Korean red ginseng alleviate depressive disorder by improving astrocyte gap junction function.

ETHNOPHARMACOLOGICAL RELEVANCE: Korean red ginseng (KRG), a processed product of Panax ginseng C. A. Mey, show significant anti-depressive effect in clinic. However, its mechanism is still unclear. AIM OF THE STUDY: Gap junction intercellular communication (GJIC) dysfunction is a potential pathogenesis of depression. Therefore, this study's objective is to investigate whether the antidepressant effect of KRG is related to GJIC. MATERIALS AND METHODS: Rat were restraint 8 h every day for 28 consecutive days to prepare depression models, and meanwhile, rats were intragastrically administrated with normal saline, KRG solutions (25, 50 or 100 mg/kg) or fluoxetine (10 mg/kg) 1 h before stress. The behavioral performance was determined by forced swimming test, sucrose preference test and open field test. GJIC was determined by the Lucifer yellow (LY) diffusion distance in prelimb cortex (PLC). In addition, the level of Cx43, one of executors of GJIC, was tested by Western blot. To find out the protective effect of KRG against GJIC dysfunction directly, rats were intracranially injected with carbenoxolone (CBX, blocker of GJIC), and meanwhile normal saline, KRG (100 mg/kg) or fluoxetine (10 mg/kg) was administered daily. The behavioral performance of these rats was detected, and the LY localization injection PLC area was used to detect the gap junction function. RESULTS: Chronic resistant stress (CRS) induced depressive symptoms, as manifested by prolonged immobility time in forced swimming test and decreased sucrose consumption ratio. Administration of KRG alleviated these depressive symptoms significantly. GJIC determination showed that KRG improved the LY diffusion and increased Cx43 level in prefrontal cortex (PFC) significantly, indicated that GJIC dysfunction was alleviated by the treatment of KRG. However, the astrocytes number was also increased by the treatment of KRG, which maybe alleviate depression-like symptoms by increasing the number of astrocytes rather than improving GJIC. Injection of CBX produced depressive symptoms and GJIC dysfunction, as manifested by decreased sucrose consumption ratio and prolonged immobility time in forced swimming test, but no astrocytes number changes, KRG also reversed depressive symptoms and GJIC dysfunction, suggested that the improvement of depressive-like symptoms was improved by GJIC. CONCLUSIONS: KRG alleviate depressive disorder by improving astrocytic gap junction function.

Complete mitochondrial genome of a potential vector louse fly, Lipoptena grahami (Diptera, Hippoboscidae).

Lipoptena grahami Bequaert, 1942 (Diptera, Hippoboscidae) was first described in China almost 80 years ago. Species of Lipoptena were obligate blooding-feeding insects and commonly reported as vectors of wild animals of Cervinae. The complete mitochondrial genome of L. grahami was assembled to 16,953 bp in length. The AT content of L. grahami mitogenome is 80.59%. In total, 22 tRNAs, 2 rRNAs, and 13 protein-coding genes (PCGs) were annotated from L. grahami's mitogenome. The typical clover-leaf structure of tRNAs was also analyzed and confirmed except the tRNA-Ser (AGN). A phylogenetic tree was constructed based on L. grahami with some other fly species.

Exogenous Adenosine Antagonizes Excitatory Amino Acid Toxicity in Primary Astrocytes.

Excitatory toxicity is still a hot topic in the study of ischemic stroke, and related research has focused mainly on neurons. Adenosine is an important neuromodulator that is known as a "biosignature" in the central nervous system (CNS). The protective effect of exogenous adenosine on neurons has been confirmed, but its mechanism remains elusive. In this study, astrocytes were pretreated with adenosine, and the effects of an A2a receptor (A2aR) inhibitor (SCH58261) and A2b receptor (A2bR) inhibitor (PSB1115) on excitatory glutamate were investigated. An oxygen glucose deprivation/reoxygenation (OGD/R) and glutamate model was generated in vitro. Post-model assessment included expression levels of glutamate transporters (glt-1), gap junction protein (Cx43) and glutamate receptor (AMPAR), Na+-K+-ATPase activity, and diffusion distance of dyes. Glutamate and glutamine contents were determined at different time points. The results showed that (1) adenosine could improve the function of Na+-K+-ATPase, upregulate the expression of glt-1, and enhance the synthesis of glutamine in astrocytes. This effect was associated with A2aR activation but not with A2bR activation. (2) Adenosine could inhibit the expression of gap junction protein (Cx43) and reduce glutamate diffusion. Inhibition of A2aR attenuated adenosine inhibition of gap junction intercellular communication (GJIC) in the OGD/R model, while it enhanced adenosine inhibition of GJIC in the glutamate model, depending on the glutamate concentration. (3) Adenosine could cause AMPAR gradually entered the nucleus from the cytoplasm, thereby reducing the expression of AMPAR on the cell membrane. Taken together, the results indicate that adenosine plays a role of anti-excitatory toxicity effect in protection against neuronal death and the functional recovery of ischemic stroke mainly by targeting astrocytes, which are closely related to A2aR. The present study provided a scientific basis for adenosine prevention and ischemic stroke treatment, thereby providing a new approach for alleviating ischemic stroke.

Human CD133-positive hematopoietic progenitor cells enhance the malignancy of breast cancer cells.

BACKGROUND: Human CD133+ hematopoietic progenitor cells (HPCs) are a specific subset of cells that can regulate tumor malignancy. However, the mechanism by which CD133+ HPCs affect the malignancy of human breast cancer has not been reported. METHODS: CD133+ HPCs were isolated and purified from human umbilical cord blood (UCB). We used in vitro culture of MCF-7 and MDA-MB-231 cell lines, and MCF-7 and MDA-MB-231 cells in nude mice to evaluate whether CD133+ HPCs affected the apoptosis, proliferation, invasion and epithelial mesenchymal transition EMT of breast cancer cells. RESULTS: Co-culture with CD133+ HPCs, but not UCB CD133- cells, promoted the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells, accompanied by reducing in vitro spontaneous apoptosis. Co-administration of these two lines with CD133+ HPCs significantly enhanced the growth of implanted breast cancer in vivo. Furthermore, co-culture with CD133+ HPCs, enhanced the invasion of breast cancer cells, N-cadherin and Vimentin expression, but reduced E-cadherin expression in breast cancer cells. CONCLUSIONS: Our study demonstrated that CD133+ HPCs enhance the malignancy of breast cancer cells by attenuating spontaneous apoptosis and promoting the process of epithelial mesenchymal transition. These findings may provide new insights into the role of human CD133+ HPCs in breast cancer pathogenesis. Therefore, CD133+ HPCs may be a new therapeutic target for inhibiting the progression of breast cancer.

[Expression of 17 beta-hydroxysteroid dehydrogenase type 1 in the kidney of rats: the capacity of the kidney for synthesizing sex hormones].

OBJECTIVE: To investigate the expression of 17 beta-hydroxysteroid dehydrogenase type 1 (17ß-HSD1) in the kidney of rats and explore the capacity of the kidney for synthesizing sex hormones. METHODS: The expressions of 17-HSD1 and sex hormones were detected by Western blotting and radioimmunoassay in rat renal cells in primary cultured for 24 and 48 h in the presence or absence of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). RESULTS: After cell culture for 24 h, the primary rat renal cells expressed a low level of 17ß-HSD1 (0.1843±0.076), which increased to 1.6651±0.044 (P<0.01) in response to co-stimulation by FSH and LH. Low levels of estradiol, progesterone and testosterone were also detected in rat renal cells (3.30±3.78, 62.60±12.33, and 22.12±3.36, respectively), and co-stimulation of FSH and LH significantly increased their levels to 8.50±2.64, 117.80±9.79, and 45.04±4.39, respectively (P<0.05). The levels of these hormones showed no significant differences between cells cultured for 24 h and 48 h (P>0.05). CONCLUSION: The rat renal cells express 17ß-HSD1 and are capable of stably secreting sex hormones in response to co-stimulation with FSH and LH, suggesting the capacity of the rat kidneys for synthesizing sex hormones. These findings enrich the understanding of the endocrine function of the kidney.

[Effects of bushen jiannao recipe on the content of acetylcholine and the hippocampal ERK1 and ERK2 protein expressions of vascular dementia rats].

OBJECTIVE: To explore the effects of Bushen Jiannao Recipe (BJR) on the content of acetylcholine (Ach) and ERK1 and ERK2 protein expressions in the hippocampal CA1 region of vascular dementia (VD) rats, and to explore its possible mechanisms for treating VD. METHODS: Eighty-three rats were selected. The VD model was established by permanent bilateral occlusion of both common carotid arteries (2-VO). Then the modeled rats were randomly divided into 5 groups, i. e., the memory deficit model group, the donepezil group, and the positive drug control groups [including high (n = 13), middle (n = 13), and low (n = 12) dose BJR group]. Besides, another 13 rats were chosen as the sham-operative group. The distilled water was given by gastrogavage to rats in the sham-operative group and the memory deficit model group (5 mL/kg). The donepezil hydrochloride suspension was given to rats in the donepezil group by gastrogavage (0.52 mg/kg). High (56 g/kg), middle (28 g/kg), and low (14 g/kg) dose of BJR were respectively given to rats in the other three groups. After 30 days of intervention, the escape latency period and platform crossing times were determined using Morris water maze experiment. The contents of Ach in the hippocampus and cortex were determined using colorimetry. The expressions of ERK1 and ERK2 in the CA1 region of the hippocampus were detected using immunohistochemical assay. RESULTS: The average escape latency of intervened rats showed an overall decreasing trend. From the third to the fifth day, the escape latency period was prolonged, the platform crossing times were reduced, the contents of Ach in the cortex and the hippocampus were lowered, the numbers of positive stained neuron of ERK1 and ERK2 in the hippocampus CA1 region were reduced, showing statistical difference when compared with the sham-operative group (P<0.01). Compared with the model group, the 4th day escape latency of the donepezil group and the high dose BJR group was shortened. The escape latency was shortened, and the platform crossing times, and the numbers of positive stained neuron of ERK1 and ERK2 in hippocampus CA1 region increased on the fifth day. The contents of Ach in the cortex and the hippocampus increased with statistical difference (P<0.05). Compared with the low dose BJR group, the 4th- and 5th-day latency period were shortened, the positive numbers of ERK1 and ERK2 in the hippocampus CA1 region increased in the high dose BJR group with statistical difference (P<0.05). Compared with the donepezil group, the Ach content in the cortex and the hippocampus of the middle and low dose BJR groups decreased (P<0.05). CONCLUSIONS: BJR could obviously improve the function of learning and memory of VD rats. Its mechanisms might be associated with its actions in enhancing Ach contents of the cortex and the hippocampus, and promoting the protein expressions of ERK1 and ERK2 in the hippocampus CA1 region.

[Effects of fetal renal cell suspension on free radicals in ovariectomized rats].

OBJECTIVE: To observe the changes of free radicals in rats after ovariectomy and the intervention effect of fetal renal cell suspension (FRCS) on them. METHODS: Totally 48 Sprague-Dawley rats, eight in the normal control group were sham-operated and treated with saline; the other 40 were ovariectomized and randomly divided into four groups: the model control group (A) administered with normal saline, the positive control group (B) administered with nilestriol, the two testing groups (C and D) administered respectively with living and dead FRCS. The administration was beginning from 12 weeks after operation and lasted for four weeks. Levels of serum superoxide dismutase (SOD) and nitric monoxide synthase (NOS) activity, malondialdehyde (MDA) and nitric oxide (NO) contents were measured at the terminal of the study. RESULTS: Compared with the sham-operated group, levels of SOD, NOS and NO in Group A were significantly lower, while level of MDA was significantly higher (P < 0.01). Compared with Group A, all above-mentioned abnormalities of indices were inversely changed in the three intervened groups significantly (P < 0.05 or P < 0.01), but showed insignificant difference in the paired comparisons of the three groups (P > 0.05). CONCLUSION: High free radical condition is surely present in ovariectomized rats, FRCS can lessen the injury of free radicals and enhance the oxidation antagonizing capacity of the organism.

[Study on treatment of early onset of severe pre-eclampsia by salviae injection and ligustrazine injection in combining with Western medicine].

OBJECTIVE: To evaluate the efficacy of Salviae injection and ligustrazine injection (S & L) in combining with Western medicine for treatment of early onset of severe pre-eclampsia (EOSP), and its impact on pregnancy. METHODS: An open prospective controlled study was conducted on 63 women suffering from EOSP during the 29th-32th week of pregnancy. They were assigned, according to the sequence of hospitalizing, to the treated group (32 cases) and the control group (31 cases). Both groups were treated with conventional Western medical treatment, but S & L were administered additionally to the treated group. Levels of plasma D-dimer, blood viscosity, and outcome of the pregnancy were analyzed. RESULTS: The effect in prolonging the pregnancy and lowing the incidence of fetal distress and newborn death in the treated group was superior to that in the control group, the corresponding data were 11.0 +/- 1.2 days, 11 cases, 4 cases in the treated group and 6.0 +/- 1.5 days, 16 cases and 8 cases in the control group, respectively. Levels of blood viscosity ratio and D-dimer in the treated group were lowered significantly after treatment (1.20 +/- 0.13 vs 2.29 +/- 0.13, 1.61 +/- 0.45 mg/L vs 2.40 +/- 0.09 mg/L), which had no remarkable change in the control group. CONCLUSION: Combined application of S & L for treatment of EOSP could improve the blood hyperviscosity, prolong the pregnancy week, and improve the outcome of pregnancy to reduce incidence of perinatal morbidity and mortality in patients.