[A biographical study of Bernard Rhodes S. J. (1646-1715), physician, surgeon and insignis pharmacopeus: deciphering medical itineraries in Qing China].

The itinerary of Bernard Rhodes S. J. (1646-1715), temporal coadjutor of the Society of Jesus and missionary in China, is of remarkable complexity. He was already a doctor before he was recruited by the Jesuit order and sent on various missions. During the nine years before his arrival in China, his route between Europe and Asia was largely determined by rivalries between European powers. When he eventually arrived in Beijing in 1699 and entered the service of the Kangxi Emperor, he became attached to the Imperial House, and this seems to have decisively determined the course of his itineraries in the Middle Kingdom henceforth. Following his movements in the capital and in the emperor's cortege during imperial tours gives us unique insights into the mobility of this Jesuit medical practitioner. In the service of the Manchu rule, he provided therapies-unknown to Chinese palace physicians and their medical traditions-to privileged patients belonging to the core imperial networks. In the medical pluralistic setting as it existed at the court and was instrumentalized by the Manchu ruler for ideological purposes, Rhodes was in competition not only with experts of the Imperial Academy of Medicine, but also with Mongolian doctor and Lama therapists. His career in the Qing empire illustrates that the presence in Beijing of doctors trained in Europe was not enough to ensure the transmission of the specific knowledge they held. Medical matters reveal to be an important case study in which Western language sources, combined with those in Chinese and especially in Manchu, provide us with a deeper understanding of courtly live and the function of medicine in consolidating Manchu rule during the Kangxi reign. Thus, the study of the biography of Rhodes, one of the marginal actors in the emperor's service, and the tracing of his itineraries is a complementary contribution to New Qing History, with its emphasis on exploring non-Chinese voices.

The role of heat shock proteins in oxidative stress damage induced by Se deficiency in chicken livers.

Selenium (Se) is an essential dietary trace element, which acts as an antioxidant. Heat shock proteins (HSPs) are a family of intracellular proteins whose synthesis is greatly increased upon exposure of cells to environmental stressors including oxidative metabolites, heavy metals, amino acid analogues and so on. However, little is known about the role of HSPs in oxidative stress damage induced by Se deficiency in the chicken liver. The aim of this study was to investigate the effects of Se deficiency on the expression levels of HSPs (Hsps27, 40, 60, 70, and 90) and oxidative indexes in the chicken liver. A total of 300 1-day-old sea blue white laying hens were divided into two groups (n = 150/group), and each of those groups was randomly divided into groups so that the trials were conducted in triplicate. The Se-deficient group (-Se) was fed a Se-deficient corn-soy basal diet (the Se content was 0.02 mg/kg); the Se-adequate group as control (+Se) was fed the same basal diet supplemented with Se at 0.2 mg/kg (sodium selenite). The liver tissue was collected and examined for pathological observations, oxidative indexes, mRNA and protein levels of HSPs genes at 15, 25, 35, 45, 55 and 65 days old. The histopathological analysis showed that liver tissues were injured seriously in the Se-deficient group. The oxidative indexes data showed that the malondialdehyde (MDA) level increased and the activity of L-glutathione (GSH) and glutathione peroxidase (GSH-Px) in the chicken liver decreased in Se-deficient group (p < 0.05). Additionally, the mRNA levels of HSPs (27, 40, 60, 70, and 90) increased significantly (p < 0.05) in the Se-deficient group compare to the corresponding control group. Meanwhile, the protein expression of HSPs (60, 70, and 90) also increased significantly (p < 0.05) in the Se-deficient group. These results suggested that oxidative stress and the levels of HSPs expression levels in chicken liver can be influenced by dietary Se deficiency. And HSPs played an important role in the protection of the liver after oxidative stress due to Se deficiency.

Indirect application of near infrared light induces neuroprotection in a mouse model of parkinsonism - an abscopal neuroprotective effect.

We have previously shown near infrared light (NIr), directed transcranially, mitigates the loss of dopaminergic cells in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice, a model of parkinsonism. These findings complement others suggesting NIr treatment protects against damage from various insults. However one puzzling feature of NIr treatment is that unilateral exposure can lead to a bilateral healing response, suggesting NIr may have 'indirect' protective effects. We investigated whether remote NIr treatment is neuroprotective by administering different MPTP doses (50-, 75-, 100-mg/kg) to mice and treating with 670-nm light directed specifically at either the head or body. Our results show that, despite no direct irradiation of the damaged tissue, remote NIr treatment produces a significant rescue of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta at the milder MPTP dose of 50-mg/kg (∼30% increase vs sham-treated MPTP mice, p<0.05). However this protection did not appear as robust as that achieved by direct irradiation of the head (∼50% increase vs sham-treated MPTP mice, p<0.001). There was no quantifiable protective effect of NIr at higher MPTP doses, irrespective of the delivery mode. Astrocyte and microglia cell numbers in substantia nigra pars compacta were not influenced by either mode of NIr treatment. In summary, the findings suggest that treatment of a remote tissue with NIr is sufficient to induce protection of the brain, reminiscent of the 'abscopal effect' sometimes observed in radiation treatment of metastatic cancer. This discovery has implications for the clinical translation of light-based therapies, providing an improved mode of delivery over transcranial irradiation.

Effects of dietary selenium deficiency on mRNA levels of twenty-one selenoprotein genes in the liver of layer chicken.

Selenium (Se) is an essential trace element in many life forms due to its occurrence as selenocysteine (Sec) residue in selenoproteins. However, little is known about the expression pattern of selenoproteins in the liver of layer chicken. To investigate the effects of Se deficiency on the mRNA expressions of selenoproteins in the liver tissue of layer chickens, 1-day-old layer chickens were randomly allocated into two groups (n=120/group). The Se-deficient group (-Se) was fed a Se-deficient corn-soy basal diet; the Se-adequate group as control (+Se) was fed the same basal diet supplemented with Se at 0.15 mg/kg (sodium selenite). The liver tissue was collected and examined for mRNA levels of 21 selenoprotein genes at 15, 25, 35, 45, 55, and 65 days old. The data indicated that the mRNA expressions of Gpx1, Gpx2, Gpx3, Gpx4, Sepn1, Sepp1, Selo, Sepx1, Selu, Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, SPS2, Selm, SelPb, Sep15, and Sels were decreased (p<0.05), but not the levels of Dio3 and Seli (p>0.05). The results showed that the mRNA levels of 19 selenoprotein (except Seli and Dio3) genes in the layer chicken liver were regulated by diet Se level. The present study provided some compensated data about the roles of Se in the regulation of selenoproteins.

mGlu2/3 agonist-induced hyperthermia: an in vivo assay for detection of mGlu2/3 receptor antagonism and its relation to antidepressant-like efficacy in mice.

An assay to detect the on-target effects of mGlu2/3 receptor antagonists in vivo would be valuable in guiding dosing regimens for the exploration of biological effects of potential therapeutic import. Multiple approaches involving blockade of mGlu2/3 receptor agoinist-driven behavioral effects in mice and rats were investigated. Most of these methods failed to provide a useful method of detection of antagonists in vivo (e.g., locomotor activity). In contrast, the mGlu2/3 receptor agonist LY379268 produced dose-dependent increases in body temperature of mice. The hyperthermic effects of LY379268 was abolished in mGlu2 and in mGlu2/3 receptor null mice but not in mGlu3 null mice. Hyperthermia was not produced by an mGlu8 receptor agonist. Agonist-induced hyperthermia was prevented in a dose-dependent manner by structurally-distinct mGlu2/3 receptor antagonists. The blockade was stereo-specific. Moreover, this biological readout was responsive to both orthosteric and to negative allosteric modulators of mGlu2/3 receptors. Antagonism of agonist-induced hyperthermia predicted antidepressant-like efficacy in the mouse forced swim test. As with the hyperthermic response, the antidepressant-like effects of mGlu2/3 receptor antagonists were shown to be due to mGlu2 and not to mGlu3 or mGlu8 receptors through the use of receptor knock-out mice. The ability to rapidly assess on-target activity of mGlu2/3 receptor antagonists enables determination of parameters for setting efficacy doses in vivo. In turn, efficacy-related data in the preclinical laboratory can help to set expectations of therapeutic potential and dosing in humans.

Two acidic polysaccharides from the flowers of Chrysanthemum morifolium.

Two new acidic polysaccharides, F4 and F5, were isolated from the flowers of Chrysanthemum morifolium. Monosaccharide analysis indicated that F4 contained arabinose, galactose and galacturonic acid units in a molar ratio of 1.0:2.3:6.8 and F5 contained arabinose, rhamnose galactose and galacturonic acid units in a molar ratio of 1.0:3.2:1.0:4.3. The results of methylation analysis, partial acid hydrolysis and NMR spectral analysis indicated that F4 had a homogalacturonan main chain with arabinogalactan side chain linked to 3 position of (1 --> 3,4)-linked galacturonan and F5 had a rhamnogalacturonan main chain with arabinogalactan side chain linked to 3 position of (1 --> 3,4)-linked galacturonan or 4 position of (1 --> 2,4)-linked rhamnose. Biological tests revealed that F4 and F5 could simulate the mitogen induced T and B lymphocyte proliferation in vitro.

[Clinical and experimental study on treatment of moderate and advanced malignant tumors with tianfoshen oral liquid].

OBJECTIVE: To investigate the clinical efficacy of Tianfoshen oral liquid (TFS) in treating moderate and advanced malignant tumors and its mechanism. METHODS: Therapeutic effect of TFS in treating 71 patients of malignant tumor was analyzed with the criteria, including quality of life, 3-year survival rate and immune function. And experimental studies of inhibitory effect on tumor clone primordial cells and tumor growth rate of TFS on human gastric tumor (MGC803) cell, human liver cancer (SMMC7721) cell and mice galactophore cancer (EMT6) cell by colony forming method and dye exclusion test respectively were also conducted. RESULTS: Clinical study showed that in the 71 cases treated, the total remission rate was 45.1%, the effective rate 71.8%, with improvement in quality of life and immune function, the 1-, 2- and 3-year survival rate being 78.5%, 38.5% and 10.8% respectively and the mean survival time 24.2 months. Experimental study showed that TFS could kill the cancer cells directly, inhibit the proliferation of single clonogenic cell, and had a broad-spectrum dose-dependent inhibitory action on various tumors with significant difference in comparing with the effects of the control (P < 0.05). CONCLUSION: TFS had obvious therapeutic effect to moderate and advanced tumors, its anti-tumor effect was related to the enhancement of immune function and tumor inhibiting or direct killing action.

A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway.

The yeast serine/threonine kinase STE20 activates a signaling cascade that includes STE11 (mitogen-activated protein kinase kinase kinase), STE7 (mitogen-activated protein kinase kinase), and FUS3/KSS1 (mitogen-activated protein kinase) in response to signals from both Cdc42 and the heterotrimeric G proteins associated with transmembrane pheromone receptors. Using degenerate polymerase chain reaction, we have isolated a human cDNA encoding a protein kinase homologous to STE20. This protein kinase, designated HPK/GCK-like kinase (HGK), has nucleotide sequences that encode an open reading frame of 1165 amino acids with 11 kinase subdomains. HGK was a serine/threonine protein kinase that specifically activated the c-Jun N-terminal kinase (JNK) signaling pathway when transfected into 293T cells, but it did not stimulate either the extracellular signal-regulated kinase or p38 kinase pathway. HGK also increased AP-1-mediated transcriptional activity in vivo. HGK-induced JNK activation was inhibited by the dominant-negative MKK4 and MKK7 mutants. The dominant-negative mutant of TAK1, but not MEKK1 or MAPK upstream kinase (MUK), strongly inhibited HGK-induced JNK activation. TNF-alpha activated HGK in 293T cells, as well as the dominant-negative HGK mutants, inhibited TNF-alpha-induced JNK activation. These results indicate that HGK, a novel activator of the JNK pathway, may function through TAK1, and that the HGK --> TAK1 --> MKK4, MKK7 --> JNK kinase cascade may mediate the TNF-alpha signaling pathway.

Adeno-associated virus type 2-mediated gene transfer: role of epidermal growth factor receptor protein tyrosine kinase in transgene expression.

Adeno-associated virus type 2 (AAV), a single-stranded, DNA-containing, nonpathogenic human parvovirus, has gained attention as a potentially useful vector for human gene therapy. However, the transduction efficiency of AAV vectors varies greatly in different cells and tissues in vitro and in vivo. We have recently documented that a cellular tyrosine phosphoprotein, designated the single-stranded D-sequence-binding protein (ssD-BP), plays an important role in AAV-mediated transgene expression (K. Y. Qing et al., Proc. Natl. Acad. Sci. USA 94:10879-10884, 1997) and that a strong correlation exists between the phosphorylation state of the ssD-BP and AAV transduction efficiency in vitro as well as in vivo (K. Y. Qing et al., J. Virol. 72:1593-1599, 1998). In this report, we document that treatment of cells with specific inhibitors of the epidermal growth factor receptor protein tyrosine kinase (EGF-R PTK) activity, such as tyrphostin, leads to significant augmentation of AAV transduction efficiency, and phosphorylation of the ssD-BP is mediated by the EGF-R PTK. Treatment of cells with EGF results in phosphorylation of the ssD-BP, whereas treatment with tyrphostin causes dephosphorylation of the ssD-BP and consequently leads to increased expression of the transgene. Furthermore, AAV transduction efficiency inversely correlates with expression of the EGF-R in different cell types, and stable transfection of the EGF-R cDNA causes phosphorylation of the ssD-BP, leading to significant inhibition in AAV-mediated transgene expression which can be overcome by the tyrphostin treatment. These data suggest that the PTK activity of the EGF-R is a crucial determinant in the life cycle of AAV and that further studies on the interaction between the EGF-R and the ssD-BP may yield new insights not only into its role in the host cell but also in the successful use of AAV vectors in human gene therapy.

Molecular cloning and characterization of a novel p38 mitogen-activated protein kinase.

The p38 mitogen-activated protein kinases (MAPK) are activated by cellular stresses and play an important role in regulating gene expression. We have isolated a cDNA encoding a novel protein kinase that has significant homology (57% amino acid identity) to human p38alpha/CSBP. The novel kinase, p38delta, has a nucleotide sequence encoding a protein of 365 amino acids with a putative TGY dual phosphorylation motif. Dot-blot analysis of p38delta mRNA in 50 human tissues revealed a distribution profile of p38delta that differs from p38alpha. p38delta is highly expressed in salivary gland, pituitary gland, and adrenal gland, whereas p38alpha is highly expressed in placenta, cerebellum, bone marrow, thyroid gland, peripheral leukocytes, liver, and spleen. Like p38alpha, p38delta is activated by cellular stress and proinflammatory cytokines. p38delta phosphorylates ATF-2 and PHAS-I, but not MAPK-activated protein kinase-2 and -3, known in vivo and in vitro substrates of p38alpha. We also observed that p38delta was strongly activated by MKK3 and MKK6, while p38alpha was preferentially activated by MKK6. Other experiments showed that a potent p38alpha kinase inhibitor AMG 2372 minimally inhibited the kinase activity of p38delta. Taken together, these data indicate that p38delta is a new member of the p38 MAPK family and that p38delta likely has functions distinct from that of p38alpha.

[Studies on the chemical constituents of Fritillaria in Hubei. X. Isolation and identification of alkaloids from Fritillaria ebeiensis var.purpurea G.D.Yu et P.Li].

The bulb of Fritillaria ebeiensis var. purpurea G.D. Yu et P. Li (Liliaceae) are commercially available as the substitute for the principal Chinese traditional medicine "Beimu". This plant is easily cultivated, has high alkaloid content and conspicuous antitussive and expectorant effects. Seven C-nor-D-homo steroidal alkaloids (I-VII) were isolated from the bulb cultivated in Suizhou district, Hubei. I-IV have been identified as the known alkaloids peimine, peiminine, ebeinine and ebeinone on the basis of spectral data and by TLC and mixed mp comparison with authentic samples. The alkaloid VI, C27H43NO2, mp 186-188 degrees C, named ziebeimine, is a new alkaloid isolated from the title plant. The structure of VI has been established as 5 alpha, 14 alpha-cevanine-13, 17-dehydro-3 alpha, 6 beta-diol on the basis of its IR, 1H-NMR, 13C-NMR and mass spectra. The structure of alkaloids V and VII is still under investigation.