Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Effects of BCL6 B on proliferation and migration of human colorectal car-cinoma LoVo cells and its potential mechanism / 中国病理生理杂志

AIM:To detect the endogenous expression of B-cell leukemia/lymphoma 6 member B (BCL6B) in FHC and LoVo cells, and to investigate the effects of BCL6B on proliferation and migration of LoVo cells for further explo-ring the underlying mechanism .METHODS:The endogenous expression of BCL 6B in the FHC and LoVo cells was detec-ted by RT-PCR and Western blot .The methods of MTT assay , colony formation assay , wound healing assay and Transwell chamber experiment were employed to examine the biological functions of BCL 6B in the LoVo cells.The mRNA and protein levels of BCL6B, cyclin D1 and matrix metalloproteinase-9 ( MMP-9) were determined by RT-PCR and Western blot , re-spectively.The level of phosphorylated protein kinase B (p-AKT) was detected by Western blot.RESULTS:BCL6B ex-pression was notably repressed in the LoVo cells as compared with the FHC cells , which were significantly increased by transfection with pcDNA3.1-BCL6B.The abilities of proliferation and migration of the LoVo cells at 72 h were inhibited by 28.33%(P<0.01) and 36.11%(P<0.05) in BCL6B group.The mRNA levels of cyclin D1 and MMP-9 in the cells of BCL6B group were decreased by 39.90%(P<0.01) and 77.36% (P <0.05), and the protein levels of cyclin D1, MMP-9 and p-AKT were reduced by 44.00%(P<0.05), 47.06%(P<0.01) and 32.88% (P<0.05), respectively. CONCLUSION:BCL6B inhibits proliferation and migration of the LoVo cells , and the PI3K/AKT signaling pathway is in-volved in this process .

Epidemiology of thyroid nodules and thyroid function in southern mountainous areas of Ningxia Hui Autonomous Region / 中华健康管理学杂志

Objective To investigate the prevalence of thyroid nodules and thyroid dysfunction in southern mountainouss areas of Ningxia.Methods A cross-sectional study was conducted among a representative sample of 10 639 adults in Jingyuan county with a population proportionate sampling method.High-resolution ultrasound was used to examine the thyroid and fasting blood specimens were collected in the morning for measurement of TSH,FT4,FT3.Chi-square test and spearman rank correlation analysis were used for statistical analysis.Results The prevalence of thyroid nodules was 29.08％,the sex-and age-adjusted rate was 27.17％.The prevalence of thyroid nodules was higher in women than in men (32.68％ vs.24.88％,x2=76.029 2,P＜0.001) and age was positively associated with thyroid nodules (r=0.272,P＜0.001).The rate of thyroid dysfunetion,subclinical hypothyroidism,subclinical hyperthyroidism,hypothyroidism,hyperthyroidism were 17.39％,13.00％,0.42％,0.96％,3.01％,respectively.The prevalence of thyroid nodules was higher in abnormal TSH group than in normal TSH group (39.44％ vs.27.24％,x2=95.624 0,P＜0.001).The level of THS,FT3,FT4 in thyroid nodules group differed fromn control group (Z=-9.144,P＜0.001;Z=-6.140,P＜0.001;Z=-1.997,P=0.046).Conclusion The prevalence of thyroid nodules and thyroid dysfunction were higher in southern mountainous areas of Ningxia.The relationship between thyroid nodules and thyroid function needs further research.We should pay attention to the early screening and diagnosis of thyroid nodules in mountainous areas.

High-intensity focused ultrasound inhibits tumor metastasis in a melanoma-bearing mouse model / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of high-intensity focused ultrasound (HIFU) on tumor metastasis in mouse model bearing melanoma xenograft.</p><p><b>METHODS</b>Mice bearing murine melanoma B16-F10 cell xenograft were randomized for sham-HIFU or HIFU exposure when the tumors grew to a maximum diameter of 7-10 mm, and the tumor size was measured every 3 days. The cumulative survival rate of the mice and tumor metastasis rate were calculated, and the circulating melanoma cells were detected using qRT-PCR. At 14 days after HIFU treatment, B16-F10 cells were retransplanted via the tail vein and the pulmonary metastatic nodules were counted.</p><p><b>RESULTS</b>The median survival time of the mice was 19.00 days (95% CI 17.14-20.86 days) in the sham group and 26.00 days (95%CI 24.76-27.25 days) in HIFU group. The cumulative survival rate in the HIFU group was significantly higher than that in sham-HIFU group (P<0.01), and the tumor size was significantly smaller in HIFU group at 20, 23, and 26 days after HIFU treatment (P<0.05). Compared with the sham-HIFU group, HIFU group had significantly lower levels of MAGE-A3, MART1 and PAX3 at 7 days after HIFU (P<0.05) with still lower MAGE-A3 level at 14 days (P<0.05). HIFU group showed a significantly smaller number of pulmonary metastatic nodules following tumor cell retransplantation than in sham-HIFU group (P<0.01) with a metastasis inhibition rate of 42.4%.</p><p><b>CONCLUSION</b>HIFU treatment can inhibit tumor metastasis in melanoma-bearing mice possibly by reducing tumor cell detachment from the primary tumor site and suppressing colonization of the circulating melanoma cells.</p>

Study on Conversion of Conjugated Anthraquinone in Radix et Rhizoma Rhei by Yeast Strain / 世界科学技术-中医药现代化

A yeast strain KM12 , which can convert conjugated anthraquinone of rhub arb to free anthraquinone , was screened. And it is identified as Kluyveromyces marxianus by 26S rDNA. The percentage of free an-thraquinone in total anthraquinone of rhub arb as an indicator was used to investigate the effect of culture medium component and fermentation processing conditions, such as seed age, fermentation time and liquid volume on con-version of conjugated anthraquinone by KM12. The optimal fermentation medium was determined by orthogonal test L9(43) and the composition (%) is yeast extract 1, glucose 2, and rhubarb 2. The 5% (V/V) of the seed culture inoculated 36-48 h was inoculumed to fermentation medium in shake flask to ferment at 30℃, 200 r?min-1 for 4 days. TLC analysis showed most of conjugated anthraquinone decomposed or converted into free anthraquinone in fermented rhub arb . It was concluded that the side effect of severe diarrhea caused by Chinese medicine rhub arb can be alleviated through fermentation processing by KM12 strain .

Construction and expression of traceable DNA vaccine for prevention of caries / 华西口腔医学杂志

<p><b>OBJECTIVE</b>Streptococcus mutans has been proved as a causative bacteria of human dental caries. The surface protein antigen is one of the important pathogenic factors. The A region of the surface protein antigen pac gene (pacA) can enrich T-cells and B-cells epitope. In this study, a DNA vaccine carrying pacA and gfp gene (a reporter gene) for caries prevention was constructed. The DNA vaccine was liable to be traced in vitro and in vivo.</p><p><b>METHODS</b>The fragment of pacA (1.3 kb) was amplified by PCR with the plasmid pPC41 as template, and inserted into a pEGFP-C1 vector. The recombinant plasmid produced was named as pEGFPC1-pacA. After the COS1 cell line was transfected by the recombinant plasmid, the expression of gfp was detected by observing the green fluorescence and measuring the fluorescence intensity, and the expression of pacA was detected by RT-PCR.</p><p><b>RESULTS</b>Restricted analyzing, sequencing and PCR technique were employed to identify the recombinant plasmid. The phase and orientation of the pacA gene inserted into the vector pEGFPC1 were correct and no changes of their open reading frames were discovered. The transfected COS1 carrying green fluorescent protein (GFP) was observed; the GFP expression level of transfected cells was higher than that of controlled cell. The transcript of pacA gene was confirmed by RT-PCR.</p><p><b>CONCLUSION</b>Construction of the recombinant plasmid was successful. The gfp gene and pacA gene in the plasmid was transcribed and expressed simultaneously in the transfected cells. Moreover, detection of GFP is simple, safe and effective for living cells.</p>

IDENTIFICATION OF HUMAN PAPILLOMAVIRUSES DNA IN LESIONS FROM WOMEN WITH CONDYLOMA ACUMINATA BY MOLECULAR HYBRIDIZATION / 西安交通大学学报(医学版)

HPV DNA were detected in 60 biopsies from women with condyloma acuminata (vulva 47,Vagina 12,cervix 1)by dot blot hybridiztion;physical states of 8 HPV 11 DNA were analyzed by techniques of restriction endonuclease and Southern blot hybridization. HPV 11 was found in 19biopsies of vulva (13 ). vagina (5)and cervix (1),and HPV 16 and 18 in lvaginal and 1 vulvar biopsy respectively. All of HPV 11 DNA were episomal in cells . Our results provided the data for further studying the relationship between HPV and genital cancer in our country.