• 대한두경부종양학회지
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• 제38권1호
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• pp.1-9
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• 2022

Thyroid cancer is one of the slow-growing tumors with excellent oncological outcomes. However, a small set of patients with unexpectedly severe outcomes are usually ignored. Anaplastic thyroid cancer (ATC) remains one of the most aggressive and lethal solid tumors. Recently, dabrafenib and trametinib combination therapy or neoadjuvant BRAF induction therapy has shown promising results. In addition, a combination of targeted drugs, immunotherapy, surgery, and radiation therapy can improve overall survival in ATC patients. Another disease for which there is no breakthrough treatment is radioactive iodine-refractory differentiated thyroid cancer (DTC). To date, multikinase inhibitors (sorafenib, lenvatinib) targeting the growth factor signaling pathway have been developed and approved as anticancer agents for patients with advanced DTC. This review includes results from multikinase inhibitors to the emergence of new target molecules, including rearrangements during transformation (RET) and tropomyosin receptor kinase (TRK).

• 생명과학회지
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• 제23권6호
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• pp.812-824
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• 2013

Reserpine은 항고혈압제로서 알츠하이머질병의 증상을 나타내는 Caenorhabditis elegans에서 세포독성을 감소시켜 마비를 억제하고 수명을 연장시키는 것으로 알려져 있다. 본 연구에서는 이러한 reserpine의 효능을 포유동물에서 확인하기 위하여, 알츠하이머질병의 병리적 특성과 연관된 주요인자의 변화를 30일 동안 reserpine을 투여한 Tg2576 마우스에서 관찰하였다. 그 결과, 공격행동(aggressive behavior)은 vehicle 투여 그룹에 비하여 reserpine 투여 그룹에서 유의적으로 감소하였으나 사회적 접촉(social contact)은 유의적인 변화가 없었다. 뇌의 해마부분에서 알츠하이머질병의 원인 중 하나인 $A{\beta}$-42의 축적은 reserpine 투여 그룹에서 유의적으로 감소하였고, $A{\beta}$-42의 농도도 대조군에 비하여 reserpine 투여 그룹에서 감소하였다. 더불어, ${\gamma}$-secretase의 구성단백질 중에서 PS-2, Pen-2, APH-1의 발현은 대조군에 비하여 reserpine 투여군에서 유의적으로 감소하였으나 NCT 발현은 변화가 없었다. 혈청에서 NGF의 농도는 Tg2576 마우스에서 감소하였다가 reserpine 투여한 그룹에서 유의적으로 증가하였으며, high affinity receptor의 신호전달과정에 포함된 단백질 중에서 reserpine 투여 그룹은 TrkA의 인산화가 증가하고 ERK 인산화는 감소되었다. 한편 low affinity receptor의 신호전달과정에서, $p75^{NTR}$과 Bcl-2의 발현은 vehicle 그룹에 비하여 reserpine 투여 그룹에서 유의적으로 발현이 증가하였으나 RhoA의 발현은 reserpine 투여 그룹에서 감소하였다. 따라서 이러한 결과는 reserpine은 포유동물 치매모델인 Tg2576 마우스에서 행동학적 변화, $A{\beta}$-42의 축적, NGF의 농도, NGF신호전달의 변화 등을 유도하며, 향후 치매치료제로서 가능성을 제시하고 있다.

• Archives of Plastic Surgery
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• 제34권1호
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• pp.1-7
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• 2007

Purpose: Human adipose tissue-derived stromal cells(hADSCs) can be expanded in vitro and induced to differentiate into multiple mesenchymal cell types. In this study we have examined various neuronal phenotypes and gene expression profiles of the hADSCs in the neuronal induction. Methods: The hADSCs were isolated from human adipose tissue and they were characterized by the flow cytometry analysis using CD13, CD29, CD34, CD45, CD49d, CD90, CD105 and HLA-DR cell surface markers. We differentiated the hADSCs into the neuronal lineage by using chemical induction medium and observed the cells with contrast microscopy. The immunocytochemistry and western blotting were performed using the NSE, NeuN, Trk-A, Vimentin, N-CAM, S-100 and ${\beta}$-Tubulin III antibodies. Results: The hADSCs were positive for CD13($90.3{\pm}4%$), CD29($98.9{\pm}0.7%$), CD49d($13.6{\pm}6%$), CD90 ($99.4{\pm}0.1%$), CD105($96%{\pm}2.8%$) but negative for CD34, CD45 and HLA-DR. The untreated cultures of hADSCs predominately consisted of spindle shaped cells and a few large, flat cells. Three hours after the addition of induction medium, the hADSCs had changed morphology and adopted neuronal-like phenotypes. The result of immunocytochemistry and western blotting showed that NSE, NeuN, Trk-A, Vimentin, N-CAM, S-100 and ${\beta}$-Tubulin III were expressed. However, NSE, NeuN, Vimentin were weakly expressed in the control. Conclusion: Theses results indicate that hADSCs have the capabillity of differentiating into neuronal lineage in a specialized culture medium. hADSCs may be useful in the treatment of a wide variety of neurological disorders.

• 동의신경정신과학회지
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• 제28권3호
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• pp.231-248
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• 2017

Objectives: This study evaluates anti-stress and sleep-inductive effects of Dongshingihyeolyangsubang (DSGYSB) on rats induced by chronic mild stress (CMS). Methods: Twenty-five healthy rats were randomly divided into five groups: normal, CMS (Control), DSGYSB50, DSGYSB100, and DSGYSBS200. All rats except the normal group were exposed to unpredictable stress conditions such as water deprivation, empty bottles, and forced treadmill. A week after starting the experiment, rats in DSGYSB50, DSGYSB100, and DSGYSB200 groups were fed orally with water once a day for two weeks. Then blood samples were taken from the rats for analysis of complete blood count, AST, ALT, and glucose. Noradrenaline, corticosterone, serotonin, GABA and melatonin were measured by ELISA kit. BDNF, CREB, TrkB and $TNF-{\alpha}$ were measured by RT-PCT. Results: In Noradrenaline contents, the DSGYSB200 group revealed significant decrease compared to the control group. In corticosterone contents, the DSGYSB200 group revealed significant decrease compared to the control group. In serotonin contents, the DSGYSB200 group revealed significant increase compared to the control group. In GABA contents, the DSGYSB50, DSGYSB100, and DSGYSB200 groups revealed significant increase compared to the control group. In the activity of BDNF, the DSGYSB50, DSGYSB100 and DSGYSB200 groups revealed significant increase compared to the control group. In the activity of CREB, the DSGYSB100 and DSGYSB200 groups revealed a significant decrease compared to the control group. In the activity of TrkB, the DSGYSB100 and DSGYSB200 groups revealed significant decrease compared to the control group. In the activity of $TNF-{\alpha}$, DSGYSB100 and DSGYSB200 groups revealed significant decrease compared to the control group. In glucose contents, the DSGYSB100 and DSGYSB200 groups revealed significant decrease compared to the control group. In the leukocyte changes, white blood cells, neutrophil, lymphocytes, and monocyte significantly increased in the DSGYSB100 and DSGYSB200 groups than the control group. In the erythrocyte changes, hemoglobin significantly increased in the DSGYSB200 group than the control group. Conclusions: Results suggest that Dongshingihyeolyangsubang has anti-stress and sleep-inductive effects on rats induced by CMS.

• Biomolecules & Therapeutics
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• 제24권5호
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• pp.469-474
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• 2016

Liriopogons (Liriope and Opiopogon) species are used as a main medicinal ingredient in several Asian countries. The Liriopes Radix (tuber, root of Liriope platyphylla) has to be a promising candidate due to their source of phytochemicals. Steroidal saponins and their glycosides, phenolic compounds, secondary metabolites are considered of active constituents in Liriopes Radix. Spicatoside A, a steroidal saponin, could be more efficacious drug candidate in future. In this review, we summarized the available knowledge on phytochemical and pharmacological activities for spicatoside A. It significantly suppressed the level of NF-${\kappa}B$, NO, iNOS, Cox-2, IL-$1{\beta}$, IL-6 and MAPKs in LPS-stimulated inflammation. The production of MUC5AC mucin was increased. MMP-13 expression was down-regulated in IL-$1{\beta}$-treated cells and reduced glycosaminoglycan release from IL-$1{\alpha}$-treated cells. The neurite outgrowth activity, PI3K, Akt, ERK1/2, TrkA and CREB phosphorylation and neurotropic factors such as NGF and BDNF were upregulated with increased latency time. It also showed cell growth inhibitory activity on various carcinoma cells. From this, spicatoside A exerts anti-inflammation, anti-asthma, anti-osteoclastogenesis, neurite outgrowth, memory consolidation and anticancer activities. Further studies are needed on spicatoside A in order to understand mechanisms of action to treat various human diseases.

• BMB Reports
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• 제28권4호
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• pp.316-322
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• 1995

The GTPase activating protein (GAP) can function both as a negative regulator and an effector of $p21^{ras}$. Overexpression of GAP in NIH-3T3 cells has been shown to inhibit transformation by ms or src. To investigate the function of GAP in a differentiative system, we overexpressed this protein in the nerve growth factor (NGF)-responsive PC12 cell line. Two-fold overexpression of GAP caused a delay of several days in the onset of NGF- but not FGF-induced neuronal differentiation of PC12 cells. However, the NGF-induced activation or tyrosine phosphorylation of upstream (Trk, PLC-${\gamma}1$, SHC) and downstream (B-Raf and $p44^{mapk/erk1}$) components of $p21^{ras}$, signalling cascade was not altered by GAP overexpression. Therefore, the change of phenotype induced by GAP was probably not due to GAP functioning as a negative regulator of $p21^{ras}$. Rather, we found that NGF-induced tyrosine phosphorylation of SNT, a specific target of neurotrophin-induced tyrosine kinase activity, was inhibited by GAP overexpression. SNT is thought to function upstream or independent of $p21^{ras}$. Thus in PC12 cells, overexpressed GAP may control the rate of neuronal differentiation through a pathway involving SNT rather than the $p21^{ras}$ signalling pathway.

• Biomolecules & Therapeutics
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• 제31권2호
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• pp.148-160
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• 2023

Depression is a neuropsychiatric disorder associated with persistent stress and disruption of neuronal function. Persistent stress causes neuronal atrophy, including loss of synapses and reduced size of the hippocampus and prefrontal cortex. These alterations are associated with neural dysfunction, including mood disturbances, cognitive impairment, and behavioral changes. Synaptic plasticity is the fundamental function of neural networks in response to various stimuli and acts by reorganizing neuronal structure, function, and connections from the molecular to the behavioral level. In this review, we describe the alterations in synaptic plasticity as underlying pathological mechanisms for depression in animal models and humans. We further elaborate on the significance of phytochemicals as bioactive agents that can positively modulate stress-induced, aberrant synaptic activity. Bioactive agents, including flavonoids, terpenes, saponins, and lignans, have been reported to upregulate brain-derived neurotrophic factor expression and release, suppress neuronal loss, and activate the relevant signaling pathways, including TrkB, ERK, Akt, and mTOR pathways, resulting in increased spine maturation and synaptic numbers in the neuronal cells and in the brains of stressed animals. In clinical trials, phytochemical usage is regarded as safe and well-tolerated for suppressing stress-related parameters in patients with depression. Thus, intake of phytochemicals with safe and active effects on synaptic plasticity may be a strategy for preventing neuronal damage and alleviating depression in a stressful life.

• Biomolecules & Therapeutics
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• 제31권4호
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• pp.359-369
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• 2023

Dependence receptors are a group of receptor proteins with shared characteristics of transducing two different signals within cells. They can transduce a positive signal of survival and differentiation in the presence of ligands. On the other hand, dependence receptors can transduce an apoptosis signal in the absence of ligands. The function of these receptors depends on the availability of their ligands. Several receptor tyrosine kinases (RTKs) have been reported as dependence receptors. When cells undergo apoptosis by dependence receptors, the intracellular domain of some RTKs is cleaved by the caspases. Among the RTKs that belong to dependence receptors, we focused on eight RTKs (RET, HER2, MET, ALK, TrkC, EphA4, EphB3, and c-KIT) that are cleaved by caspases. In this review, we describe the features of the receptors, their cleavage sites, and the fate of the cleaved products, as well as recent implications on them being used as potential therapeutics for cancer treatment.

• The Plant Pathology Journal
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• 제20권3호
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• pp.172-176
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• 2004

Bacterial isolates TRL2-3 and TRK2-2 showing anti-fungal activity in vitro test against some plant pathogens were identified as Pseudomonas putida and Micrococcus luteus, respectively. Pre-treatment with both bacterial isolates at the concentration 1.0$\times$ $10^7$ and $10^6$cfu/ml in the rhizosphere could trigger induced systemic resistance in the aerial part of cucumber plants against anthracnose caused by Colletotrichum orbiculare. However, the pre-treatment with the higher concentration at 1.0 $\times$ $10^8$ cfu/ml of both isolates could not induce resistance after challenge inoculation with C. orbiculare. As a positive control, the treatment with DL-3 amino butyric acid caused a remarkable reduction of disease severity whereas the lesions on the leaves of untreated plants developed apparently after the fungal inoculation. From these results, it was recomended that disease control using both bacterial isolates inducing systemic resistance in the field where chemical application is forbid.

• Journal of Ginseng Research
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• 제48권5호
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• pp.437-448
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• 2024

Attention deficit hyperactivity disorder (ADHD) is a rapidly increasing neurodevelopmental disorder but currently available treatments are associated with abuse risk, side effects, and incomplete symptom relief. There is growing interest in exploring complementary options, and ginseng has gained attention for its therapeutic potential. This systematic review aimed to assess current evidence on the efficacy of ginseng and its active components, ginsenosides, for ADHD. Eligible studies were identified through searches of PubMed, Embase, Cochrane Library, and Web of Science, up to June 2023. The inclusion criteria included both human and animal studies that investigated the effects of ginseng or ginsenosides on ADHD. The risk of bias was assessed according to study type. Six human studies and three animal studies met the inclusion criteria. The results suggest that ginseng and ginsenosides may have beneficial effects on ADHD symptoms, particularly inattention, through dopaminergic/norepinephrinergicmodulation and BDNF/TrkB signaling. Ginseng and ginsenosides have promising potential for ADHD treatment. Due to limitations in evidence quality, such as the risk of bias and variability in study designs, larger controlled studies are essential. Integrating ginseng into ADHD management may have valuable implications for individuals seeking well-tolerated alternatives or adjunctive therapies.