysis. Combination effects were reported from six YGD (Yerba Mate, Guarana, Damiana, Zotrim), five Meltdown, one Shred-matrix, one DBX (DymaBurn Xtreme), one XSIII research study, and adverse effects were reported from two YGD (Zotrim), four Meltdown, one Shred-matrix and one MetEF research study. YGD and Shred-matrix increased satiety while YGD and MetEF had adverse gastrointestinal effects potentially due to guarana. Meltdown and Shred-matrix increased energy expenditure and fat oxidation and had the adverse effects of increased heart rate and blood pressure due to the thermogenic effect of caffeine and yohimbine. DBX increased resting energy expenditure but no difference was observed in respiratory exchange ratio. XSIII reduced body weight gain and food intake more than each of the extracts did on their own. Conclusion : Taken together, the combination effects and adverse effects differed according to the composition of test compounds and the ratio of ingredients. Multicomponent approaches should be used for treating multifactorial diseases such as obesity. As a general conclusion, there is a place for a combination of herbal components including yerba mate, based on the principle of Kun-Shin-Choa-Sa for the treatment of obesity.