Proteomic study on CUMS-induced senile depression mice's frontal lobe cortex and the regulating effect of KTLD formula.

OBJECTIVE: The aim of this study was to investigate the protein expression of chronic unpredictable mild stress (CUMS)-induced senile depression in SAMP-8 mice's frontal lobe cortex and the regulating effect of the kidney tonifying and liver dispersing (KTLD) formula. MATERIALS AND METHODS: A total of 15 male SAMP-8 mice were randomly divided into control, CUMS, and KTLD groups. CUMS and KTLD mice were subjected to CUMS for 21 days. Control group mice were kept to normal feeding. At the same time as molding, the herbal gavage (KTLD formula, 19.5 g/kg/d) was given from the beginning of the stress stimulation, while the control group and the CUMS group mice were given the same volume of saline for 21 days. Open-field testing (OFT) was used to assess the mice's depression levels. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify differentially expressed proteins (DEPs) in mice's frontal lobe cortex. Bioinformatics analysis including Gene Ontology (GO); Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) networks were utilized to study the DEPs connections. RESULTS: Results revealed that mice with senile depression experienced more anxiety and depression than control mice, whereas KTLD mice had the opposite experience. Biological processes including transport, regulation of transcription, and DNA-templated were identified in both KTLD and CUMS. The KEGG enrichment study of the DEPs in KTLD revealed their involvement in the MAPK signaling pathway, glutamatergic synapse, dopaminergic synapse, axon guidance, and ribosome. KEGG pathway enrichment showed that the mechanism of senile depression and the pathway of KTLD are closely related to axonal conductance and ribosomes. According to the PPI analysis, disease-related proteins regulated by KTLD revealed that some proteins, such as GLOI1 and TRRAP, have potential interactions. This provides fresh insight into how KTLD works to cue senile depression. CONCLUSIONS: KTLD treats senile depression via multiple targets and pathways, which may include regulations of 467 DEPs. Proteomics showed significant changes in protein levels in geriatric depression and after KTLD intervention. Senile depression involves the cross-linking and modulation of signal pathways, presenting a pattern of multiple pathways and multiple targets. According to a protein pathway enrichment and protein interaction model of KTLD in senile depression, KTLD is capable of treating senile depression via multiple pathways and targets.

[A case of bromadiolone poisoning leading to digestive tract, abdominal hemorrhage and secondary paralytic ileus].

Bromadiolone, commonly known as super warfarin, is a long-acting coumarin dicoumarin rodenticide. The mechanism of bromadiolone is mainly to inhibit vitamin K1 epoxide reductase and affect the synthesis of coagulation factors Ⅱ, Ⅶ, Ⅸ and Ⅹ, which causes blood coagulation dysfunction and systemic multiple organ hemorrhage. Here, we report of a case of bromadiolone poisoning patient who had digestive tract, abdominal hemorrhage, as well as secondary paralytic ileus. After blood product transfusion and vitamin K1 supplementation, the patient was discharged after the physical condition was improved. It's suggestied that clinicians should pay attention to rare complications to prevent missed diagnosis when treating other bromadiolone poisoning.

Garlic skin induces shifts in the rumen microbiome and metabolome of fattening lambs.

Garlic (Allium sativum L.) and its constituents have been shown to modify rumen fermentation and improve growth performance. Garlic skin, a by-product of garlic processing, contains similar bioactive components as garlic bulb. This study aimed to investigate the effects of garlic skin supplementation on growth performance, ruminal microbes, and metabolites in ruminants. Twelve Hu lambs were randomly assigned to receive a basal diet (CON) or a basal diet supplemented with 80 g/kg DM of garlic skin (GAS). The experiment lasted for 10 weeks, with the first 2 weeks serving as the adaptation period. The results revealed that the average daily gain and volatile fatty acid concentration were higher (P < 0.05) in lambs fed GAS than those in the CON group. Garlic skin supplementation did not significantly (P > 0.10) affect the α-diversity indices, including the Chao1 index, the abundance-based coverage estimator value, and the Shannon and Simpson indices. At the genus level, garlic skin supplementation altered the ruminal bacterial composition by increasing (P < 0.05) the relative abundances of Prevotella, Bulleidia, Howardella, and Methanosphaera and decreasing (P < 0.05) the abundance of Fretibacterium. Concentrations of 139 metabolites significantly differed (P < 0.05) between the GAS and the CON groups. Among them, substrates for rumen microbial protein synthesis were enriched in the GAS group. The pathways of pyrimidine metabolism, purine metabolism, and vitamin B6 metabolism were influenced (P < 0.05) by garlic skin supplementation. Integrated correlation analysis also provided a link between the significantly altered rumen microbiota and metabolites. Thus, supplementation of garlic skin improved the growth performance of lambs by modifying rumen fermentation through shifts in the rumen microbiome and metabolome.

Use of electroacupuncture to accelerate the antidepressant action of selective serotonin reuptake inhibitors: a single-blind, randomised, controlled study.

1. Patients treated with dense cranial electroacupuncture stimulation (DCEAS) had a significantly greater reduction in the 17-item Hamilton Rating Scale for Depression scores and clinically significant response to treatment than those having sham acupuncture (19.4% vs.8.8%). 2. Neither sham acupuncture nor DCEAS had effects on the platelet serotonin system. 3. In the early phase of selective serotonin reuptake inhibitor treatment for depressed patients, DCEAS could be used as an additional therapy. 4. Neurobiological mechanisms responsible for DCEAS effects warrant further investigation using neuroimaging.

A novel mechanism: Erxian Decoction, a Chinese medicine formula, for relieving menopausal syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Many clinical and experimental reports demonstrated that Erxian Decoction (EXD) was effective in relieving menopausal syndrome. AIM OF THE STUDY: The mechanisms of action of EXD were explored on the endocrine and antioxidant regimen. MATERIALS AND METHODS: Menopause causes a decline in both endocrine function and activities of antioxidant enzymes. In this study, 12-month-old female Sprague-Dawley-rats (SD-rats) with a low serum estradiol level were employed. Their endocrine functions after treatment with EXD were assessed by the determination of their serum estradiol level and ovarian mRNA levels of aromatase, which is a key enzyme for biosynthesis of estradiol. Meanwhile, superoxide dismutase-1 (SOD), catalase (CAT) and glutathione peroxidase (GPx-1) in the liver were also determined to assess the effect of EXD on the antioxidant regimen. RESULTS: Results revealed a significant elevation in serum estradiol level and the mRNA level of ovarian aromatase and liver CAT in the EXD-treated menopausal rat model. CONCLUSIONS: The results obtained from mRNA and estradiol level of the present investigation revealed that the EXD relieves the menopausal syndrome involved an increase of endocrine and antioxidant function through, at least, the activation of aromatase and CAT detoxifying pathways.

Investigation of the neural substrates of voice recognition in Chinese schizophrenic patients with auditory verbal hallucinations: an event-related functional MRI study.

OBJECTIVE: Auditory hallucinations (AVHs), like real auditory perceptions, are often perceived as familiar voices. Given that neural correlates of AVHs involve the auditory cortex, it is likely that those brain regions responsible for recognition of voice identity are invoked during AVHs. METHOD: Schizophrenic patients with (n = 13) and without (n = 13) auditory hallucinations, and 13 healthy subjects performed a voice recognition task during functional magnetic resonance imaging at 1.5 T. In the task using prerecorded vocal stimuli, they classified voice as familiar and unfamiliar. RESULTS: Under the familiar minus unfamiliar contrasts, cerebral activation pattern is different in the three groups and patients with auditory hallucinations showed less activation in the right temporal lobe than controls. CONCLUSION: Voice recognition was impaired in patients with AVHs. Our results support that auditory association cortices play a role in the perception of AVHs.

Effect of total flavonoids of hippophae rhamnoides on contractile mechanics and calcium transfer in stretched myocyte.

OBJECTIVE: To study the role of total flavonoids of hippophae rhamnoides in improving contractile [correction of contactile] function of stretched cardiac myocyte. METHOD: Flavonoids were given to stretched myocytes which were proved their contractile function decline and then myocyte contractile mechanics characteristics and calcium transfer were measured. RESULT: Flavonoids increased myocyte contractility, as indicated by myocyte shortening, velocity of shortening, peak +dL/dt and peak -dL/dt during shortening, in a concentration-dependent manner (r>0.9, P<0.001), and with no relation to the intracellular calcium transfer in the myocytes. CONCLUSION: Flavonoids of the traditional Chinese drug hippophae rhamnoides is effective in improving the contractile function of stretched cardiac myocyte in low dosage.

Selective lesion of the cholinergic basal forebrain causes a loss of cortical neuropeptide Y and somatostatin neurons.

Degeneration of the cholinergic basal forebrain (CBF) and changes in cortical neuropeptide levels have been reported in Alzheimer's disease. In the present study, we sought to determine if a selective cholinergic lesion of nucleus basalis magnocellularis (Nbm) could affect the number and distribution of neuropeptide Y (NPY) and somatostatin (SS) immunoreactive neurons in the frontoparietal and occipital cortices of rats. Brain sections were evaluated at survival times of 1, 2, 4, 8, 12, 24, 48, 78 and 100 weeks after intraventricular injection of 192-saporin, an immunotoxin directed at the low affinity neurotrophin receptor (p75NGFr), that selectively destroys the CBF. Following the immunotoxin lesion of the Nbm, the number of NPY-labeled neurons decreased 33% in the frontoparietal cortex and 60% in the occipital cortex compared to age-matched normal controls at most survival time points. A significant loss of SS-labeled neurons in both cortical regions was seen 12 weeks after 192-saporin injection with no further change up to 100-week survival time. The effect of age on neuropeptidergic populations was evaluated in normal control rats. The number of NPY and SS immunoreactive neurons in aged rats (21-26 months) decreased by 42% in the frontoparietal cortex and 27% in the occipital cortex when compared with young (3-6 months) and middle-age (9-14 months) rats. When both non-lesioned and lesioned animals with different ages were pooled for linear regression, a significant correlation was found between the number of cortical NPY- and SS-labeled neurons and cortical acetylcholinesterase (AChE) histochemical staining intensity. These findings indicate that: (1) cholinergic denervation of the Nbm is associated with an irreversible loss of neocortical NPY and SS immunoreactive neurons analogous to that observed in Alzheimer's disease and aging; (2) the degree of the loss of cortical NPY and SS immunoreactive neurons seems to be related to the extent of the reduction of cortical AChE intensity in both toxin-injected and normal aged rats. These findings may reflect a trophic dependence of NPY and SS neurons on cortical cholinergic input.

[Clinical and experimental studies on elimination of oxygen free radical of jinshuibao capsule in treating senile deficiency syndrome and its deoxyribonucleic acid damage repairing effects].

OBJECTIVE: To observe the efficacy of Jinshuibao capsule. METHODS: Senile patients of Deficiency Syndrome treated with Jinshuibao capsule (JSBC) as treated group and with starch capsule as control group. JSBC is a preparation of Cordyceps sinensis. RESULTS: (1) The superoxide dismutase (SOD) activity in senile patient were markedly lower than that in youth, while the malonyldialdehyde (MDA) level of the former was higher than that of the latter, P < 0.01; (2) The SOD activity increased and the MDA level decreased in the treated group after treatment, P < 0.01. JSBC also revealed satisfactory effect on relieving symptoms such as chilling, dizziness, lassitude in loin and legs, frequent nocturia and tinnitus, etc. Results of animal experiment wese in accordance with that of clinical observation. The unscheduled deoxyribonucleic synthesis (UDS) level of aged group before treatment was obviously lower than that of youth; after treatment, the change was very significant, and the difference between treated group and control group was also very significant (P < 0.01). Animal experiment showed that the sister chromatid exchange (SCE) of splenic cell in young mice group was markedly lower than that in aged mouse group. CONCLUSION: JSBC has not showed the SCE inducting effect, but could accelerate the repairing of damaged deoxyribonucleic acid (DNA).

[Studies on nutritional effects of traditional Chinese tonics with strengthened nutrients on pregnant women and rats].

Clinical and Experimental studies on a mixture made of traditional Chinese tonics (such as Fructus Lycii, Rhizoma Dioscoreae and Arillus Longannae, etc.) and strengthened nutrients (such as iron, zinc and Calcium, etc.) were conducted in order to explore its nutritional and health promoting effects. (1) One hundred and three primiparous women were divided randomly into observed group and control group, results showed that the serum levels of iron, zinc, hemoglobin of observed group were all raised after treatment, these parameters and the concentration of iron in umbilical cord blood as well as body weight of new-born baby of the observed group were higher than that of control group (P < 0.05 or P < 0.01). (2) Results of experimental rats showed that the utilization rate, hemoglobin level, fetal growth and developing parameters of test group were all higher than that of control group significantly (P < 0.05 or P < 0.01). These results suggested that the nutrient mixture has a good nutritional and health promoting effect on pregnancy.

Synergistic inhibitory effects of interferon-alpha and 5-fluorouracil in meningioma cells in vitro.

We have investigated the effects of interferon-alpha (IFN-alpha) and 5-fluorouracil (5-FU) on meningioma cells in two different culture systems, evaluated by the uptake of radiolabelled methionine. With both IFN-alpha and 5-FU an inhibitory effect on the uptake of radiolabelled methionine by the meningioma cells was demonstrated, and we found a synergistic inhibitory effect with a combination of IFN-alpha and 5-FU. To obtain a maximal inhibition of cell metabolism without causing cell toxicity, we were able to decrease the dose of 5-FU by simultaneously adding IFN-alpha. Our results suggest that a combined treatment of IFN-alpha and 5-FU may be a successful alternative for patients with inoperable meningiomas. A novel in vitro positron emission tomography technique was used for the study of metabolic changes in tumour cells caused by drug treatment, which is complementary to conventional cell culture techniques.

[Low-dose of processed rhubarb in preventing pregnancy induced hypertension].

A prospective randomized double blind study with processed rhubarb (low dose of 0.75g/day) was carried out in pregnant women at risk of pregnancy induced hypertension (PIH). Rhubarb (140 cases) or placebo (125 cases) was given to women at risk of PIH consecutively from the 28th week of gestation till delivery, and another 68 pregnant women as control. Results showed that 5.7% of rhubarb treated women developed PIH, a rate substantially lower than the 20.8% of the placebo group (P < 0.01). After 9-10 weeks of treatment, the plasma fibronectin (Fn) level and Plasminogen activator inhibiter (PAI) value were found significantly lower (P < 0.05) in the rhubarb treated group than in the placebo. Antithrombin III (ATIII) level also decreased significantly less in the rhubarb group as compared with the placebo (P < 0.05). It indicated that low dose of processed rhubarb has a good prophylactic effect on PIH. The mechanism may be related with the inhibition of PAI activity, reduced Fn synthesis and decreased damage to vascular endothelium.

K+ currents expressed from the guinea pig cardiac IsK protein are enhanced by activators of protein kinase C.

We have isolated cardiac cDNA and genomic clones encoding the guinea pig IsK protein. The deduced amino acid sequence is approximately 78% identical to the rat, mouse, and human variants of this channel, and the structure of the gene encoding the protein is also similar to that in other species. For example, the gene is present only once in the haploid genome, the protein-coding sequence is present on a single uninterrupted exon, an intron exists in the 5' untranslated domain, and multiple alternative polyadenylation sites are used in processing the transcript. Expression of the guinea pig protein in Xenopus oocytes results in a slowly activating, voltage-dependent K+ current, IsK, similar to those expressed previously from the rat, mouse, and human genes. However, in sharp contrast to the rat and mouse currents, activation of protein kinase C with phorbol esters increases the amplitude of the guinea pig IsK current, analogous to its effects on the endogenous IKs current in guinea pig cardiac myocytes. Mutagenesis of the guinea pig cDNA to alter four cytoplasmic amino acid residues alters the phenotype of the current response to protein kinase C from enhancement to inhibition, mimicking that of rat and mouse IsK currents. This mutation is consistent with reports that phosphorylation of Ser-102 by protein kinase C decreases the current amplitude. These data explain previously reported differences in the regulatory properties between recombinant rat or mouse IsK channels and native guinea pig IKs channels and provide further evidence that the IsK protein forms the channels that underlie the IKs current in the heart.

[Effects of castration and testosterone-replacement on hypothalamic and plasma luteinizing hormone-releasing hormone levels in the aged male rat].

Hypothalamic and plasma luteinizing hormone-releasing hormone (LHRH) levels following orchidectomy (ORDX) and testosterone (T)-replacement were compared between young (2-3 months old) and aged (24-26 months old) male rats by radioimmunoassay. Plasma T level and hypothalamic LHRH content are markedly decreased in the aged rat as compared to those of the young rat, whereas plasma LHRH levels are similar in the two groups. Following ORDX and ORDX plus T-replacement, plasma T levels in both groups are about the same, whereas the rates of variation of hypothalamic and plasma LHRH levels in the aged rat are significantly lower than those in the young rat. These results suggest that the negative feedback mechanism of the hypothalamic LHRHergic system is impaired in the aged rat, which may be one of the important reasons causing age-dependent deterioration of the functional control of hypothalamic-pituitary-testicular axis.