• Parasites, Hosts and Diseases
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• 제57권3호
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• pp.291-294
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• 2019

Primary amebic encephalitis (PAM) is a devastating central nervous system infection caused by Naegleria fowleri, a free-living amoeba, which can survive in soil and warm fresh water. Here, a 43-year-old healthy male was exposed to warm freshwater 5 days before the symptom onset. He rapidly developed severe cerebral edema before the diagnosis of PAM and was treated with intravenous conventional amphotericin B while died of terminal cerebral hernia finally. Comparing the patients with PAM who has similar clinical symptoms to those with other common types of meningoencephalitis, this infection is probably curable if treated early and aggressively. PAM should be considered in the differential diagnosis of purulent meningoencephalitis, especially in patients with recent freshwater-related activities during the hot season.

• Journal of Chest Surgery
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• 제51권6호
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• pp.410-414
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• 2018

Primary pulmonary meningioma is a rare disease, and chordoid meningioma is an uncommon variant of meningioma in the central nervous system (CNS) with a high recurrence rate. We report a case of primary pulmonary chordoid meningioma that presented as a solitary pulmonary nodule (SPN). The SPN was resected by thoracoscopic wedge resection and was revealed to have characteristics of chordoid meningioma. After confirming the absence of a meningioma in the CNS by brain imaging, the nodule was diagnosed as a primary pulmonary chordoid meningioma. The patient remained disease-free after 26 months postoperatively. To our knowledge, this is the third case of primary pulmonary chordoid meningioma to be reported.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.152-159
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• 2019

Multiple sclerosis (MS) is an autoimmune disease characterized by progressive neuronal loss, neuroinflammation, axonal degeneration, and demyelination. Previous studies have reported that 6-shogaol, a major constituent of ginger (Zingiber officinale rhizome), and its biological metabolite, 6-paradol, have anti-inflammatory and anti-oxidative properties in the central nervous system (CNS). In the present study, we investigated whether 6-shogaol and 6-paradol could ameliorate against experimental autoimmune encephalomyelitis (EAE), a mouse model of MS elicited by myelin oligodendrocyte glycoprotein ($MOG_{35-55}$) peptide immunization with injection of pertussis toxin. Once-daily administration of 6-shogaol and 6-paradol (5 mg/kg/day, p.o.) to symptomatic EAE mice significantly alleviated clinical signs of the disease along with remyelination and reduced cell accumulation in the white matter of spinal cord. Administration of 6-shogaol and 6-paradol into EAE mice markedly reduced astrogliosis and microglial activation as key features of immune responses inside the CNS. Furthermore, administration of these two molecules significantly suppressed expression level of tumor necrosis $factor-{\alpha}$, a major proinflammatory cytokine, in EAE spinal cord. Collectively, these results demonstrate therapeutic efficacy of 6-shogaol or 6-paradol for EAE by reducing neuroinflammatory responses, further indicating the therapeutic potential of these two active ingredients of ginger for MS.

• 통합자연과학논문집
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• 제13권4호
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• pp.170-180
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• 2020

Abnormal regulation, hyperphosphorylation, and aggregation of the tau protein are the hallmark of several types of dementia, including Alzheimer's Disease. Increased activity of Glycogen Synthase Kinase-3β (GSK-3β) in the Central Nervous System (CNS), increased the tau hyperphosphorylation and caused the neurofibrillary tangles (NFTs) formation in the brain cells. Over the last two decades, numerous adenosine triphosphate (ATP) competitive inhibitors have been discovered that show inhibitory activity against GSK-3β. But these compounds exhibited off-target effects which motivated researchers to find new GSK-3β inhibitors. In the present study, we have collected the dataset of 31 C-Glycosylflavones derivatives that showed inhibitory activity against GSK-3β. Among the dataset, the most active compound was docked with the GSK-3β and molecular dynamics (MD) simulation was performed for 50 ns. Based on the 50 ns MD pose of the most active compound, the other dataset compounds were sketched, minimized, and aligned. The 3D-QSAR based Comparative Molecular Field Analysis (CoMFA) model was developed, which showed a reasonable value of q2=0.664 and r2=0.920. The contour maps generated based on the CoMFA model elaborated on the favorable substitutions at the R2 position. This study could assist in the future development of new GSK-3β inhibitors.

• Genomics & Informatics
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• 제20권2호
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• pp.24.1-24.8
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• 2022

Hypomyelinating leukodystrophy type 2 (HLD2), is an inherited genetic disease of the central nervous system caused by recessive mutations in the gap junction protein gamma 2 (GJC2/GJA12). HLD2 is characterized by nystagmus, developmental delay, motor impairments, ataxia, severe speech problem, and hypomyelination in the brain. The GJC2 sequence encodes connexin 47 protein (Cx47). Connexins are a group of membrane proteins that oligomerize to construct gap junctions protein. In the present study, a novel missense mutation gene c.760G>A (p.Val254Met) was identified in a patient with HLD2 by performing whole exome sequencing. Following the discovery of the new mutation in the proband, we used Sanger sequencing to analyze his affected sibling and parents. Sanger sequencing verified homozygosity of the mutation in the proband and his affected sibling. The autosomal recessive inheritance pattern was confirmed since Sanger sequencing revealed both healthy parents were heterozygous for the mutation. PolyPhen2, SIFT, PROVEAN, and CADD were used to evaluate the function prediction scores of detected mutations. Cx47 is essential for oligodendrocyte function, including adequate myelination and myelin maintenance in humans. Novel mutation p.Val254Met is located in the second extracellular domain of Cx47, both extracellular loops are highly conserved and probably induce intramolecular disulfide interactions. This novel mutation in the Cx47 gene causes oligodendrocyte dysfunction and HLD2 disorder.

• 통합자연과학논문집
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• 제15권4호
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• pp.179-186
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• 2022

The c-Jun N-terminal kinase (JNK3) play major role in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, cerebral ischemia and other Central Nervous System disorders. Since JNK3 is primarily stated in the brain and stimulated by stress-stimuli, this situation is conceivable that inhibiting JNK3 could be a possible treatment for the mechanisms underlying neurodegenerative diseases. In this study drugs from Zinc15 database were screened to identify the JNK3 inhibitors by Molecular docking and Density functional theory approach. Molecular docking was done by Autodock vina and the ligands were selected based on the binding affinity. Our results identified top ten novel ligands as potential inhibitors against JNK3. Molecular docking revealed that Venetoclax, Fosaprepitant and Avapritinib exhibited better binding affinity and interacting with proposed binding site residues of JNK3. Density functional theory was used to compute the values for energy gap, lowest unoccupied molecular orbital (LUMO), and highest occupied molecular orbital (HOMO). The results of Density functional theory study showed that Venetoclax, Fosaprepitant and Avapritinib serves as a lead compound for the development of JNK3 small molecule inhibitors.

• Korean Journal of Radiology
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• 제22권8호
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• pp.1379-1396
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• 2021

Rare neurovascular diseases (RNVDs) have not been well-recognized in Korea. They involve the central nervous system and greatly affect the patients' lives. However, these diseases are difficult to diagnose and treat due to their rarity and incurability. We established a list of RNVDs by referring to the previous literature and databases worldwide to better understand the diseases and their current management status. We categorized 68 RNVDs based on their pathophysiology and clinical manifestations and estimated the prevalence of each disease in Korea. Recent advances in genetic, molecular, and developmental research have enabled further understanding of these RNVDs. Herein, we review each disease, while considering its classification based on updated pathologic mechanisms, and discuss the management status of RNVD in Korea.

• 대한영상의학회지
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• 제83권3호
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• pp.527-537
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• 2022

철은 중추신경계 및 인체에 필수적인 성분으로 노화 및 다양한 퇴행성 뇌질환에서 뇌의 철 침착이 증가된다. 철은 MRI에서 독특한 특성을 가지고 있어 인체의 철 침착과 분포를 비침 습적으로 평가 및 정량화가 가능하다. 이 종설에서는 철 영상을 위한 MRI 기법에 대하여 알아보고, 노화 및 알츠하이머병을 포함한 퇴행성 뇌질환에서 변화를 고찰해 보고자 한다. 또한 현재 접근법의 제한점과 앞으로 기대되는 새로운 접근도 확인해 보고자 한다.

• 동의신경정신과학회지
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• 제9궈1호
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• pp.73-82
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• 1998

Substantial evidence has accumulated that Alzheimer's disease is associated with a local inflammatory reaction in senile plaques which may be immunemediated, and includes extensive Brain Neuroglial invasion, lymphocytic infiltration, cytokine deposition. Tumor necrosis factor a (TNF-a) is a cytokine which plays an important immunoenhancing role in the local acute and chronic inflammatory response in response to a variety of stimuli. The neuropeptide, substance P, can stimulate secretion of TNF-a from Brain Neuroglial cells. Neuroglia have substance P receptors in the central nervous system. WQ investigated whether RADIX ASPARAGI inhibits secretion of TNF-a from primary cultures of Brain Neuroglial cells containing both astrocyte (∼90%) and microglia (∼10%). RADIX ASPARAGI dose-dependently inhibited the TNF-a secretion induced by substance P plus lipopolysaccharide (LPS). In cultures enriched for micoglia (>95% pure). LPS stimulated the secretion of TNF-a but substance P caused no enhancement. Because there was no synergism between substance P and LPS in the microglial cultures it is resonable to substance P madiated enhancement of TNF-a secretion. IL-1 is a modulator of TNF-a secretion in the immune system. Also IL-1 has been shown to elevate TNF- a secretion from LPS-stimulated Brain Neuroglial cells while having no effect on Brain Neuroglial cells in the absence of LPS. We therfore investigated whether IL-1 mediates the RADIX ASPARAGI inhibition of TNF-a secretion form primary Brain Neuroglial cells. Treatment of RADIX ASPARAGI to mixed cultures stimulated with both substance P and LPS decreased TNF-a secretion to the level observed with LPS alone. These results indicate that RADIX ASPARAGI possess strong antiinflammatory activity in the cental nervous system by inhibition of inflammatory cytokines secretion from Brain Neuroglial cells.

• Clinical and Experimental Pediatrics
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• 제56권7호
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• pp.271-274
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• 2013

Brain insults, including neurotrauma, infection, and perinatal injuries such as hypoxic ischemic encephalopathy, generate inflammation in the brain. These inflammatory cascades induce a wide spectrum of cytokines, which can cause neuron degeneration, have neurotoxic effects on brain tissue, and lead to the development of seizures, even if they are subclinical and occur at birth. Cytokines are secreted by the glial cells of the central nervous system and they function as immune system mediators. Cytokines can be proinflammatory or anti-inflammatory. Interleukin (IL)-$1{\beta}$ and IL-8 are proinflammatory cytokines that activate additional cytokine cascades and increase seizure susceptibility and organ damage, whereas IL-1 receptor antagonist and IL-10 act as anti-inflammatory cytokines that have protective and anticonvulsant effects. Therefore, the immune system and its associated inflammatory reactions appear to play an important role in brain damage. Whether cytokine release is relevant for the processes of epileptogenesis and antiepileptogenesis, and whether epileptogenesis could be prevented by immunomodulatory treatment should be addressed in future clinical studies. Furthermore, early detection of brain damage and early intervention are essential for the prevention of disease progression and further neurological complications. Therefore, cytokines might be useful as biomarkers for earlier detection of brain damage in high-risk infants.