Hydroethanolic extract of Cirsium setidens ameliorates doxorubicin-induced cardiotoxicity by AMPK-PGC-1α-SOD-mediated mitochondrial protection.

BACKGROUND: Doxorubicin (DOX) is an effective anticancer agent. However, the clinical outcomes of DOX-based therapies are severely hampered by their significant cardiotoxicity. PURPOSE: We investigated the beneficial effects of an ethanol extract of Cirsium setidens (CSE) on DOX-induced cardiomyotoxicity (DICT). METHODS: UPLC-TQ/MS analysis was used to identify CSE metabolite profiles. H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells were used to evaluate the effects of CSE on DICT-induced cell death. To elucidate the mechanism underlying it, AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma co-activator l-alpha (PGC1-α), nuclear respiratory factor 1 (NRF1), NRF2, superoxide dismutase (SOD1), and SOD2 expression was detected using western blot analysis. The oxygen consumption rate (OCR), cellular ROS, and mitochondrial membrane potential were measured. Finally, we confirmed the cardioprotective effect of CSE against DICT in both C57BL/6 mice and human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) by observing various parameters, such as electrophysiological changes, cardiac fibrosis, and cardiac cell death. RESULTS: Chlorogenic acid and nicotiflorin were the major compounds in CSE. Our data demonstrated that CSE blocked DOX-induced cell death of H9c2 cells without hindrance of its apoptotic effects on MDA-MB-231 cells. DOX-induced defects of OCR and mitochondrial membrane potential were recovered in a CSE through upregulation of the AMPK-PGC1-α-NRF1 signaling pathway. CSE accelerated NRF1 translocation to the nucleus, increased SOD activity, and consequently blocked apoptosis in H9c2 cells. In mice treated with 400 mg/kg CSE for 4 weeks, electrocardiogram data, creatine kinase and lactate dehydrogenase levels in the serum, and cardiac fibrosis, were improved. Moreover, various electrophysiological features indicative of cardiac function were significantly enhanced following the CSE treatment of hiPSCCMs. CONCLUSION: Our findings demonstrate CSE that ameliorates DICT by protecting mitochondrial dysfunction via the AMP- PGC1α-NRF1 axis, underscoring the therapeutic potential of CSE and its underlying molecular pathways, setting the stage for future investigations into its clinical applications.

Gamma-Aminobutyric Acid in Rice Bran Extract Exerts Antistress Effects in Mouse Models with Depressive-Like Behaviors.

Various neurotransmitters are involved in regulating stress systems. In this study, we investigated the effects of gamma-aminobutyric acid-rich rice bran extract (GRBe) in mice stressed by forced swimming and tail suspension tests. Four weeks of oral administration of GRBe (500-2000 mg/kg) reduced the levels of dopamine and corticosterone in the blood and brain while increasing serotonin levels. GRBe was involved not only in stress but also in regulating sleep and obesity-related genes. Modern society experiences diverse and tense lives because of urbanization and informatization, which cause excessive stress due to complicated interpersonal relationships, heavy work burden, and fatigue from the organized society. High levels of stress cause psychological instability and disrupt the balance in the autonomic nervous system, which maintains the body's equilibrium, resulting in cardiovascular and cerebrovascular diseases, hormonal imbalances, and sleep disorders. Therefore, our results suggest that GRBe is a useful substance that can relieve tension by ultimately influencing a depressive-like state by lowering the levels of neuronal substances, hormones, and cytokines involved in stress and sleep disorders.

Basic Fibroblast Growth Factor Induces Cholinergic Differentiation of Tonsil-Derived Mesenchymal Stem Cells.

BACKGROUND: Mesenchymal stem cells (MSCs) are considered a potential tool for regenerating damaged tissues due to their great multipotency into various cell types. Here, we attempted to find the appropriate conditions for neuronal differentiation of tonsil-derived MSCs (TMSCs) and expand the potential application of TMSCs for treating neurological diseases. METHODS: The TMSCs were differentiated in DMEM/F-12 (Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12) supplemented with various neurotrophic factors for 7-28 days to determine the optimal neuronal differentiation condition for the TMSCs. The morphologies as well as the levels of the neural markers and neurotransmitters were assessed to determine neuronal differentiation potentials and the neuronal lineages of the differentiated TMSCs. RESULTS: Our initial study demonstrated that DMEM/F12 supplemented with 50 ng/mL basic fibroblast growth factor with 10 µM forskolin was the optimal condition for neuronal differentiation for the TMSCs. TMSCs had higher protein expression of neuronal markers, including neuron-specific enolase (NSE), GAP43, postsynaptic density protein 95 (PSD95), and synaptosomal-associated protein of 25 kDa (SNAP25) compared to the undifferentiated TMSCs. Immunofluorescence staining also validated the increased mature neuron markers, NeuN and synaptophysin, in the differentiated TMSCs. The expression of glial fibrillar acidic protein and ionized calcium-binding adaptor molecule 1 the markers of astrocytes and microglia, were also slightly increased. Additionally, the differentiated TMSCs released a significantly higher level of acetylcholine, the cholinergic neurotransmitter, as analyzed by the liquid chromatography-tandem mass spectrometry and showed an enhanced choline acetyltransferase immunoreactivity compared to the undifferentiated cells. CONCLUSION: Our study suggests that the optimized condition favors the TMSCs to differentiate into cholinergic neuron-like phenotype, which could be used as a possible therapeutic tool in treating certain neurological disorders such as Alzheimer's disease.

Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms. Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor ß (TGF-ß) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-ß expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.

In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice.

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg-1∙d-1 had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg-1∙d-1. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.

Lipidomics reveals that acupuncture modulates the lipid metabolism and inflammatory interaction in a mouse model of depression.

Depression is a serious disease that has considerable impact on lipid metabolism and inflammatory responses. Recent studies have shown that leptin, which is well known as a mediator of energy homeostasis and is a cytokine in inflammatory response, plays an important role in depression. Acupuncture is widely used to treat depression; however, the underlying mechanisms and the effect of acupuncture on depression remain poorly understood. In this study, we utilized the chronic restraint stress (CRS) induced depression model and acupuncture treatment was performed at KI10, LR8, LU8, LR4 (AP) or non-acupoint (NP). Then, lipidomics was applied to investigate the effects of acupuncture on lipid metabolism and analyze leptin signals in the brain and changes of immune markers. Acupuncture treatment at AP improved depression-like behavior in an open-field test, forced swimming test, and marble burying test. Concurrently, CRS mice treated with AP acupuncture (CRS + AP) had significantly lower levels of aspartate aminotransaminase (AST, liver injury markers) and exhibited different lipid patterns in liver lipidomic profiles. In particular, triglycerides (TGs) contributed the change of lipid patterns. Compared to the CRS mice, TGs with relatively high degrees of unsaturated fatty acids increased in the CRS + AP mice, but did not change in CRS mice treated with NP acupuncture (CRS + NP). The levels of leptin in plasma and leptin receptor positive cells in the brain (hypothalamus and hippocampus) decreased and increased, respectively, in the CRS + AP mice, while opposite patterns were exhibited in the CRS and CRS + NP mice. These results indicated that acupuncture treatment at AP attenuated leptin insensitivity in CRS mice. Additionally, expression of pro-inflammatory cytokines such as interleukin-1 beta and tumor necrosis factor-alpha were decreased in the spleen, plasma, and liver of CRS + AP mice, which was one of results of alleviation of leptin resistance. In conclusion, these results show that AP acupuncture treatment effectively alleviated the depression-like behavior, affected immune responses, and altered hepatic lipid metabolism through the attenuation of leptin insensitivity.

Dendropanax morbifera Branch Water Extract Increases the Immunostimulatory Activity of RAW264.7 Macrophages and Primary Mouse Splenocytes.

Polyacetylenes in the bark of Dendropanax morbifera trees have been reported to promote immune cell proliferation and to strengthen the innate immune system. The immunomodulatory potential of D. morbifera branch water extract (DBW) was evaluated by determining its effect on cell viability and the expression of cytokines and immune effector molecules in mouse RAW264.7 macrophages and splenocytes. Production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (interleukin [IL]-1ß, IL-2, and IFN-γ) in RAW264.7 macrophages increased after treatment with DBW. The activation of components of the NF-κB signaling pathway, including the phospho-IκBα and the expression and translocation of p65, a subunit of NF-κB, were also increased in RAW264.7 mouse macrophage cells after treatment with DBW. In addition, when mice were orally administered DBW, splenocyte cytokines and NO production were increased in a dose-dependent manner relative to control-treated mice. Furthermore, natural killer cell activity in DBW-treated mice was determined by lactate dehydrogenase (LDH) release assay. LDH release also increased in response to DBW treatment. Taken together, these results indicate that D. morbifera extract enhances innate immunity by promoting NF-κB signaling, leading to increased expression of proinflammatory cytokines and effector molecules. DBW therefore has potential therapeutic use in the context of immune stimulation.

Antiobesity and Cholesterol-Lowering Effects of Dendropanax morbifera Water Extracts in Mouse 3T3-L1 Cells.

Obesity is the most common metabolic disease in developed countries and has become a global epidemic in recent years. Obesity is associated with various metabolic abnormalities, including glucose intolerance, insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Leaves from the plant Dendropanax morbiferus are beneficial to health as they contain high levels of vitamin C and tannin. There have been seminal studies on the anticancer, antimicrobial, antidiabetes, and antihyperglycemic effects of treatments with D. morbiferus trees. Herein, we investigated the toxicity of D. morbiferus water (DLW) extracts in vitro, and demonstrated no toxicity at 5-500 µg/mL in 24-72-h experiments with 3T3-L1 cells. The DLW increased cell viability at 48 h and inhibited adipogenesis in 3T3-L1 cells by reducing intracellular triglyceride levels and glucose uptake. In addition, mRNA and protein expression levels of adipogenesis-related genes were lowered by DLW, suggesting antiobesity effects in mouse 3T3-L1 cells. Because few studies have demonstrated cholesterol-lowering effects of D. morbiferus, we investigated the activities of adipogenic transcriptional factors following treatments of 3T3-L1 cells with D. morbiferus and observed increased CEBPα, CEBPß, PPARγ, and SREBP1 activities in the cells, indicating that DLW extracts inhibit adipogenesis.

Extracts of Porphyra tenera (Nori Seaweed) Activate the Immune Response in Mouse RAW264.7 Macrophages via NF-κB Signaling.

Porphyra tenera, also known as nori, is a red algal species of seaweed. It is cultivated in Asia for culinary purposes. We report that P. tenera extract (PTE) enhances the immune response in mouse macrophages. We found that P. tenera extract regulates the NF-κB IκB kinase (IKK) signaling pathway, and we assessed the expression and translocation of p65, a subunit of NF-κB, in RAW264.7 mouse macrophage cells after treatment with PTE. We also investigated the effects of 10% ethanol PTE (PTE10) in RAW264.7 cells. The production of IL-10, IL-6, TNF-α, and IFN-γ was induced by PTE treatment of the macrophages, and PTE also enhanced p-IκB and p-AKT. PTE10 showed no cytotoxicity at 10-20 µg/mL in RAW264.7 cells. PTE10, in fact, increased cell viability at 24 h, stimulated macrophage cells, and induced the phosphorylation of Akt. Akt stimulates IKK activity through the phosphorylation of IKKα and enhances immune activity through the activation of NF-κB. In this study, NF-κB activation was induced by increasing p-NF-κB and p-IKK. A subunit of NF-κB, p65, was located in the nucleus and increased the expression of various cytokines. PTE thus enhanced the immune response through IκB-α immunostimulation signaling in RAW264.7 cells. PTE10 has potential therefore for development of future treatments requiring immune system stimulation.

Anti-Adipogenic Effects of Ethanol Extracts Prepared from Selected Medicinal Herbs in 3T3-L1 Cells.

Obesity is a major risk factor for various metabolic diseases such as cardiovascular disease, hypertension, and type 2 diabetes mellitus. In this study, we prepared ethanol extracts from Agastache rugosa (ARE), Chrysanthemum zawadskii (CZE), Mentha arvensis (MAE), Perilla frutescens (PFE), Leonurus sibiricus (LSE), Gardenia jasminoides (GJE), and Lycopus coreanus (LCE). The anti-oxidant and anti-adipogenic effects were evaluated. The IC50 values for ascorbic acid and LCE against 2,2-diphenyl-1-picrylhydrazyl radicals were 246.2 µg/mL and 166.2 µg/mL, respectively, followed by ARE (186.6 µg/mL), CZE (198.6 µg/mL), MAE (337.1 µg/mL), PFE (415.3 µg/mL), LSE (548.2 µg/mL), and GJE (626.3 µg/mL). In non-toxic concentration ranges, CZE had a strong inhibitory effect against 3T3-L1 adipogenes (84.5%) than those of the other extracts. Furthermore, the anti-adipogenic effect of CZE is largely limited in the early stage of adipogenesis, and we revealed that the inhibitory role of CZE in adipogenesis is required for the activation of Wnt signaling. Our results provide scientific evidence that the anti-adipogenic effect of CZE can be applied as an ingredient for the development of functional foods and nutri-cosmetics for obesity prevention.

Anti-oxidant and anti-adipogenic effects of acorn (Quercus acutissima CARR.) shell extracts via regulation of wnt signaling in 3T3-L1 cells.

Acorn (Quercus acutissima CARR.) is a nut from the Fagaceae family that has been used in traditional medicine for many years. However, shells from acorns are regarded as a by-product and are mostly discarded. Anti-adipogenic activities of acorn shells were investigated using 3T3-L1 cells and methanol shell extracts (AE-M). AE-M demonstrated Cu2+-chelation activities and anti-oxidant activities via reduction of oxidative stress levels induced using AAPH. Six days after adipocyte differentiation, 50 and 100 µg/mL AE-M completely suppressed 3T3-L1 adipogenesis and the anti-adipogenic effect was stronger than for the positive control 50 µM quercetin. Treatment with AE-M in 3T3-L1 cells reduced mRNA expression levels of adipogenic genes. AE-M-inhibition was found in pre-adipogenic, early, and intermediate stages of adipogenesis in 3T3-L1 cells. The Wnt/ß-catenin signaling pathway is required for AE-M-inhibition of 3T3-L1 adipogenesis.

Anti-aging Potential of Extracts Prepared from Fruits and Medicinal Herbs Cultivated in the Gyeongnam Area of Korea.

Many recent studies have focused on maintaining a healthy life by preventing and/or postponing the aging process. Numerous studies have reported that continuous exposure to reactive oxygen species can stimulate skin aging and that excessive accumulation of fat can cause an impaired skin barrier and tissue structure alterations. Thus, the maintenance of antioxidant homeostasis and the suppression of adipose accumulation are important strategies for skin anti-aging. Here, we prepared three types of extracts [whole juice, acetone-perchloric acid (PCA), and ethanol] from 20 fruits and medicinal herbs native to the Gyeongnam area of Korea. The total phenolic content of each extract was analyzed, and we observed higher total phenolic contents in the medicinal herbs. Consistent with this, the results of the oxygen radical absorbance activity capacity assay indicated that the in vitro antioxidant activities of the medicinal herb extracts were stronger than those of the fruit extracts. The fruits and medicinal herbs had strong effects on cell-based systems, including H2O2-induced oxidative stress in human keratinocytes and 3T3-L1 lipid accumulation. Nishimura Wase persimmon, Taishu persimmon, wrinkled giant hyssop, sweet wormwood, Chinese cedar, red perilla, tan shen, hiyodori-jogo, and cramp bark may be natural anti-aging materials with effective antioxidant and anti-adipogenic activities. Taken together, our findings may provide scientific evidence supporting the development of functional foods and nutraceuticals from fruits and medicinal herbs.

A phenolic acid phenethyl urea derivative protects against irradiation-induced osteoblast damage by modulating intracellular redox state.

Because irradiation may cause osteoradionecrosis, antioxidant supplementation is often used to suppress irradiation-mediated injury. This study examined whether a synthetic phenethyl urea compound, (E)-1-(3,4-dihydroxyphenethyl)-3-(3,4-dihydroxystyryl)urea (DPDS-U), prevents irradiation-mediated cellular damage in MC3T3-E1 osteoblastic cells. A relatively high dose of irradiation (>4 Gy) decreased cell viability and proliferation and induced DNA damage and cell cycle arrest at the G(2)/M phase with the attendant increase of cyclin B1. Irradiation with 8 Gy induced intracellular reactive oxygen species (ROS) production and lipid peroxidation, and reduced glutathione content and superoxide dismutase activity in the cells. These events were significantly suppressed by treatment with 200 µM DPDS-U or 5 mM N-acetyl cysteine (NAC). DPDS-U or irradiation alone significantly increased heme oxygenase-1 (HO-1) expression and nuclear factor E2 p45-related factor-2 (Nrf2) nuclear translocation. Interestingly, pretreatment with DPDS-U facilitated irradiation-induced activation of the Nrf2/HO-1 pathway. The potential of DPDS-U to mediate HO-1 induction and protect against irradiation-mediated cellular damage was almost completely attenuated by transient transfection with Nrf2-specific siRNA or treatment with a pharmacological HO-1 inhibitor, zinc protoporphyrin IX. Additional experiments revealed that DPDS-U induced a radioprotective mechanism that differs from that induced by NAC through activation of Nrf2/HO-1 signaling. Collectively, our data suggest that DPDS-U-induced radioprotection is due to its dual function as an antioxidant to remove directly excessive intracellular ROS and as a prooxidant to stimulate intracellular redox-sensitive survival signal.

Polyphenon-60 displays a therapeutic effect on acne by suppression of TLR2 and IL-8 expression via down-regulating the ERK1/2 pathway.

Propionibacterium acnes (P. acnes) is a well-known acne-inducing factor which causes inflammatory skin lesions by enhancing cytokine production through toll-like receptor 2 (TLR2). Green tea extract catechin has been documented to possess anti-inflammatory effects. However, little is known about the mechanisms involved or any direct effect of green tea catechin on acne. The present study investigated the therapeutic effects and mechanism of polyphenon-60, also known as green tea catechin compound, on acne in vitro and in vivo. In a clinical study using topical polyphenon-60 treatment, acne patients showed symptomatic improvement with decrease in the number of comedos and pustules. To investigate the mechanism underlying the activity of polyphenon-60 in acne therapy, an in vitro study was performed. We found that polyphenon-60 reduced the levels of P. acnes-enhanced TLR2 and interleukin-8 (IL-8) in THP-1 cells, human monocyte cell line and human primary monocytes. Taken together, these data demonstrate that polyphenon-60 has a therapeutic effect on acne by suppressing inflammation, specifically by inhibiting TLR2 expression and IL-8 secretion via down-regulation of extracellular signal-regulated kinases 1/2 (ERK1/2) pathway and activator protein-1 (AP-1) pathway.

Heat processing decreases Amadori products and increases total phenolic content and antioxidant activity of Korean red ginseng.

The functional properties of Korean red ginseng (KRG) are known to be dependent upon the extent of heat processing. We demonstrated that repeated heat processing in the preparation of KRG decreased its arginyl-fructosyl-glucose (AFG) content and metal chelating capacity. On the other hand, the total phenolic compound content, in vitro peroxyl radical scavenging ability, and cellular peroxyl and hydroxyl radical scavenging ability increased with repeated heat processing. The peroxyl radical scavenging ability of KRG may be due to the total phenolic compound content. The hydroxyl radical scavenging ability of KRG seems to result mainly from the chelating ability of Amadori compounds such as arginyl-fructose and AFG. The protective ability of KRG against Cu²(+)-induced oxidative stress in hepatoma HepG2 cells may be due to permeability into the cell membrane rather than antioxidant activity. These results can be used to predict the physiological functions of KRG in in vivo models.

Antimicrobial activities of 1,4-benzoquinones and wheat germ extract.

We evaluated the antibacterial activities of selected edible Korean plant seeds against the food-borne pathogens Staphylococcus aureus KCTC1927, Escherichia coli KCTC2593, Salmonella typhimurium KCTC2054, and Bacillus cereus KCTC1014. While screening for antibacterial agents, we discovered that wheat germ extract contains 2,6-dimethoxy-1,4-benzoquinone (DMBQ) and is highly inhibitory to S. aureus and B. cereus. This is the first report of the antibacterial activity of wheat germ extract. We also investigated the antibacterial activities of the 1,4- benzoquinone standards 1,4-benzoquinone (BQ), hydroquinone (HQ), methoxybenzoquinone (MBQ), and 2,6-dimethoxy- 1,4-benzoquinone (DMBQ). DMBQ and BQ were the most highly inhibitory to S. aureus and S. typhimurium, followed by MBQ and HQ. MICs for DMBQ and BQ ranged between 8 and 64 microgram/ml against the four foodborne pathogens tested. DMBQ and BQ showed significant antibacterial activity; the most sensitive organism was S. aureus with an MIC of 8 microgram/ml. BQ exhibited good activity against S. typhimurium (32 microgram/ml) and B. cereus (32 microgram/ml). The results suggest that wheat germ extract has potential for the development of natural antimicrobials and food preservatives for controlling foodborne pathogens.

Feasibility of neuroendoscopic biopsy of pediatric brain tumors.

PURPOSE: The purpose of this study was to investigate the potential value of neuroendoscopic biopsies in pediatric patients with peri- or intraventricular tumors. METHODS: From 2001 to 2008, 49 pediatric patients (mean age, 12.16 years) with tumors located in the intraventricular or paraventricular areas underwent neuroendoscopic biopsy, with or without simultaneous endoscopic third ventriculostomy. Neuroendoscopic biopsies were performed to verify the histological diagnosis of neoplasms and to establish pathological diagnoses necessary for planning appropriate treatment strategies. RESULTS: In 45 of 49 patients (91.8%) neuroendoscopic biopsy specimens were appropriate for diagnosis and revealed 27 germinomas, 11 astrocytomas, and one ependymoma, etc. The tumor location included the pineal gland (n = 28), thalamus (n = 7), intraventricle (n = 3), hypothalamus (n = 3), suprasellar area (n = 2), and diffuse multifocal area (n = 3). In two patients (4.1%) biopsy specimens were informative but not diagnostic. Tumor tissue specimens were undiagnostic in two patients (4.1%). There were eight transient morbidities, including four EOM limitations, two central DI, one EVD infection, and one CSF leakage. One patient experienced postoperative tumor bleeding requiring emergent operation. There was no case of operative mortality. CONCLUSION: Neuroendoscopic biopsy can be considered as the first choice for tissue sampling of periventricular and intraventricular tumors with acceptable risks.