Leaves and pseudostems extract of Curcuma longa attenuates immunoglobulin E/bovine serum albumin-stimulated bone marrow-derived cultured mast cell activation and passive cutaneous anaphylaxis in BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma longa, known as turmeric, is an herbaceous perennial plant belonging to the genus Curcuma. It is dispersed throughout tropical and subtropical regions worldwide. Since ancient times, turmeric has been used as an ethnomedicinal plant in the Ayurvedic system, particularly in Asian countries. Rhizomes of turmeric possess several pharmacological properties that give high value as a medicinal remedy for treating a range of conditions, including inflammation, pain, allergies, and digestive issues. Moreover, turmeric leaves and pseudostems also contain a variety of health-enhancing secondary metabolites, such as curcumin, flavonoids, and other phenolic compounds, which exhibit anti-inflammatory, antitumor, antibacterial, and antioxidant properties. AIM OF THE STUDY: Allergic diseases are a group of immune-mediated disorders mainly caused by an immunoglobulin E (IgE)-dependent immunological response to an innocuous allergen. Therefore, this study aimed to investigate the effect of leaves and pseudostems extract of turmeric (TLSWE-8510) on IgE/bovine serum albumin (BSA)-stimulated allergic responses in mouse bone marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in BALB/c mice. MATERIALS AND METHODS: The effect of TLSWE-8510 on mast cell degranulation has been evaluated by investigating the release of ß-hexosaminidase and histamine in IgE/BSA-stimulated BMCMCs. Additionally, anti-allergic properties of TLSWE-8510 on IgE/BSA-stimulated BMCMCs were investigated using suppression of nuclear factor-kappa B (NF-κB), and spleen tyrosine kinase (Syk)-linker for T-cell activation (LAT)-extracellular-signal-regulated kinase (ERK)-GRB2 associated binding protein 2 (Gab2) signaling pathway and downregulation of allergy-related cytokines and chemokines expression. Furthermore, in vivo, studies were conducted using IgE-mediated PCA in BALB/c mice. RESULTS: TLSWE-8510 treatment significantly inhibited the degranulation of IgE/BSA-stimulated BMCMCs by inhibiting the release of ß-hexosaminidase and histamine dose-dependently. Additionally, TLSWE-8510 reduced the expression of high-affinity IgE receptors (Fc epsilon receptor I-FcεRI) on the surface of BMCMCs and the binding of IgE to FcεRI. Besides, the expression of cytokines and chemokines is triggered by IgE/BSA stimulation via activating the allergy-related signaling pathways. TLSWE-8510 dose-dependently downregulated the mRNA expression and the production of allergy-related cytokines (interleukin (IL)-1ß, IL-3, IL-4, IL-5, IL-6, IL-13, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ), and chemokines (thymus and activation-regulated chemokine (TARC), and regulated upon activation, normal T cell expressed and secreted (RANTES)) by regulating the phosphorylation of downstream signaling molecules, NF-κB, and Syk, LAT, ERK and Gab2 in IgE/BSA-stimulated BMCMCs. Moreover, PCA reaction in IgE/BSA-stimulated BALB/c mice ears was effectively decreased by TLSWE-8510 treatment in a dose-dependent manner. CONCLUSIONS: These results collectively demonstrated that TLSWE-8510 suppressed mast cell degranulation by inhibiting the release of chemical mediators related to allergies. TLSWE-8510 downregulated the allergy-related cytokines and chemokines expression and phosphorylation of downstream signaling molecules in IgE/BSA-stimulated BMCMCs. Furthermore, in vivo studies with IgE-mediated PCA reaction in the BALB/c mice ears were attenuated by TLSWE-8510 treatment. These findings revealed that TLSWE-8510 has the potential as a therapeutic agent for the treatment of allergic diseases.

Sleep Onset Problems and Subcortical Development in Infants Later Diagnosed With Autism Spectrum Disorder.

OBJECTIVE: Sleep patterns in children with autism spectrum disorder (ASD) appear to diverge from typical development in the second or third year of life. Little is known, however, about the occurrence of sleep problems in infants who later develop ASD and possible effects on early brain development. In a longitudinal neuroimaging study of infants at familial high or low risk for ASD, parent-reported sleep onset problems were examined in relation to subcortical brain volumes in the first 2 years of life. METHODS: A total of 432 infants were included across three study groups: infants at high risk who developed ASD (N=71), infants at high risk who did not develop ASD (N=234), and infants at low risk (N=127). Sleep onset problem scores (derived from an infant temperament measure) were evaluated in relation to longitudinal high-resolution T1 and T2 structural imaging data acquired at 6, 12, and 24 months of age. RESULTS: Sleep onset problems were more common at 6-12 months among infants who later developed ASD. Infant sleep onset problems were related to hippocampal volume trajectories from 6 to 24 months only for infants at high risk who developed ASD. Brain-sleep relationships were specific to the hippocampus; no significant relationships were found with volume trajectories of other subcortical structures examined (the amygdala, caudate, globus pallidus, putamen, and thalamus). CONCLUSIONS: These findings provide initial evidence that sleep onset problems in the first year of life precede ASD diagnosis and are associated with altered neurodevelopmental trajectories in infants at high familial risk who go on to develop ASD. If replicated, these findings could provide new insights into a potential role of sleep difficulties in the development of ASD.

Abundant storage protein depletion from tuber proteins using ethanol precipitation method: Suitability to proteomics study.

High-abundance proteins (HAPs) hamper in-depth proteome study necessitating development of a HAPs depletion method. Here, we report a novel ethanol precipitation method (EPM) for HAPs depletion from total tuber proteins. Ethanol showed a dose-dependent effect on depletion of sporamin from sweet potato and patatin from potato tubers, respectively. The 50% ethanol was an optimal concentration. 2DE analysis of EPM-prepared sweet potato proteins also revealed enrichment of storage proteins (SPs) in ethanol supernatant (ES) resulting in detection of new low-abundance proteins in ethanol pellet (EP), compared to total fraction. The ES fraction showed even higher trypsin inhibitor activity than total proteins, further showing the efficacy of EPM in enrichment of sporamin in ES fraction. Application of this method was demonstrated for comparative proteomics of two sweet potato cultivars (Hwang-geum and Ho-bac) and purification of SP (sporamin) in its native form, as examples. Comparative proteomics identified many cultivar specific protein spots and selected spots were confidently assigned for their protein identity using MALDI-TOF-TOF analysis. Overall, the EPM is simple, reproducible, and economical for depletion of SPs and is suitable for downstream proteomics study. This study opens a door for its potential application to other tuber crops or fruits rich in carbohydrates.

The effect of meditation on brain structure: cortical thickness mapping and diffusion tensor imaging.

A convergent line of neuroscientific evidence suggests that meditation alters the functional and structural plasticity of distributed neural processes underlying attention and emotion. The purpose of this study was to examine the brain structural differences between a well-matched sample of long-term meditators and controls. We employed whole-brain cortical thickness analysis based on magnetic resonance imaging, and diffusion tensor imaging to quantify white matter integrity in the brains of 46 experienced meditators compared with 46 matched meditation-naïve volunteers. Meditators, compared with controls, showed significantly greater cortical thickness in the anterior regions of the brain, located in frontal and temporal areas, including the medial prefrontal cortex, superior frontal cortex, temporal pole and the middle and interior temporal cortices. Significantly thinner cortical thickness was found in the posterior regions of the brain, located in the parietal and occipital areas, including the postcentral cortex, inferior parietal cortex, middle occipital cortex and posterior cingulate cortex. Moreover, in the region adjacent to the medial prefrontal cortex, both higher fractional anisotropy values and greater cortical thickness were observed. Our findings suggest that long-term meditators have structural differences in both gray and white matter.

Herbal cocktail ka-mi-kae-kyuk-tang stimulates mouse bone marrow stem cell hematopoiesis and janus-activated kinase 2/signal transducer and activator of transcription 5 pathway.

Ka-mi-kae-kyuk-tang (KMKKT) is an Oriental herbal medicinal cocktail. Our collaborative team has shown that it has potent anti-angiogenic, anti-cancer and anti-metastatic activities in vivo without observable side effects. We have documented evidence for KMKKT to alleviate drug-induced hematotoxicity in vivo. In the present study, we investigated the mechanistic and signaling events through which KMKKT enhances hematopoiesis, using hematopoietic stem cells (HSCs) isolated from the bone marrow of 8-12 week-old C57BL/6 mice. Our results show that KMKKT significantly increased the expression of the hematopoietic cytokines interleukin (IL)-3, stem cell factor (SCF), granulocyte-macrophage-colony stimulating factor (GM-CSF), thrombopoietin (TPO) and erythropoietin (EPO) at the level of mRNA and secretion in HSCs. KMKKT also increased the expression of c-Kit, a cytokine receptor expressed in HSCs. In addition, KMKKT enhanced phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5), and increased the binding activity of STAT5 to gamma interferon activated sites (GAS) that mediate JAK2 downstream signaling. Furthermore, we found that KMKKT significantly enhanced the growth rate of colony-forming unit granulocyte erythrocyte monocyte macrophages (CFU-GEMM) and burst forming unit erythroid (BFU-E) of mouse HSCs (mHSCs) stimulated by IL-3/EPO. Overall, our results demonstrated that KMKKT alleviated drug-induced side effects through enhanced hematopoiesis, at least in part through cytokine-mediated JAK2/STAT5 signaling.

JAK2/STAT5 signaling pathway mediates Bojungbangdocktang enhanced hematopoiesis.

Bojungbangdocktang (BJBDT) is a medicinal herbal cocktail that has been used for cancer prevention and treatment in traditional Korean medicine. In the current study, BJBDT was demonstrated to regulate hematopoiesis. BJBDT significantly increased the expression of hematopoietic cytokines interleukin (IL)-3, stem cell factor (SCF), granulocyte-macrophage-colony stimulating factor (GM-CSF), thrombopoietin (TPO) and erythropoietin (EPO) at the level of mRNA and secretion in hematopoietic stem cells (HSCs). Additionally, BJBDT enhanced the phosphorylation of Janus activated kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) and STAT binding to gamma interferon activated sites (GAS) in HSCs. Furthermore, BJBDT significantly enhanced the growth rate of granulocyte erythrocyte monocyte macrophage colony-forming units (CFU-GEMM) and erythroid burst forming units (BFU-E) in vitro. Moreover, BJBDT increased the level of EPO at mRNA in kidney and plasma, and the numbers of erythroid-specific antigen Ter-119(+) erythroid cells in mice with aplastic anemia induced by 20% benzene. Consistently, histochemical staining revealed BJBDT increased the bone marrow and stromal cells as well as decreased macrophages and adipocytes in bone marrow tissues of mice with aplastic anemia. Taken together, the results suggest that BJBDT can enhance hematopoiesis via hematopoietic cytokine-mediated JAK2/STAT5 pathway as a potent hematopoietic candidate. Copyright © 2010 John Wiley & Sons, Ltd.

1,2,3,4,6-Penta-O-galloly-beta-D-glucose suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1α and signaling in LNCaP prostate cancer cells.

Hypoxia is the hallmark of solid tumors and contributes to tumor angiogenesis mainly through activation of the transcription factor hypoxia-inducible factor-1 (HIF-1). In addition to upregulating vascular endothelial growth factor (VEGF) in angiogenesis, HIF-1 plays critical roles in the metabolism, proliferation, metastasis, and differentiation of cancer cells. We and others have previously shown that 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) from Oriental herbal medicine possesses anti-angiogenic, anti-tumorigenic, and anti-diabetic activities. In the present study, we report that PGG inhibits hypoxia-induced protein accumulation, transcriptional activation, and mRNA expression of HIF-1α in LNCaP prostate cancer cells. PGG reduced cellular and secreted VEGF levels as well as mRNA expression in LNCaP cells. PGG suppressed capillary tube formation in human umbilical vein endothelial cells (HUVECs) maintained in conditioned medium of hypoxia-induced LNCaP cells, indicating that PGG has anti-angiogenic activity under hypoxic condition. Furthermore, PGG reduced expression of phosphoinositide 3-kinase (PI3K) as well as phosphorylation of AKT and mammalian target of rapamycin (mTOR), but not extracellular signal-regulated kinase (ERK) in LNCaP cells under hypoxic condition. Consistently, LY294002, a specific PI3K inhibitor, enhanced the inactivation of HIF-1α and AKT by PGG in LNCaP cells. Taken together, our results demonstrate that PGG inhibits hypoxia-mediated accumulation of HIF-1α as well as its downstream signaling to VEGF and PI3K/AKT/mTOR pathway in LNCaP prostate cancer cells.

Traditional medicine Taeeumjowitangkagambang exerts antiobesity and hypolipidemic effects via antioxidant enzyme enhancement.

Taeeumjowitangkagambang (ETJKB) is a traditional Korean medicine that has been clinically used for obesity with little mechanistic understanding. The present study investigated antiobesity and hypolipidemic effects of ETJKB in high fat diet fed rats as well as a 3T3-L1 pre-adipocyte differentiation model. ETJKB significantly inhibited the lipidogenesis in 3T3-L1 adipocytes in a concentration-dependent manner as well as reduced the cellular adipokine leptin level. Daily oral gavage of ETJKB to rats fed a high fat diet significantly attenuated body weight gain and abdominal and epididymal fat weights. ETJKB treatment also reduced the levels of total cholesterol, low density lipoprotein (LDL) and triglyceride as well as increased high density lipoprotein (HDL) in serum compared with the untreated control. Similarly, the ETJKB treatment decreased the levels of total lipid, triglyceride and cholesterol in liver tissue in high fat diet fed rats. Interestingly, ETJKB significantly increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase in liver tissue, while decreasing the hydroxyl radical, thiobarbituric acid reactive substances (TBARS), carbonyl concentration. An improvement of antioxidant enzymes was associated with improved body weight control and healthier lipid profiles and therefore may play an important role in the antiobesity and hypolipidemic effects of ETJKB.

Ethanol extract of Ocimum sanctum exerts anti-metastatic activity through inactivation of matrix metalloproteinase-9 and enhancement of anti-oxidant enzymes.

Ocimum sanctum has been known to possess various beneficial properties including anti-oxidative, anti-inflammatory and anti-cancer activities. In the present study, we investigated that ethanol extracts of O. sanctum (EEOS) had anti-metastatic activity through activation of anti-oxidative enzymes. EEOS exerted cytotoxicity against Lewis lung carcinoma (LLC) cells. Also, EEOS significantly inhibited cell adhesion and invasion as well as activities of matrix metalloproteinase-9 (MMP-9), but not MMP-2, indicating the important role of MMP-9 in anti-metastatic regulation of EEOS. In addition, EEOS significantly reduced the tumor nodule formation and lung weight in LLC-injected mice. Inhibitory effect of EEOS on metastasis was further confirmed by using hematoxylin and eosin (H&E) staining. Notably, we also found that EEOS enhanced activities of anti-oxidative enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in a concentration-dependent manner. Taken together, our findings support that EEOS can be a potent anti-metastatic candidate through inactivation of MMP-9 and enhancement of anti-oxidant enzymes.

Substance P and beta-endorphin mediate electro-acupuncture induced analgesia in mouse cancer pain model.

BACKGROUND: Opioid analgesics are generally used to combat the pain associated with cancerous conditions. These agents not only inhibit respiratory function and cause constipation, but also induce other significant side effects such as addiction and tolerance, all of which further contribute to a reduced quality of life for cancer patients. Thus, in the present study, the effects of electro-acupuncture treatment (EA) on mechanical allodynia were examined in a cancer pain mouse model. METHODS: In order to produce a neuropathic cancer pain model, S-180 sarcoma cells were inoculated around the sciatic nerve of left legs of Balb/c mice. Magnetic Resonance Imaging (MRI) scanning confirmed the mass of S-180 cancer cells embedded around the sciatic nerve. Mechanical allodynia was most consistently induced in the mouse sarcoma cell line S-180 (2 x 10(6)sarcoma cells)-treated group compared to all the other groups studied. EA stimulation (2 Hz) was administered daily to ST36 (Zusanli) of S-180 bearing mice for 30 min for 9 days after S-180 inoculation. RESULTS: EA treatment significantly prolonged paw withdrawal latency from 5 days after inoculation. It also shortened the cumulative lifting duration from 7 days after inoculation, compared to the tumor control. Also, the overexpression of pain peptide substance P in the dorsal horn of the spinal cord was significantly decreased in the EA-treated group compared to the tumor control on Day 9 post inoculation. Furthermore, EA treatment effectively increased the concentration of beta-endorphin in blood and brain samples of the mice to a greater extent than that of the tumor control as well as the normal group. The concentration of beta-endorphin for EA treatment group increased by 51.457% in the blood and 12.6% in the brain respectively, compared to the tumor control group. CONCLUSION: The findings of this study suggest that a S-180 cancer pain model is useful as a consistent and short time animal model. It also indicated that EA treatment could be used as an alternative therapeutic method for cancer pain due to a consequent decrease in substance P and increase in beta-endorphin levels.

[King Jung-jo's medical philosophy].

King Jungjo who introduced the advent of cultural renaissance of Chosun Dynasty as little been known about his work in medicine. With a wide knowledge in medicine, he was the only one among the kings who wrote a book on medicine, called "SueMinMyoJeon". In this paper, his perspective on medicine will be looked into based on "The Annals of the Chosun Dynasty", "Seungjeongwon Ilgi", "Hong Je jun Se", "KukGoBoGam", "Ildkrok", "JeJungShinPyun", "SueMinMyoJeon" etc. King Jungo valued empiricism in the field of medicine. He deepened understandings in medicine while taking care of King Youngjo, the late king. And it led him to author "SueMinMyoJeon" himself, and further ordered the publications of "JeJungShinPyun" "MaGuaHeoiTong". These two books were conducted to include empirical cases of folklore remedy. King Jungjo's medical philosophy can be epitomized in filial piety and realization of people-serving politics, which are the essentials of Confucianism. His filial piety towards the late king, Youngjo and his mother is shown in his devotion when taking care of them. Especially the way he examined the differentiation of diseases and corresponding treatments is well described in "The Annals of the Chosun Dynasty". "JeJungShinPyun" was also published and it came handy for folk villagers in times of medical needs. Later this book influenced "BangYakHaepPyun" by Hwang Do Yeon. King Jungjo emphasized pragmatism in spreading medical knowledges, thus removing the theoretical contents that are related to Taoism, especially the ones on alchemy from "DongEuiBoGam", when publishing "SueMinMyoJeon". Even the excerpts from "SoMun" were taken out, if not practical. King Jungjo, however, discussed the importance of healthy regimen and mentioned himself practicing it from the book "IlDeukLok", which seems to be the only book that derailed from the pragmatistic track. King Jungjo put emphasis on consistency between diagnosis and treatment. In diagnosing, Meridian pulse was taken important as a means of finding the origin of disease, while deploring how doctors then neglected to study.

Thalamus surface shape deformity in obsessive-compulsive disorder and schizophrenia.

The authors performed a three-dimensional shape deformation analysis to clarify the various patterns of specific thalamic nuclei abnormality using three age-matched and sex-matched groups of 22 patients with obsessive-compulsive disorder (OCD), 22 patients with schizophrenia and 22 control participants. Compared with the healthy volunteers, the anterior, lateral outward surface deformities of the thalamus were significant in OCD patients, whereas the posterior, medial outward deformities of the thalamus were prominent in schizophrenia patients. In terms of thalamic asymmetry, both OCD and schizophrenia patients exhibited the loss of a leftward pattern of asymmetry on the posterior, medial surface of the thalamus. Different patterns of shape abnormality of specific thalamic nuclei may be related to the different phenomenology of OCD and schizophrenia.

Enhanced tolerance of transgenic potato plants overexpressing nucleoside diphosphate kinase 2 against multiple environmental stresses.

In plants, nucleoside diphosphate kinase 2 (NDPK2) is known to regulate the expression of antioxidant genes. In this study, we developed transgenic potato plants (Solanum tuberosum L. cv. Atlantic) expressing Arabidopsis NDPK2 (AtNDPK2) gene in cytosols under the control of an oxidative stress-inducible SWPA2 promoter (referred to as SN plants) or enhanced CaMV 35S promoter (EN plants) and evaluated their tolerance to various environmental stress, including methyl viologen (MV)-mediated oxidative stress, high temperature, and salt stress. When 250 muM MV was sprayed to whole plants, plants expressing NDPK2 showed significantly an enhanced tolerance compared to non-transgenic (NT) plants. SN plants and EN plants showed 51% and 32% less visible damage than NT plants, respectively. Transcript level of AtNDPK2 gene and NDPK2 activity in SN plants following MV treatment well reflected the plant phenotype. Ascorbate peroxidase (APX) activity was also increased in MV-treated SN plants. In addition, SN plants showed enhanced tolerance to high temperature at 42 degrees C. The photosynthetic activity of SN plants after treatment of high temperature was decreased by about 10% compared to the plants grown at 25 degrees C, whereas that of NT plants declined by 30%. When treated with 80 mM NaCl onto the plantlets, both SN plants and EN plants also showed a significant reduced damage in root growth. These results indicate that overexpression of NDPK2 under the stress-inducible SWPA2 promoter might efficiently regulate the oxidative stress derived from various environmental stresses.

Enhanced tolerance of transgenic potato plants expressing both superoxide dismutase and ascorbate peroxidase in chloroplasts against oxidative stress and high temperature.

Oxidative stress is a major damaging factor for plants exposed to environmental stresses. In order to develop transgenic potato plants with enhanced tolerance to environmental stress, the genes of both Cu/Zn superoxide dismutase and ascorbate peroxidase were expressed in chloroplasts under the control of an oxidative stress-inducible SWPA2 promoter (referred to as SSA plants). SSA plants showed enhanced tolerance to 250 microM methyl viologen, and visible damage in SSA plants was one-fourth that of non-transgenic (NT) plants that were almost destroyed. In addition, when SSA plants were treated with a high temperature of 42 degrees C for 20 h, the photosynthetic activity of SSA plants decreased by only 6%, whereas that of NT plants decreased by 29%. These results suggest that the manipulation of the antioxidative mechanism of the chloroplasts may be applied in the development of industrial transgenic crop plants with increased tolerance to multiple environmental stresses.

Functional characterization of OsRacB GTPase--a potentially negative regulator of basal disease resistance in rice.

The rice genome contains at least seven expressed Rop small GTPase genes. Of these Rops, OsRac1 is the only characterized gene that has been implicated in disease resistance as a positive regulator. To our interest in finding a negative ROP regulator of disease resistance in rice, we applied a "phylogeny of function" approach to rice Rops, and identified OsRacB based on its close genetic orthologous relationship with the barley HvRacB gene, a known negative regulator of disease resistance. To determine the function of OsRacB, we isolated the OsRacB cDNA and conducted gene expression and transgenic studies. OsRacB, a single copy gene in the genome of rice, shared 98% identity with HvRacB at the amino acid level. Its mRNA was strongly expressed in leaf sheath (LS) and in panicles, but was very weakly expressed in young and mature leaves. The basal mRNA level of OsRacB in LS of two-week-old seedlings was strongly down-regulated upon wounding by cut and treatment with jasmonic acid. A dramatic down-regulation in the OsRacB transcripts was also found in plants inoculated with the blast pathogen, Magnaporthe grisea. Interestingly, transgenic rice plants over-expressing OsRacB showed increased symptom development in response to rice blast pathogens. Additionally, fluorescence microscopy of green fluorescent protein (GFP):OsRacB-transformed onion cells and Arabidopsis protoplasts revealed OsRacB association with plasma membrane (PM), suggesting that PM localization is required for proper function of OsRacB. Based on these results, we suggest that OsRacB functions as a potential regulator for a basal disease resistance pathway in rice.