Co-deposition of MoS2films by reactive sputtering and formation of tree-like structures.

Transition metal dichalcogenides (TMDCs) are versatile layered materials with potential applications ranging from optoelectronic devices to water splitting. Top-down fabrication methods such as exfoliation are not practical for a large-scale production of high-quality devices: a bottom-up approach such as sputtering, a low-temperature deposition method, is more suitable. However, due to its anisotropic nature, the growth mechanism of molybdenum disulfide (MoS2) via sputtering is complex and remains to be investigated in detail. In this paper, we study the growth of MoS2 films co-deposited by using a sulfur (S) hot-lip cell and a molybdenum (Mo) sputtering target via reactive sputtering. The impact of S partial pressure on the structure and morphology of MoS2films was systematically characterized, and it was observed that the growth is dominated by vertically-oriented sheets with horizontal branches, resulting in a tree-like structure. The growth front of the structures is ascribed to the anisotropic incorporation of adatoms with regards to the orientation of MoS2.

A novel role for flotillin-1 in H-Ras-regulated breast cancer aggressiveness.

Elevated expression and aberrant activation of Ras have been implicated in breast cancer aggressiveness. H-Ras, but not N-Ras, induces breast cell invasion. A crucial link between lipid rafts and H-Ras function has been suggested. This study sought to identify the lipid raft protein(s) responsible for H-Ras-induced tumorigenicity and invasiveness of breast cancer. We conducted a comparative proteomic analysis of lipid raft proteins from invasive MCF10A human breast epithelial cells engineered to express active H-Ras and non-invasive cells expressing active N-Ras. Here, we identified a lipid raft protein flotillin-1 as an important regulator of H-Ras activation and breast cell invasion. Flotillin-1 was required for epidermal growth factor-induced activation of H-Ras, but not that of N-Ras, in MDA-MB-231 triple-negative breast cancer (TNBC) cells. Flotillin-1 knockdown inhibited the invasiveness of MDA-MB-231 and Hs578T TNBC cells in vitro and in vivo. In xenograft mouse tumor models of these TNBC cell lines, we showed that flotillin-1 played a critical role in tumor growth. Using human breast cancer samples, we provided clinical evidence for the metastatic potential of flotillin-1. Membrane staining of flotillin-1 was positively correlated with metastatic spread (p = 0.013) and inversely correlated with patient disease-free survival rates (p = 0.005). Expression of flotillin-1 was associated with H-Ras in breast cancer, especially in TNBC (p < 0.001). Our findings provide insight into the molecular basis of Ras isoform-specific interplay with flotillin-1, leading to tumorigenicity and aggressiveness of breast cancer.

Identification of proteins regulated by curcumin in cerebral ischemia.

BACKGROUND: Curcumin is known to have a neuroprotective effect against cerebral ischemia. The objective of this study was to identify various proteins that are differentially expressed by curcumin treatment in focal cerebral ischemia using a proteomic approach. METHODS: Adult male rats were treated with vehicle or curcumin 1 h after middle cerebral artery occlusion. Brain tissues were collected 24 h after the onset of middle cerebral artery occlusion, and cerebral cortices proteins were identified by two-dimensional gel electrophoresis and mass spectrometry. RESULTS: We detected several proteins with altered expression levels between vehicle- and curcumin-treated animals. Among these proteins, ubiquitin carboxy-terminal hydrolase L1, isocitrate dehydrogenase, adenosylhomocysteinase, and eukaryotic initiation factor 4A were decreased in the vehicle-treated animal, and curcumin treatment attenuated the injury-induced decreases of these proteins. Conversely, pyridoxal phosphate phosphatase was increased in the vehicle-treated animal, and curcumin treatment prevented decreases in this protein. The identified altered proteins are associated with cellular metabolism and differentiation. CONCLUSIONS: The results of this study suggest that curcumin exerts a neuroprotective effect by regulating the expression of various proteins in focal cerebral ischemia.

Hedgehog signaling between cancer cells and hepatic stellate cells in promoting cholangiocarcinoma.

BACKGROUND: Aberrant Hedgehog (HH) signaling activation is important in cancer growth and mediates the interaction between cancer cells and the surrounding stromal cells. This study investigated the role of HH signaling on the growth of cholangiocarcinoma (CC), focusing on the interaction of CC cells with stromal cells. METHODS: To evaluate the interaction between human CC cells (SNU-1196, SNU-246, SNU-308, SNU-1079, and HuCCT-1) and stromal cells (hepatic stellate cell line, Lx-2), co-culture proliferation, migration, and invasion assays were performed. In vivo nude mice experiments were conducted using two groups-HuCCT-1 single implant xenograft (SX) and co-implant xenograft (CX) with HuCCT-1 and Lx-2. RESULTS: When HuCCT-1 cells were co-cultured with Lx-2 cells, the expression of HH signaling-related proteins increased in both HuCCT-1 and Lx-2 cells. Co-culture with Lx-2 cells stimulated the proliferation, migration, and invasion of CC cells, and these effects were mediated by HH signaling. Co-culture of HuCCT-1 and Lx-2 cells increased the secretion of several cytokines. In an ectopic xenograft model, Lx-2 co-implantation increased CC tumor growth and stimulated angiogenesis. Cyclopamine attenuated tumor growth in the CX group, but not in the HuCCT-1 mono-implant (SX) group. Cyclopamine treatment decreased CC cell proliferation, suppressed microvessel density, and increased tumor necrosis in the CX group, but not in the SX group. CONCLUSION: Hepatic stellate cells stimulate the proliferation, migration, and invasion of CC cells, promote angiogenesis through HH signaling activation, and render CC more susceptible to necrosis by HH inhibitor.

Quadriplegia, Dysphagia and Ataxia Manifested in a Child With COVID-19 Related Acute Necrotizing Encephalopathy: A Case Report.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, presents primarily with respiratory symptoms. However, children with COVID-19 are usually asymptomatic or mild acute symptoms and also neurological manifestations have also been observed. We report the case of a 7-year-old girl who presented with high fever and altered mental status, leading to a diagnosis of COVID-19 and acute necrotizing encephalopathy (ANE). The patient received intensive medical care in the intensive care unit and subsequently underwent rehabilitation programs due to neurological functional sequelae. Neurological complications in COVID-19, including ANE, may result from potential viral nerve involvement, cytokine storms, and the blood-brain barrier disruption. Early rehabilitation plays a pivotal role in managing COVID-19-related neurological complications and enhancing patients' functional outcomes. Further research is essential to gain a better understanding of the mechanisms and treatment strategies for neurological manifestations in pediatric COVID-19 patients, particularly those with multisystem inflammatory syndrome in child.

Heme protein identified from scaly-foot gastropod can synthesize pyrite (FeS2) nanoparticles.

The scaly-foot gastropod (Chrysomallon squamiferum), which lives in the deep-sea zone of oceans around thermal vents, has a black shell and scales on the foot. Both the black shell and scales contain iron sulfide minerals such as greigite (Fe3S4) and pyrite (FeS2). Although pyrite nanoparticles can be used as materials for solar panels, it is difficult to synthesize stable and spherical nanoparticles in vitro. In this study, we extracted organic molecules that interact with nano-pyrite from the shell of the scaly-foot gastropod to develop a low-cost, eco-friendly method for pyrite nanoparticles synthesis. Myoglobin (csMG), a heme protein, was identified in the iron sulfide layer of the shell. We purified recombinant csMG (r-csMG) and demonstrated that r-csMG helped in the conversion of ferric ions, sulfide ions and sulfur into spherical shaped pyrite nanoparticles at 80°C. To reduce the effort and cost of production, we showed that commercially available myoglobin from Equus caballus (ecMG) also induced the in vitro synthesis of pyrite nanoparticles. Using structure-function experiments with digested peptides, we highlighted that the amino acid sequence of r-csMG peptides controlled the spherical shape of the nanoparticle while the hemin molecules, which the peptides interacted with, maintained the size of nanoparticles. Synthesized pyrite nanoparticles exhibited strong photoluminescence in the visible wavelength region, suggesting its potential application as a photovoltaic solar cell material. These results suggest that materials for solar cells can be produced at low cost and energy under eco-friendly conditions. STATEMENT OF SIGNIFICANCE: Pyrite is a highly promising material for photovoltaic devices because of its excellent optical, electrical, magnetic, and transport properties and high optical absorption coefficient. Almost all current pyrite synthesis methods use organic solvents at high temperature and pressure under reducing conditions. Synthesized pyrite nanoparticles are unstable and are difficult to use in devices. The scaly-foot gastropod can synthesize pyrite nanoparticles in vivo, meaning that pyrite nanoparticles can be generated in an aqueous environment at low temperature. In this study, we demonstrated the synthesis of pyrite nanoparticles using a heme protein identified in the iron sulfide layer of the scaly-foot gastropod shell. These results exemplify how natural products in organisms can inspire the innovation of new technology.

Chlorogenic acid alleviates the reduction of Akt and Bad phosphorylation and of phospho-Bad and 14-3-3 binding in an animal model of stroke.

BACKGROUND: Stroke is caused by disruption of blood supply and results in permanent disabilities as well as death. Chlorogenic acid is a phenolic compound found in various fruits and coffee and exerts antioxidant, anti-inflammatory, and anti-apoptotic effects. OBJECTIVES: The purpose of this study was to investigate whether chlorogenic acid regulates the PI3K-Akt-Bad signaling pathway in middle cerebral artery occlusion (MCAO)-induced damage. METHODS: Chlorogenic acid (30 mg/kg) or vehicle was administered peritoneally to adult male rats 2 h after MCAO surgery, and animals were sacrificed 24 h after MCAO surgery. Neurobehavioral tests were performed, and brain tissues were isolated. The cerebral cortex was collected for Western blot and immunoprecipitation analyses. RESULTS: MCAO damage caused severe neurobehavioral disorders and chlorogenic acid improved the neurological disorders. Chlorogenic acid alleviated the MCAO-induced histopathological changes and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Furthermore, MCAO-induced damage reduced the expression of phospho-PDK1, phospho-Akt, and phospho-Bad, which was alleviated with administration of chlorogenic acid. The interaction between phospho-Bad and 14-3-3 levels was reduced in MCAO animals, which was attenuated by chlorogenic acid treatment. In addition, chlorogenic acid alleviated the increase of cytochrome c and caspase-3 expression caused by MCAO damage. CONCLUSIONS: The results of the present study showed that chlorogenic acid activates phospho-Akt and phospho-Bad and promotes the interaction between phospho-Bad and 14-3-3 during MCAO damage. In conclusion, chlorogenic acid exerts neuroprotective effects by activating the Akt-Bad signaling pathway and maintaining the interaction between phospho-Bad and 14-3-3 in ischemic stroke model.

Chlorogenic acid alleviates cerebral ischemia-induced neuroinflammation via attenuating nuclear factor kappa B activation.

Ischemic stroke is the most common type of stroke and is caused by vascular closure. Chlorogenic acid is a polyphenolic compound that is present in various plants. It is used as a traditional oriental medicine because of its anti-oxidant and anti-inflammatory properties. We investigated whether chlorogenic acid mediates neuroprotective effects by regulating pro-inflammatory proteins. Focal cerebral ischemia was induced through middle cerebral artery occlusion (MCAO) surgery in adult rats. Chlorogenic acid (30 mg/kg) or vehicle was injected into the abdominal cavity 2 h after MCAO. Rats were sacrificed 24 h after MCAO surgery and brain tissues were isolated immediately. MCAO caused histopathological changes in the ischemic cerebral cortex, and chlorogenic acid attenuated these changes. Chlorogenic acid reduced MCAO-induced reactive oxygen species generation and oxidative stress increase in the cerebral cortex. Furthermore, cerebral ischemia increased the expression of ionized calcium-binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP), which are microglia and astrocyte activation markers, respectively. However, chlorogenic acid prevented MCAO-induced these increases. MCAO damage also increased the expression of nuclear factor-κB (NF-κB), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). Chlorogenic acid treatment attenuated these increases caused by MCAO. These proteins are representative pro-inflammatory markers. This study confirmed that chlorogenic acid exerts an anti-oxidative effect and elucidated anti-inflammatory effect through regulating NF-κB, IL-1ß, and TNF-α on cerebral ischemia. Thus, we can suggest that chlorogenic acid has neuroprotective effects by reducing oxidative stress and controlling pro-inflammatory proteins against cerebral ischemic damage.

Anti-obesity Effects of Dark Tea Extracts by Down-regulation of C/EBPα and PPARγ.

BACKGROUND/AIM: Dark tea, made by fermentation of tea leaves using microorganisms, is well known for its antiobesity effect; however, studies to identify this effect have not been sufficiently conducted. Herein, the anti-obesity effects of post-fermented dark tea were studied in high-fat diet mouse. MATERIALS AND METHODS: Obesity was induced through a high-fat diet in C57BL/6 mice, and then dark tea extract powder (DTP) was orally administered daily for 12 weeks to evaluate the body and organ weights. Changes in the biochemical markers of obesity were evaluated to study the mechanism of the anti-obesity effects of DTP. RESULTS: When DTP was administered to obesity mice, the weight and food intake reduced, blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) decreased, whereas high-density lipoprotein cholesterol (HDL-C) increased. Histopathology showed that steatosis and inflammation scores were reduced within the liver and adipocyte sizes were reduced within epididymal adipocyte. In addition, a significant decrease in blood insulin and hepatic TG and a significant increase in blood adiponectin were also confirmed. The results of western blot and qPCR in week 12, showed a significant decrease in the mRNA and protein levels of C/EBPα, and the mRNA levels of PPARγ in the liver. CONCLUSION: Dark tea extracts are thought to have an anti-obesity effect by reducing the levels of the main transcription factors that promote adipocyte differentiation, such as C/EBPα, and PPARγ. Therefore, diet products using dark tea extracts could be developed.

Proteomic analysis of placentas from cloned cat embryos identifies a set of differentially expressed proteins related to oxidative damage, senescence and apoptosis.

Production of cloned mammals by somatic cell nuclear transfer is associated with functional and structural abnormalities of placentation and with abnormal fetal development. A proteomic analysis was performed in domestic cats (Felis catus) to compare cloned term placentas (CTP) obtained from cesarean section (CS) to control placentas obtained from CS or vaginal delivery. The expression of 20 proteins was altered in CTP (p<0.05) compared to control placentas. The two control groups showed that the method of delivery, vaginal delivery or CS, did not affect protein expression (p>0.05). A total of 13 proteins were up-regulated in CTP, including apoptosis-related cathepsin D (CD), annexin A1 and heat shock protein 27 (HSP 27), and seven proteins were down-regulated in CTP, including prohibitin (PHB). The expression of PHB and CD was confirmed by Western blotting and immunofluorescence staining. The abnormal expression of PHB and CD correlated with the generation of reactive oxygen species, leading to decreased mitochondrial membrane potential and telomeric DNA, which are associated with cellular senescence and apoptosis. In summary, a specific pattern of abnormal protein expression is associated with the impaired development and functions of cloned placentas and hence with decreased fetal viability. Strategies aimed at restoring normal placental protein expression may increase the efficiency of somatic cell nuclear transfer and transgenic cat production and help restore endangered species.

Chlorogenic acid alleviates neurobehavioral disorders and brain damage in focal ischemia animal models.

Cerebral ischemia leads to neuronal cell death, causes neurological disorder and permanent disability. Chlorogenic acid has antioxidant, anti-inflammatory, and anti-apoptotic properties. This study investigated the neuroprotective effects of chlorogenic acid against cerebral ischemia. Focal cerebral ischemia was induced in male adult rats via middle cerebral artery occlusion (MCAO). Chlorogenic acid (30 mg/kg) or vehicle was injected in the intraperitoneal cavity 2 h after MCAO operation. Neurological behavior tests were performed 24 h after MCAO, brain edema and infarction were measured. Oxidative stress was assessed by investigating the levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) levels. MCAO damage leaded to severe neurobehavioral deficits, increased ROS and LPO levels, and induced brain edema and infarction. MCAO damage caused histopathological damages and increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the cerebral cortex. However, chlorogenic acid treatment improved neurological behavioral deficits caused by MCAO and attenuated the increase in ROS and LPO levels. It also alleviated MCAO-induced brain edema, infarction, and histopathological lesion. Chlorogenic acid treatment attenuated the increase in the number of TUNEL-positive cells in the cerebral cortex of MCAO animals. We also investigated caspase proteins expression to elucidate the neuroprotective mechanism of chlorogenic acid. Caspase-3, caspase-7, and poly ADP-ribose polymerase expression levels were increased in the MCAO damaged cortex, while chlorogenic acid mitigated these increases. These results showed that MCAO injury leads to severe neurological damages and chlorogenic acid exerts neuroprotective effects by regulating oxidative stress and caspase proteins expressions. Thus, our findings suggest that chlorogenic acid acts as a potent neuroprotective agent by modulating the apoptotic-related proteins.

Alpha-Linolenic Acid Impedes Cadmium-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration in Mouse Brain.

Alpha-Linolenic acid (ALA), an omega-3 polyunsaturated fatty acid, is extracted from plant sources and has been shown to be one of the anti-inflammatory and antioxidant agents. Herein, we revealed the molecular mechanism underlying the anti-inflammatory and antioxidant potential of (ALA), against cadmium in the adult mouse brain. We evaluated the neuroprotective effect of ALA (60 mg/kg per oral for 6 weeks) against CdCl2 (5 mg/kg)-induced oxidative stress, neuroinflammation, and neuronal apoptosis. According to our findings, ALA markedly reduced ROS production and nitric oxide synthase 2 (NOS2) and enhanced the expression of nuclear factor-2 erythroid-2 (Nrf-2) and heme oxygenase-1 (HO-1) in mice treated with CdCl2. Most importantly, the molecular docking study revealed that ALA allosterically decreases the overexpression of c-Jun N-terminal kinase (JNK) activity and inhibited the detrimental effect against CdCl2. Moreover, ALA suppressed CdCl2-induced glial fibrillary acidic protein (GFAP), nuclear factor-kappa b (NF-κB), and interleukin-1ß (IL-1ß) in the mouse brain. Further, we also checked the pro- and anti-apoptotic proteins markers such as Bax, Bcl-2, and caspase-3, which were regulated in the cortex of ALA co-treated mouse brain. Overall, our study suggests that oral administration of ALA can impede oxidative stress, neuroinflammation, and increase neuronal apoptosis in the cortex of Cd-injected mouse brain.

Melanogenesis inhibitory effect of fatty acid alkyl esters isolated from Oxalis triangularis.

Ten fatty acid alkyl esters isolated from Oxalis triangularis, were evaluated for the effects on melanogenesis using mouse B16 melanoma cells. Treatment of methyl linoleate, methyl linolenate, ethyl linoleate and ethyl linolenate significantly blocked forskolin-induced melanogenesis and inhibited tyrosinase activity. In addition, we found that they inhibited cAMP production, suggesting that their anti-melanogenic effect is mediated by the inhibition of cAMP production. We concluded that methyl/ethyl linoleate and linolenate isolated from Oxalis triangularis have pigment inhibition activity. These compounds may be useful as the cosmetic agent to stimulate skin whitening.

Injury of Corticospinal Tract in a Patient with Subarachnoid Hemorrhage as Determined by Diffusion Tensor Tractography: A Case Report.

We report diffusion tensor tractography (DTT) of the corticospinal tract (CST) in a patient with paresis of all four limbs following subarachnoid hemorrhage (SAH) with intraventricular hemorrhage (IVH) after the rupture of an anterior communicating artery (ACoA) aneurysm rupture. The 73-year-old female was admitted to our emergency room in a semi-comatose mental state. After coil embolization-an acute SAH treatment-she was transferred to our rehabilitation department with motor weakness development, two weeks after SAH. Upon admission, she was alert but she complained of motor weakness (upper limbs: MRC 3/5, and lower limbs: MRC 1/5). Four weeks after onset, DTT showed that the bilateral CSTs failed to reach the cerebral cortex. The left CST demonstrated a wide spread of fibers within the corona radiata as well as significantly lower tract volume (TV) and higher fractional anisotropy (FA) as well as mean diffusivity (MD) compared to the controls. On the other hand, the right CST shifted to the posterior region at the corona radiata, and MD values of the right CST were significantly higher when compared to the controls. Changes in both CSTs were attributed to vasogenic edema and compression caused by untreated hydrocephalus. We demonstrate in this case, two different pathophysiological entitles, contributing to this patient's motor weakness after SAH.

The combined effect of granulocyte-colony stimulating factor (G-CSF) treatment and exercise in rats with spinal cord injury.

Objective: To identify that the combined G-CSF and treadmill exercise is more effective in functional recovery after spinal cord injury (SCI).Design: Rats were divided into 4 groups: a SCI group treated with G-CSF (G-CSF group, n = 6), a SCI group treated with treadmill exercise plus G-CSF (G-CSF/exercise group, n = 6), a SCI group with treadmill exercise (exercise group, n = 6), and a SCI group without treatments (control group, n = 6). We performed laminectomy at the T8-10 spinal levels with compression injury of the spinal cord in all rats. G-CSF (20 µg/ml) was administered intraperitoneally for 5 consecutive days after SCI in G-CSF and G-CSF/exercise groups. From one week after surgery, animals in G-CSF/exercise and exercise groups received 30 min of exercise 5 days per week for 4 weeks. Functional recoveries were assessed using the Basso, Beattie, and Bresnahan (BBB) scale and the inclined plane test. Five weeks after SCI, hematoxylin and eosin staining for cavity size and immunohistochemistry for glial scar formation and neuro-regeneration factor expression were conducted.Setting: Inha University School of medicine, Incheon, KoreaResults: Rats in G-CSF/exercise group showed the most effective functional recovery in the BBB scale and the inclined plane test, and spinal cord cavity size by injury were the smallest, and immunohistochemistry revealed expression of higher BDNF (brain-derived neurotrophic factor) and VEGF (vascular endothelial growth factor) and lower GFAP (glial fibrillary acidic protein) than others.Conclusion: Combined treatment provided more effective neuroplasty and functional recovery than individual treatments.

Baicalin alleviates lipopolysaccharide-induced neuroglial activation and inflammatory factors activation in hippocampus of adult mice.

Baicalin is a natural flavonoid that exerts a variety of pharmaceutical effects such as anti-inflammatory and antioxidant. Lipopolysaccharide (LPS) is an endotoxin that releases inflammatory cytokines and induces inflammatory response. This study was investigated the anti-inflammatory mechanism of baicalin against LPS-induced inflammatory response in the hippocampus. Adult mice were randomly grouped into control, LPS-treated, and LPS and baicalin co-treated animals. LPS (250 µg/kg/day) and baicalin (10 mg/kg/day) were administered intraperitoneally for 7 consecutive days. We measured neuroglia cells activation and inflammatory factors activation using Western blot analysis and immunofluorescence staining techniques. Ionized calcium binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) are widely used as microglia and astrocyte markers, respectively. LPS treatment increased Iba-1 and GFAP expression, while baicalin co-treatment attenuated this overexpression. Nuclear factor-kappa B (NF-κB) is a key mediator of inflammation. Baicalin co-treatment alleviated LPS-induced increase of NF-κB in the hippocampus. In addition, LPS treatment upregulated pro-inflammatory cytokines including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). However, baicalin co-treatment prevented LPS-induced increases of IL-1ß and TNF-α in the hippocampus. Results from the present study showed that baicalin suppresses LPS-induced neuroinflammation by regulating microglia and astrocyte activation and modulating inflammatory factors in the hippocampus. Thus, these results demonstrate that baicalin has neuroprotective effect by alleviates microglia and astrocyte activation and modulates inflammatory response by suppressing NF-κB expression in hippocampus with neuroinflammation caused by LPS.

Intrastriatal grafts of mesenchymal stem cells in adult intact rats can elevate tyrosine hydroxylase expression and dopamine levels.

MSCs (mesenchymal stem cells) derived from the bone marrow have shown to be a promising source of stem cells in a therapeutic strategy of neurodegenerative disorder. Also, MSCs can enhance the TH (tyrosine hydroxylase) expression and DA (dopamine) content in catecholaminergic cells by in vitro co-culture system. In the present study, we investigated the effect of intrastriatal grafts of MSCs on TH protein and gene levels and DA content in adult intact rats. When MSCs were transplanted into the striatum of normal rats, the grafted striatum not only had significantly higher TH protein and mRNA levels, but also significantly higher DA content than the untransplanted striatum. Meanwhile, the grafted MSCs differentiated into neurons, astrocytes and oligodendrocytes; however, TH-positive cells could not be detected in our study. These experimental results offer further evidence that MSCs are a promising candidate for treating neurodegenerative diseases such as Parkinson's disease.

Identification of proteins differentially expressed by melatonin treatment in cerebral ischemic injury--a proteomics approach.

We previously reported that melatonin protects neuronal cells against ischemic brain damage. In this study, we identified proteins that were differentially expressed by melatonin treatment during ischemic brain injury. Rats were subjected to cerebral ischemia by middle cerebral artery occlusion (MCAO). Adult male rats were treated with melatonin (5 mg/kg) or vehicle prior to MCAO and brains were collected at 24 hr after MCAO. Proteins derived from the cerebral cortex were analyzed using two-dimensional gel electrophoresis. Protein spots with a greater than 2.5-fold change in intensity were identified by mass spectrometry. Among these proteins, gamma-enolase, stathmin, thioredoxin, peroxiredoxin-6, hippocalcin, protein phosphatase 2A, adenosylhomocysteinase, ubiquitin carboxy-terminal hydrolase L1, and NAD-specific isocitrate dehydrogenase subunit alpha were significantly decreased in the vehicle-treated group in comparison to the melatonin-treated group. The identified proteins consist of cell differentiation and stabilization proteins, as well as an antioxidant enzyme. In contrast, dehydroprimidinase-related protein 2 (DRP-2), a target of protein oxidation in neurodegeneration, was significantly increased in vehicle-treated animals, while melatonin prevented the injury-induced increase of DRP-2. Thus, the results of this study suggest that melatonin prevents cell death resulting from ischemic brain injury and that its neuroprotective effects are mediated by both the up- and down-regulation of various proteins.

Korean Academy of Medical Sciences Pediatric Impairment Guideline for brain lesion.

The permanent impairment evaluation for children in developmental stage is very difficult and it is even impossible in some cases. The impairment evaluation for developing children has not yet been included in the guideline of the American Medical Association. Due to frequent medical and social demands in Korea, we developed an impairment evaluation guideline for motor impairment, intellectual disability/mental retardation, developmental speech-language disorder and epilepsy caused by pediatric cerebral injuries, or cerebral lesions other than the developmental disorders such as autism. With the help of various literature and foreign institutions, we developed our in order to develop a scientific guideline for pediatric impairment that is suited to Korean cultural background and social condition.