• Title/Summary/Keyword: Parkinson/s

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CD206+ dendritic cells might be associated with Heat-pattern and induced regulatory T cells after treatment with bee venom

  • Jung, Woo-Sang;Kwon, Seungwon;Yang, Jung Yun;Jin, Chul;Cho, Seung-Yeon;Park, Seong-Uk;Moon, Sang-Kwan;Park, Jung-Mi;Ko, Chang-Nam;Bae, Hyunsu;Cho, Ki-Ho
    • The Journal of Korean Medicine
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    • v.43 no.2
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    • pp.1-7
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    • 2022
  • Objectives: Bee venom (BV) is a widely used therapy in Traditional East Asian Medicine (TEAM). We previously reported that BV was clinically effective for treating Parkinson's disease, that phospholipase A2 (PLA2) was the main component of BV, and that it induced regulatory T cells (Tregs) by binding CD206 on dendritic cells (DCs). Therefore, we aimed to reconfirm our findings in human blood samples and investigate the relationship between CD206+ DCs and clinical syndrome differentiation in TEAM. Methods: We surveyed 100 subjects with questionnaires on cold-heat patternization and obtained their blood samples. The obtained human peripheral blood monocytes (hPBMCs) were washed with phosphate-buffered saline (PBS). After resuspension with ex vivo media, numbers of cells were counted. Tregs were counted after culturing the samples in a 37℃ CO2 incubator for 72 h. Results: We divided the subjects into a relatively high CD206+ group or a relatively low CD206+ group. The heat factor scores of high CD206+ group were significantly higher than that of low CD206+ group (high vs low: 239.2 ± 54.1 vs 208.4 ± 55.1, p=0.023). After culturing with PLA2, Tregs increased in the high CD206+ group but decreased in the low CD206+ group. Conclusion: In this study, we reconfirm that CD206+ DCs induced Treg differentiation by incubating human blood samples with PLA2 and that they showed an association with syndrome differentiation, especially with heat patterns, in TEAM. A heat pattern in TEAM might be one indication for PLA2 therapy because its score was elevated in the high CD206+ group.

Neuroprotective Effects of Parkin and Bcl-2 against Dieldrin-induced Endoplasmic Reticulum Stress (디엘드린 유도성 소포체 스트레스에서의 parkin과 Bcl-2의 신경보호 효과)

  • Seo, Jeong-Yeon;Kim, Jae-Sung;Kim, Do Kyung;Chun, Hong Sung
    • Journal of Life Science
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    • v.32 no.10
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    • pp.771-777
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    • 2022
  • Dopaminergic (DA) cell death in Parkinson's disease (PD) has been attributed to multiple, distinct genetic and environmental factors. In rare familial PD loss of parkin function mutations play a key role in nigral DA neuron-specific pathogenesis primarily via endoplasmic reticulum (ER) stress. In more prevalent sporadic PD, environmental exposure to pesticides has a significant epidemiological role. However, it is largely unknown how environmental exposure to xenobiotics is etiologically linked with the known etiology in familial PD. In the present study biochemical evidence for a common pathogenic mechanism between sporadic and familial PD has been identified employing the recently characterized mesencephalic DA cell line, N27-A. Dieldrin, an organochlorine pesticide epidemiologically implicated in sporadic PD, induced the markers of ER stress response such as a chaperone BiP/Grp78, heme oxygenase-1 and especially, parkin. Accordingly, dieldrin activated the ER resident Caspase-12, a mediator of ER stress-specific apoptosis, during cell death of N27-A cells. Of great interest the dieldrin-induced DA neuronal cell death was synergistically rescued by the overexpression of ER resident neuroprotective proteins, parkin and Bcl-2. The present findings implicate that accumulation of ER stress could be one of common pathogenic mechanisms in idiopathic and familial PD, and some ER proteins, such as parkin and Bcl-2 may effectively attenuate ER stress-mediated N27-A DA cell death.

Antioxidative Effects of Parnassia palustris L. Extract on Ferrous Sulfate-Induced Cellular Injury of Cultured C6 Glioma Cells (파킨슨씨병 유발물질인 황산철로 손상된 배양 신경아교세포에 대한 물매화 추출물의 항산화 효과)

  • Young-Mi, Seo;Seung-Bum, Yang
    • Korean Journal of Clinical Laboratory Science
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    • v.54 no.4
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    • pp.298-306
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    • 2022
  • This study sought to evaluate the mechanism of cellular injury caused by ferrous sulfate (FeSO4) and the protective effects of Parnassia palustris L. (PP) extract against FeSO4-induced cytotoxicity of cultured C6 glioma cells. FeSO4 is known to cause neurotoxicity and induce Parkinson's disease. The antioxidative effects of PP, such as superoxide dismutase (SOD)-like and superoxide anion-radical (SAR)-scavenging activities, as well as effects on cell viability, were studied. FeSO4 significantly decreased cell viability in a dose-dependent manner and the XTT50 value, the concentration of FeSO4 which reduced the cell viability by half, was measured at 63.3 μM in these cultures. FeSO4 was estimated to be highly cytotoxic by the Borenfreund and Puerner toxicity criteria. Quercetin, an antioxidant, significantly improved cell viability, damaged by FeSO4-induced cytotoxicity. While evaluating the protective effects of the PP extract on FeSO4-induced cytotoxicity, it was observed that the extract significantly increased cell viability compared to the FeSO4-treated group. Also, the PP extract showed superoxide dismutase (SOD)-like and superoxide anion radical (SAR)-scavenging activities. Based on these findings, it can be concluded that FeSO4 induced oxidative stress-related cytotoxicity, and the PP extract effectively protected against this cytotoxicity via its antioxidative effects. In conclusion, natural antioxidant sources such as PP may be agents useful for preventing oxidative stress-related cytotoxicity induced by heavy metal compounds such as the FeSO4, a known Parkinsonism inducer.

A Case Report of a Progressive Supranuclear Palsy Patient with Gait Disturbance and Dizziness (보행장애 및 현훈을 호소하는 진행성 핵상마비 환자 치험 1례)

  • Cho, Jae Hyun;Park, Hye Lim;Hong, Minna;Lee, Hye Yoon;Lee, Ji Hye;Kim, So Yeon;Choi, Jun Yong;Han, Chang Woo;Yun, Young Ju;Park, Seong Ha;Hong, Jin Woo;Lee, In;Kwon, Jung Nam
    • The Journal of the Society of Stroke on Korean Medicine
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    • v.16 no.1
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    • pp.25-34
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    • 2015
  • ■ Objectives The purpose of this case report is to show the effect of korean medicine on a progressive supranuclear palsy patient with gait disturbance and dizziness. ■ Methods A patient with gait disturbance and dizziness diagnosed as progressive supranuclear palsy was treated with herbal medicine, acupuncture, electro-acupuncture, moxibustion. The period of admission is 16 days and we evauated the improvements of symptoms by the Unified Parkinson's Disease Rating Scale(UPDRS), Numeric Rating Scale(NRS) and Global Assessment(G/A). ■ Results After taking Modified Bosimhwan andbeing treated by acupuncture therapy, improvements of gait disturbance and dizziness are observed. ■ Conclusion This case report proved the effect of Korean medicine on progressive supranuclear palsy.

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Correlation of Protumor Effects of Leucine-Rich Repeat Kinase 2 with Interleukin-10 Expression in Lung Squamous Cell Carcinoma (폐 편평세포암종 내 Leucine-Rich Repeat Kinase 2 암촉진 효과와 Interleukin-10 발현과의 연관성)

  • Sung Won LEE;Sangwook PARK
    • Korean Journal of Clinical Laboratory Science
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    • v.55 no.2
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    • pp.105-112
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    • 2023
  • Leucine-rich repeat kinase 2 (LRRK2) is known to play a crucial role in the pathophysiology of neurodegenerative disorders such as Parkinson's disease. LRRK2 is predominantly expressed in the lung as well as the brain. However, it is unclear whether LRRK2 expression correlates with the pathogenesis of lung squamous cell carcinoma (LUSC). This study analyzes the prognostic significance of LRRK2 in LUSC using the Kaplan-Meier plotter tool. High expression of LRRK2 is known to be associated with a bad prognosis in patients with LUSC. Patients with high LRRK2 expression, tumor mutational burden, high neoantigen load, and even gender correlation reportedly have the worse survival rates. In the gene expression profiling interactive analysis (GEPIA) database, the severity of pathogenesis in LUSC with high LRRK2 expression positively corresponds to a high expression of anti-inflammatory cytokines but not inflammatory cytokines. Similarly, the increased expression of interleukin (IL)10-related genes was shown to be significantly linked in LRRK2-high LUSC patients having a poor prognosis. Moreover, the tumor immune estimation resource (TIMER) database suggests that macrophages are one of the cellular sources of IL10 in LRRK2-high LUSC patients. Collectively, our results demonstrate that the postulated LRRK2-IL10 axis is a potential therapeutic target and prognostic biomarker for LUSC.

Neurotechnologies and civil law issues (뇌신경과학 연구 및 기술에 대한 민사법적 대응)

  • SooJeong Kim
    • The Korean Society of Law and Medicine
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    • v.24 no.2
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    • pp.147-196
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    • 2023
  • Advances in brain science have made it possible to stimulate the brain to treat brain disorder or to connect directly between the neuron activity and an external devices. Non-invasive neurotechnologies already exist, but invasive neurotechnologies can provide more precise stimulation or measure brainwaves more precisely. Nowadays deep brain stimulation (DBS) is recognized as an accepted treatment for Parkinson's disease and essential tremor. In addition DBS has shown a certain positive effect in patients with Alzheimer's disease and depression. Brain-computer interfaces (BCI) are in the clinical stage but help patients in vegetative state can communicate or support rehabilitation for nerve-damaged people. The issue is that the people who need these invasive neurotechnologies are those whose capacity to consent is impaired or who are unable to communicate due to disease or nerve damage, while DBS and BCI operations are highly invasive and require informed consent of patients. Especially in areas where neurotechnology is still in clinical trials, the risks are greater and the benefits are uncertain, so more explanation should be provided to let patients make an informed decision. If the patient is under guardianship, the guardian is able to substitute for the patient's consent, if necessary with the authorization of court. If the patient is not under guardianship and the patient's capacity to consent is impaired or he is unable to express the consent, korean healthcare institution tend to rely on the patient's near relative guardian(de facto guardian) to give consent. But the concept of a de facto guardian is not provided by our civil law system. In the long run, it would be more appropriate to provide that a patient's spouse or next of kin may be authorized to give consent for the patient, if he or she is neither under guardianship nor appointed enduring power of attorney. If the patient was not properly informed of the risks involved in the neurosurgery, he or she may be entitled to compensation of intangible damages. If there is a causal relation between the malpractice and the side effects, the patient may also be able to recover damages for those side effects. In addition, both BCI and DBS involve the implantation of electrodes or microchips in the brain, which are controlled by an external devices. Since implantable medical devices are subject to product liability laws, the patient may be able to sue the manufacturer for damages if the defect caused the adverse effects. Recently, Korea's medical device regulation mandated liability insurance system for implantable medical devices to strengthen consumer protection.

Anti-neuroinflammatory Effect of Teleogryllus emma Derived Teleogryllusine in LPS-stimulated BV-2 Microglia (BV-2 미세아교세포에서 왕귀뚜라미 유래 Teleogryllusine의 신경염증 억제 효과)

  • Seo, Minchul;Shin, Yong Pyo;Lee, Hwa Jeong;Baek, Minhee;Lee, Joon Ha;Kim, In-Woo;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.30 no.11
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    • pp.999-1006
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    • 2020
  • The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH2) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.

Inhibitory Effect of Protaetia brevitarsis seulensis Ethanol Extract on Neuroinflammation in LPS-stimulated BV-2 Microglia (LPS에 의해 활성화된 미세아교세포에서 흰점박이꽃무지 에탄올 추출물의 신경염증 억제 효과)

  • Lee, Hwa Jeong;Seo, Minchul;Lee, Joon Ha;Kim, In-Woo;Kim, Sun Young;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.29 no.10
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    • pp.1096-1103
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    • 2019
  • Neuroinflammation is mediated by the activation of microglia and has been implicated in the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Therefore, the inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Protaetia brevitarsis seulensis is an insect belonging to the order Coleoptera and inhabits Korea, China, Japan and Siberia. P. brevitarsis seulensis is an edible insect that can be consumed as a protein source for humans. It has been reported that P. brevitarsis seulensis contains useful bioactive substances for hepatoprotection and improving blood circulation, such as indole alkaloids. Microglia cells are the main source of proinflammatory cytokines and nitric oxide (NO) in the central nervous system, which Perform neuroimmune, inflammatory, and other neurobilogical functions. In this study, we investigated the anti-neuroinflammatory effects of P. brevitarsis seulensis ethanol extract (PBE) in activated microglia cells treated with lipopolysaccgarude (LPS, 100 ng/ml). As a result, PBE significantly inhibited NO production without cytotoxicity and decreased the expression levels of inducible NO synthase and cyclooxygenase-2. In addition, the production of inflammatory cytokine secreted by LPS was also reduced by PBE. These results suggest that PBE could be a good source of functional substances to prevent neuroinflammation and neurodegenerative diseases.

Inhibitory Effects of Asparagus cochinchinensis in LPS-Stimulated BV-2 Microglial Cells through Regulation of Neuroinflammatory Mediators, the MAP Kinase Pathway, and the Cell Cycle (Lipopolysaccharide로 자극된 BV-2 미세교세포에서 신경염증 매개체, MAP kinase경로, 세포주기의 조절에 의한 천문동(Asparagus cochinchinensis)의 저해효과)

  • Lee, Hyun Ah;Kim, Ji Eun;Choi, Jun Young;Sung, Ji Eun;Youn, Woo Bin;Son, Hong Joo;Lee, Hee Seob;Kang, Hyun-Gu;Hwang, Dae Youn
    • Journal of Life Science
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    • v.30 no.4
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    • pp.331-342
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    • 2020
  • The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

Imaging Neuroreceptors in the Living Human Brain

  • Wagner Jr Henry N.;Dannals Robert F.;Frost J. James;Wong Dean F.;Ravert Hayden T.;Wilson Alan A.;Links Jonathan M.;Burns H. Donald;Kuhar Michael J.;Snyder Solomon H.
    • The Korean Journal of Nuclear Medicine
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    • v.18 no.2
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    • pp.17-23
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    • 1984
  • For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human mind in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On May 25, 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuro-receptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. The growth of any scientific field is based on a paradigm or set of ideas that the community of scientists accepts. The unifying principle of nuclear medicine is the tracer principle applied to the study of human disease. Nineteen hundred and sixty-three was a landmark year in which technetium-99m and the Anger camera combined to move the field from its latent stage into a second stage characterized by exponential growth within the framework of the paradigm. The third stage, characterized by gradually declining growth, began in 1973. Faced with competing advances, such as computed tomography and ultrasonography, proponents and participants in the field of nuclear medicine began to search for greener pastures or to pursue narrow sub-specialties. Research became characterized by refinements of existing techniques. In 1983 nuclear medicine experienced what could be a profound change. A new paradigm was born when it was demonstrated that, despite their extremely low chemical concentrations, in the picomolar range, it was possible to image and quantify the distribution of receptors in the human body. Thus, nuclear medicine was able to move beyond physiology into biochemistry and pharmacology. Fundamental to the science of pharmacology is the concept that many drugs and endogenous substances, such as neurotransmitters, react with specific macromolecules that mediate their pharmacologic actions. Such receptors are usually identified in the study of excised tissues, cells or cell membranes, or in autoradiographic studies in animals. The first imaging and quantification of a neuroreceptor in a living human being was performed on May 25, 1983 and reported in the September 23, 1983 issue of SCIENCE. The study involved the development and use of carbon-11 N-methyl spiperone (NMSP), a drug with a high affinity for dopamine receptors. Since then, studies of dopamine and serotonin receptors have been carried out in over 100 normal persons or patients with various neuropsychiatric disorders. Exactly one year later, the first imaging of opitate receptors in a living human being was performed [1].

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