Berberine binds RXRα to suppress ß-catenin signaling in colon cancer cells.

Berberine, an isoquinoline alkaloid, is a traditional oriental medicine used to treat diarrhea and gastroenteritis. Recently, we reported that it could inhibit the growth of intestinal polyp in animals and in patients with the familial adenomatous polyposis by downregulating ß-catenin signaling. However, the intracellular target mediating the effects of berberine remains elusive. Here, we provide evidence that berberine inhibits ß-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binding to and synergistically activating RXRα with 9-cis-retinoic acid (9-cis-RA), a natural ligand binding to the classical ligand-binding pocket of RXRα. Berberine binding promotes RXRα interaction with nuclear ß-catenin, leading to c-Cbl mediated degradation of ß-catenin, and consequently inhibits the proliferation of colon cancer cells. Furthermore, berberine suppresses the growth of human colon carcinoma xenograft in nude mice in an RXRα-dependent manner. Together, our study not only identifies RXRα as a direct protein target for berberine but also dissects their binding mode and validates that berberine indeed suppresses ß-catenin signaling and cell growth in colon cancer via binding RXRα, which provide new strategies for the design of new RXRα-based antitumor agents and drug combinations.

Can anisodamine be a potential substitute for high-dose atropine in cases of organophosphate poisoning?

A case of organophosphate (OP) poisoning was admitted to the emergency room. The patient accepted treatment with pralidoxime (PAM), atropine, and supporting therapy. It was observed that even after 22 h after treatment, 960 mg of atropine was not enough for the patient to be atropinized. However, a 160-mg follow-up treatment of anisodamine was quite enough for atropinization after 4 h. As a case report, more studies are required before any definite conclusion can be reached regarding the use of anisodamine as a potential substitute for high-dose atropine in cases of OP poisoning.

Infrared spectroscopy of goethite dehydroxylation: III. FT-IR microscopy of in situ study of the thermal transformation of goethite to hematite.

Fourier transform infrared microscopy has been used to investigate in situ dehydroxylation of goethite to form hematite. The characterisation was based on the behaviour of hydroxyl units, which were observed in the hydroxyl stretching and hydroxyl deformation and water bending regions, and the Fe-O vibrations of the newly formed hematite during the thermal dehydroxylation process. Two hydroxyl stretching modes (v1 and v2), and three bending (V(bending-1, 2, 3)) and two deformation (V(deformation-1, 2)) modes were observed for goethite. The characteristic vibration at 916 cm(-1) was observed together with the residuals of the v1 and v2 bands in hematite spectrum. The structural transformation between goethite and hematite through thermal dehydroxylation was interpreted in order to provide criteria that can be used for the characterisation of thermally activated bauxite and their conversion to activated alumina phases.

Far-infrared spectroscopy of alumina phases.

Far-infrared spectroscopy (FIR) has been used to distinguish alumina phases boehmite, diaspore, gibbsite and bayerite. The pellets of samples were prepared by mixing alumina phases with polyethylene at a ratio of 1:50, and the spectra were recorded between 50 and 400 cm(-1). The spectrum of boehmite resembles that of diaspore in the 300-400 cm(-1) region. Boehmite has two characteristic FIR bands at 366 and 323 cm(-1), while diaspore has five at 354, 331, 250, 199 and 158 cm(-1). The spectrum of gibbsite resembles that of bayerite in the 230-300 cm(-1) region. Gibbsite shows three characteristic FIR bands at 371, 279 and 246 cm(-1), whereas bayerite shows six at 383, 345, 326, 296, 252 and 62 cm(-1). The overlapping bands were resolved, and the spectra were manipulated appropriately using band analysis techniques. The FIR spectra are in harmony with the FT-Raman spectra. Far-infrared spectroscopy allows the study and differentiation of the stretching of AlO4 units to characterize these four alumina phases. Far-IR spectroscopy complements the mid-IR and near-IR for distinguishing alumina phases in bauxites.

Effects of AP-V and bicuculline on somatostatin-positive neurons in hypothalamus of rats subjected to acute hypobaric hypoxia.

AIM: To investigate the effects of 2-amino-5-phosphonovalerate-pharmacology (AP-V) and bicuculline on somatostatin (SST)-positive neurons in hypothalamus of rats subjected to acute hypobaric hypoxia. METHODS: SST-immunoreactivity (IR) and somatostatin mRNA (SS mRNA)-positive neurons were measured by immunohistochemistry and in situ hybridization methods. RESULTS: Compared with control rats, SST-IR and SS mRNA-positive neurons in hypothalamic periventricular nucleus (PeV), paraventricular nucleus (PVN), and arcuate nucleus (ARC) increased after acute hypobaric hypoxia for 6 h (P < 0.01), and these effects were markedly inhibited by AP-V (10 microg, icv), a highly selective N-methyl-D-aspartate (NMDA) receptor antagonist, whereas were strongly enhanced by bicuculline (1.5 mg/kg, ip), a gamma-aminobutyric acid (GABAA) receptor antagonist. CONCLUSION: SST possibly participates in acute hypoxic reaction in hypothalamus, furthermore, glutamate and GABA can affect somatostatin release and synthesis in hypothalamus through NMDA and GABAA receptors respectively.

[Ketamine and L-NAME inhibit NOS and somatostatin mRNA expression induced by altitude hypoxia in the rat hypothalamus].

Using altitude hypoxia model, in situ hybridization and NADPH-d histochemistry, we investigated the effects of ketamine and L-NAME (blocker of NOS) on NOS and somatostatin mRNA (SS mRNA) expression in the rat hypothalamus following acute altitude hypoxia. It was revealed that acute altitude hypoxia induced NOS and SS mRNA overexpression in the rat hypothalamus. When pretreated with NMDA receptor antagonist ketamine and L-NAME, NOS and SS mRNA expression were inhibited significantly. These results suggest that NMDA receptor activation participates in the expression of NOS and SS mRNA in the rat hypothalamus subjected to acute altitude hypoxia. Meanwhile, hypothalamic endogenous NO may mediate expression of SS mRNA.

Effects of corticotrophin on pain behavior and BDNF, CRF levels in frontal cortex of rats suffering from chronic pain.

AIM: To investigate the effects of corticotrophin (Cor) on corticotropin-releasing factor (CRF), brain-derived neurotrophic factor (BDNF), and its functional receptor trkB in the frontal cortex of complete Freud's adjuvant (CFA)-induced arthritic rats. METHODS: The chronic pain rat model was modified and pain behaviour scores were assessed. BDNF-immunoreactivity (IR), trkB-IR, and CRF mRNA-positive neurons were measured by immunohistochemistry and in situ hybridization methods. RESULTS: Compared with control rats, pain behavior scores, BDNF-IR, CRF mRNA-positive, trkB-IR, and BDNF/CRF mRNA double-labeling neurons in the contralateral frontal cortex of the arthritic rats increased significantly at 24 h after injection of CFA (P < 0.05), and these effects were decreased markedly by i.p. injection of Cor (P < 0.05). The decrease in pain behavior and BDNF-IR, CRF mRNA levels in frontal cortex of arthritic rats due to Cor were partly prevented by adrenalectomy (ADX). CONCLUSION: The increment in BDNF and CRF levels in the contralateral frontal cortex of arthritic rats may be inhibited by corticotrophin.

[Excitatory amino acid enhance prepro-somatostatin mRNA expression induced by altitude hypoxia in the rat hypothalamus].

AIM AND METHODS: Contents of glutamate (Glu), asparate (Asp) and expression of prepro-somatostatin mRNA (PPS-mRNA) in rat hypothalamus were measured by using imitated altitude hypoxia rat model, amino acid analyzer and in situ hybridization technique. RESULTS: After rats were subjected to altitude hypoxia, contents of Glu and Asp in hypothalamus and PPS-mRNA expression in periventricular nucleus (PeVN), paraventricular nucleus (PaVN) and arcuate nucleus (ArcN) were increased significantly. Ketamine, a NMDA receptor antagonist, could decrease the number of PPS-mRNA neurons in rat hypothalamus evoked by altitude hypoxia, but had no effect on Glu and Asp contents evoled by altitude hypoxia. CONCLUSION: It is suggested that somatostatin maybe paticipate in altitude hypoxia reaction, Glu can enhance PPS-mRNA expression through NMDA receptor.

[Studies on immunomodulatory function of polysaccharide of Fructus Ligustri Lucidi].

OBJECTIVE: To explore the immunomodulatory mechanism of Chinese medicine Fructus Ligustri Lucidi and to find its efficient material base. METHOD: The effects of FLLPS on the immunoactivity of mouse speen lymphocyte were studied in vitro or vivo by means of MTT. RESULT: FLLPS could obviously promote the speen lymphocyte proliferation in normal mice and mice with Yin-deficiency selected by injection with adrenocorticortropic hormone. CONCLUSION: FLLPS has an immunomodulatory function for both normal mice and mice with Yin-deficiency.

[Somatostatin and electroacupuncture inhibited c-fos expression in spinal cord of arthritic rats].

AIM: To observer the effect of intrathecal injection of somatostatin (Som) associated with electroacupuncture (EA) at "Jiaji" points on c-fos protein expression of spinal cord in pain rats. METHODS: Rats with adjuvant arthritis were used as pain model and the c-fos-like immunoreactivity (FLI) was detected by immunohistochemistry. RESULTS: The c-fos protein expression induced by arthritis were found in all of the I-X laminae of ipsilateral spinal cord of rats, and most of the labeled cells were located in the laminae I-II and V-VI. Som and EA suppressed the c-fos expression and the lessening of FLI cells in the spinal cord. CONCLUSION: Pathological pain following arthritis activated pain sensitive neurons (PSN) and evoked c-fos expression in spinal cord, Som and EA suppressed activities of these PSN, producing the effect of analgesia.

[Effect of 5-HT and somatostatin on SP and chronic pain initiated electrical activity of neurons in spinal dorsal horn].

The effects of SP on the electric activities of neurons of spinal dorsal horn and the influence of 5-HT, somatostatin (SOM) on the effects of SP were observed in anesthetized rats with multimicropipete and iontophoresis techniques. It was found that: (1) The microiontophoretically administrating of SP could increase spinal dorsal horn unit discharge. (2) The noxious electrical activity of neurons induced by formalin could be inhibited by microiontophoretically applied SP. (3) The microiontophoretically administrating of 5-HT and SOM could inhibit the SP and formalin evoked unit discharge of neurons in spinal dorsal horn. It was suggested that SP took a double-effect part in modulation of pain transmission and analgesia in spinal cord, 5-HT and SOM inhibited the effect of SP and participated in pain modulation of SP.

[Effect of morphine on pain threshold and C-fos expression induced by substance P].

Using pain measurement and immunohistochemistry, we have observed that the intrathecal injection (it) SP produced dose-related pain response. A larger dose of SP (5 micrograms, 10 micrograms) could reduce the pain threshold and evoke c-fos expression, but no obvious effect was produced by a smaller dose of SP (0.5 microgram, 1 microgram). Morphine (it) not only increased the pain threshold, but also inhibited pain response and c-fos expression of spinal cord induced by it SP, the effects could be reversed by naloxone.

[Effect of brain somatostatin on electroacupuncture analgesia of rat].

The purpose of this study was to verify the role of somatostatin (Som) of brain in analgesia of electroacupuncture (EA). Intracerebroventricular (icv) injection of Som caused a more marked elevation of pain threshold and of EA analgesic effect, but the activity of Ca(2+)-APTase in hippocampus was significantly decreased; The Som and GABA levels in hippocampus and brain stem were decreased by EA analgesia. The Som in hippocampus and brain stem were obviously depleted by icv injection of cycteamine, but without any change of pain threshold and analgesic effect of EA. These results indicated that the exogenous Som of brain potentiated the analgesic effect of EA, however, the decrease of endogenous of some brain regions took part in the process of EA analgesia.

[Interaction between r-aminobutyric acid content of the brain regions and cell immunity in the analgesic effect of adrenocorticotropic hormone in rats].

After intraperitoneal injection of ACTH, the content of GABA in hippocampus and the pain threshold were increased. This effect could be decreased by cyclosporin. ACTH decreased SI of MSBT and production of IL-II, and this suppression could be reversed by GABA synthesis inhibitor isoniazid, or GABA receptor blocker picrotoxin. These results suggest that: the analgesic effect of ACTH is related with the increase of GABA content in hippocampus, and cell immunity could be involved the regulation of GABA content in the brain regions. ACTH inhibited the effect of cell immunity, and this effect related to GABA content. Above effect is at least partly mediated by GABA synthesis and GABA receptor.

[Effect of intracerebral injection of substance P on serotonin contents of several brain regions and its relation with pain threshold, electroacupuncture analgesia in rats].

The purpose of this study is to observe the effect of intracerebroventricular (icv) and intra-PAG injection of substance P (SP) on serotonin (5-HT) contents of hypothalamus, hippocampus, striatum and its relation with the change of pain threshold, electroacupuncture (EA) analgesia. The results were as follows: (1) After icv injection of SP, the pain threshold and the 5-HT contents of hypothalamus, hippocampus were significantly increased. After depletion of the 5-HT contents in brain by pCPA, the inhibitor of 5-HT synthesis, the effect of SP on elevating pain threshold and the 5-HT contents of hypothalamus, hippocampus were markedly attenuated, bud did not prevent the analgesic effect of SP (2) The pain threshold and the 5-HT contents of hypothalamus, hippocampus were dose-dependently increased by intra-PAG injection of SP. (3) The intra-PAG injection of SP introduced simultaneously with high or low frequency EA did not affect the change of 5-HT contents of three brain regions, but caused a more marked elevation of pain threshold. These results suggest that the serotoninergic system may be activated by PAG for the mediation of SP induced analgesia. There is a synergic action of analgesia between the effects produced by intra-PAG injection of SP and those by high or low frequency EA.

[Effect of monoamine neurotransmitters, enkephalin and morphine on substance P contents of several brain regions and pain threshold in rats].

The present work was carried out to observe the effect of intra-cerebroventricular (icv) injection of monoamine neurotransmitters, enkephalin and morphine on immunoreactive substance P(Ir-SP) contents in hypothalamus, striatum, hippocampus and pain threshold. The results were as follows: (1) After icv or intra-DR (dorsal raphe nucleus) injection of 5-HTP, the content of Ir-SP in hypothalamus significantly decreased and pain threshold markedly increased; After depletion of the 5-HT content in brain by pCPA or destruction of DR, the contents of Ir-SP were remarkably elevated in three brain regions by the former and in hypothalamus, striatum by the later. (2) The Ir-SP levels in the three brain regions and the pain threshold were not affected by the icv injection of NE, however, icv injection of DA caused a increase of Ir-SP concentration in striatum which was reversed by the DA receptor antagonist haloperidol, but without any change of the pain threshold. 7th day after icv injection of 6-OHDA, the content of Ir-SP in striatum significantly reduced. (3) Icv injection of met-enkephalin (MEK) or morphine could increase the Ir-SP levels in hypothalamus, striatum and the pain threshold, and above-mentioned effect of morphine could be prevented by the opioid receptor antagonist naloxone. Icv injection of leu-enkephalin (LEK) had no effects both on Ir-SP contents in three brain regions and the pain threshold.

[Relationship between the content of central substance P and the analgesic effect of electroacupuncture in rats].

Substance P(SP) immunoreactivity in the rat brain and spinal cord were measured by radioimmunoassay and studied to correlate with the analgesic effect induced by electroacupuncture (EA). The results showed following: (1) There was a significant elevation in SP levels sn the hippocampus, hypothalamus and striatum after 30 min of EA. There was a markedly fall in the spinal cord. Statistical analysis revealed a positive correlation between the EA effect and the SP content in hypothalamus, striatum and statistical analysis revealed a correlation. In the spinal cord. (p less than 0.01), while the SP content in the hippocampus exhibited a similar degree of elevation in non responsive and good responsive animals to EA stimulation. (2) SP levels in the hippocampus, hypothalamus and striatum were increased by electroacupuncture stimulation (3v). The frequency of 1.5Hz was no obvious difference as compared with 100Hz in the effects on brain SP content. (3) SP content in the spinal cord decreased only using electroacupuncture stimulations of combination of higher intensity (3v) and higher frequency (100 Hz). (4) This effect could be blocked by the naloxone (i.p) and LSD (icv), but icv injection of Met-enkephalin antibodies had no affects on them.