Sex differences in diencephalon serotonin transporter availability in major depression.

BACKGROUND: Major depression is more prevalent in women than men. The present study evaluated if previous findings that demonstrated decreased 5-hydroxytryptamine (5-HT) transporter availability in depressed patients would be confirmed in a larger sample and also evaluated sex differences. METHODS: Depressed (n = 32) and healthy subjects (n = 32), including 16 pairs of women and men, participated in an iodine-123-2 beta-carbomethoxy-3beta-(4-iodophenyltropane) ([(123)I]beta-CIT) single photon emission computed tomography (SPECT) and a magnetic resonance imaging (MRI) scan. Participants were administered [(123)I]beta-CIT (225.7 +/- 3.7 MBq) and imaged 23.0 +/- 1.6 hours later. Statistical analyses included analysis of variance and a regression analysis of the main and interactive effects of age, sex, and depression. RESULTS: Overall, depressed patients demonstrated 12% lower diencephalon and no change in striatal or brainstem [(123)I]beta-CIT uptake. Significant age by sex, sex by depression, and age by sex by depression interactions were noted due to 22% lower diencephalon [(123)I]beta-CIT uptake in depressed women compared with less than a 1% decrease in depressed men. CONCLUSIONS: As observed previously, diencephalon 5-HT transporter availability is decreased in depressed patients. However, the decrease appears to be sex-specific and age-dependent. These findings suggest that serotonergic mechanisms mediating depressed mood differ between men and women in an age-dependent manner and may explain why young women respond better to treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants.     

Electro-acupuncture attenuates stress-induced defecation in rats with chronic visceral hypersensitivity via serotonergic pathway

Acupuncture has long been used for patients with irritable bowel syndrome. However, it has remained unclear. The aim of this study was to testify the effect of electro-acupuncture(EA) on (1) visceral hypersensitivity induced by the mechanical colorectal irritation during postnatal development of rats, and (2) stress-induced colonic motility changes on rats with chronic visceral hypersensitivity. The abdominal withdrawal reflex (pain threshold and score) for visceral hypersensitivity and fecal pellet output for motor dysfunction were selected as two indexes for measurement. In addition, the effect of EA on 5-HT(4a) receptor and serotonin transporter (SERT) expression in the colon mucosa was analyzed semi-quantitatively through immunohistochemistry and 5-HT concentration in the colon tissue was observed through spectro-photo-fluorimeter detection, respectively. Our results showed that EA significantly elevated pain threshold, decreased the scores and also decreased fecal pellet output during water avoid stress. Furthermore, EA decreased 5-HT concentration in colon in rats with CVH and CVH rats with water avoidance stress, and increased the 5-HT(4a) and SERT expression in rats with CVH. Thus, it can be concluded that EA attenuates behavioral hyperalgesia and stress-induced colonic motor dysfunction in CVH rats via serotonergic pathway.     

胰岛素和睾酮对Ishikawa细胞葡萄糖转运蛋白4表达的影响

目的探讨胰岛素(INS)和睾酮(T)对多囊卵巢综合征(PCOS)子宫内膜腺上皮细胞生长的影响和葡萄糖转运蛋白4(GLUT4)表达的调节机制。方法体外培养Ishikawa细胞,予不同浓度INS(90、60、30、3、0.3 U/L)或T(10-3、10-4、10-5、10-6、10-7mmol/ml)刺激Ishikawa细胞48 h,MTT法检测INS、T对Ishikawa细胞生长的作用;免疫细胞化学检测GLUT4蛋白在Ishikawa细胞定位表达;分别以30 U/L INS和10-5mmol/ml T刺激Ishikawa细胞24和48 h,逆转录聚合酶链反应(RT-PCR)方法测定INS和T对Ishikawa细胞GLUT4 mRNA表达的影响。结果(1)不同浓度的INS均可促进Ishikawa细胞的生长,随着INS浓度的增加,INS促进Ishikawa细胞生长作用越强,INS浓度自0.3~30 U/L时,Ishikawa细胞生长依次加强,与对照组相比均有显著性差异(P<0.01)。INS浓度达60、90 U/L时,细胞生长状况与INS浓度为30 U/L相似。不同浓度的T均可抑制Ishikawa细胞的生长,随着T浓度的增加,T抑制Ishikawa细胞生长作用越明显。T浓度自10-7、10-6、10-5mmol/ml,Ishikawa细胞生长依次减弱,与对照组相比均有显著性差异(P<0.01,P<0.05),T浓度达10-4、10-3mmol/ml时,细胞生长抑制状况与T浓度10-5mg/ml相似。(2)GLUT4蛋白,定位表达于Ishikawa细胞的细胞浆内。(3)Ishikawa细胞中GLUT4 mRNA表达,在INS组和T组均较对照组减弱(P<0.01,P<0.05),INS组比T组减弱更明显(P<0.05),且INS和T作用24和48 h GLUT4 mRNA表达无显著性差异(P>0.05)。结论不同浓度INS和T均可影响Ishikawa细胞生长,并降低GLUT4 mRNA的表达,推测PCOS高胰岛素、高雄激素血症的病理生理特性有可能影响子宫内膜的代谢过程,与子宫内膜的病变相关。     

长链非编码RNA-GAS5靶向miR-29下调铜转运蛋白CTR1抑制肾脏纤维化的机制研究

目的研究长链非编码RNA-生长阻滞特异转录物5（GAS5）对肾脏纤维化的作用及机制。方法收集临床肾穿刺患者的组织标本,用原位免疫荧光方法检测GAS5在组织上的定位和表达情况;构建小鼠单侧输尿管梗阻肾脏纤维化模型,用原位免疫荧光方法检测GAS5在肾组织上的定位以及表达情况;用转化生长因子-β（TGF-β）刺激肾小管上皮细胞后,用Real-time PCR方法检测GAS5的表达水平;在肾小管上皮细胞中转染GAS5过表达质粒后,用Western印迹法检测细胞外基质蛋白胶原蛋白3（Col3）、纤连蛋白1（FN1）、铜转运蛋白1（CTR1）和铜离子转运ATP酶α肽（ATP7a）的表达水平,用Real-time PCR方法检测miR-21、miR-29、CTR1和ATP7a的表达。在肾小管上皮细胞中过表达miR-29后,用Western印迹法检测CTR1的表达;在肾小管上皮细胞中过表达miR-21后,用Western印迹法检测ATP7a的表达。结果在不同肾脏纤维化模型中,GAS5均较对照组表达下调。在肾小管上皮细胞中,过表达GAS5抑制Col3和FN1的合成（P<0.05）;过表达GAS5可上调miR-29的表达,并下调miR-21的表达（P<0.05）。miR-29在转录后水平抑制CTR1的蛋白表达（P<0.05）,且过表达GAS5能够降低CTR1的蛋白表达（P<0.05）;miR-21在转录后水平抑制ATP7a的蛋白表达（P<0.05）,但过表达GAS5不影响ATP7a的表达。结论长链非编码RNA-GAS5通过上调miR-29,在转录后水平抑制铜转运蛋白CTR1,进而抑制肾脏纤维化。     

The W258X mutation in SLC22A12 is the predominant cause of Japanese renal hypouricemia

Recently, a urate transporter, hURAT1 (human uric acid transporter 1) encoded by SLC22A12, was isolated from the human kidney. hURAT1 is presumed to play the central role in reabsorption of urate from glomerular filtrate. In the present study, we analyzed SLC22A12 in seven unrelated Japanese patients with renal hypouricemia whose serum level of urate was less than 1.0 mg/dl, and their family members. We performed direct DNA sequencing of the exon and exon-intron boundaries of SLC22A12 using genomic DNA. Six of the seven patients (86%) possess mutations in SLC22A12. In five patients, a homozygous G to A transition at nucleotide 774 within exon 4 of SLC22A12, which forms a stop codon (TGA) at codon 258 (TGG), was identified (W258X). In one patient, the C to T transition within exon 3, which changes threonine at codon 217 to methionine (T217 M), and the W258X mutation were found (compound heterozygote). Thus, among 12 mutational alleles in six patients, 11 were the W258X mutation (92%). Family members with the heterozygous W258X mutation (carriers) show relatively low levels of serum urate. The present study demonstrates that homozygous W258X mutation is the predominant genetic cause of idiopathic renal hypouricemia in Japanese patients.     

骨癌痛小鼠脊髓谷氨酸转运体GLAST表达下调

目的 观察谷氨酸转运体GLAST在骨癌痛小鼠脊髓中表达的变化.方法 35只C3H/HeJ小鼠随机分为2组:骨癌痛组(Ca组,n=30)和假手术组(Sham组,n=5).Ca组小鼠是将含2×105个NCTc2472细胞的20μl的最小必需培养基注入右股骨远端骨髓腔中制备癌痛模型.Sham组是不注射NCTC2472细胞,余操作同于骨癌痛组.Ca组小鼠注射肿瘤细胞后1 d、3 d、7 d、10 d、14 d、21 d观察小鼠的机械缩足阈值(MWT)和热辐射缩足反射潜伏期(PWL),并于注射肿瘤细胞前、注射后7 d、14 d、21 d进行X线检查评估股骨破坏程度.Ca组分别于肿瘤细胞后1 d、3 d、7 d、10 d、14 d、21 d检测行为学实验后处死小鼠取右侧腰段脊髓,Sham组直接取右侧腰段脊髓,采用Western blot方法测定GLAST在脊髓的蛋白表达.结果 Ca组小鼠在接种肿瘤细胞后第7天MWT显著降低,低于术前的基础值(P<0.05),持续下降至第21天;接种后第14天PWL显著降低,低于术前的基础值(P<0.05),持续下降至第21天.ca组小鼠第7天的X线片仅见股骨远端有小的病灶,第14天骨质破坏增多,到第21天骨破坏进一步加重,骨质破坏范围加大,有骨质缺损或骨折出现.Ca组小鼠接种肿瘤细胞后第10天脊髓GLAST蛋白含量开始减少,第14天明显减少,持续降低至术后21 d(P<0.01).结论 骨癌痛小鼠脊髓的谷氨酸转运体GLAST的蛋白表达下降,提示脊髓谷氨酸转运体GLAST参与骨癌痛的形成.     

葡萄糖转运蛋白1在胃癌组织及转移淋巴结中的表达及其与预后的关系

目的 研究葡萄糖转运蛋白1(GLUT1)在胃癌组织及转移淋巴结中的表达特点,探讨其与肿瘤生物学特征和患者预后之间的关系.方法 采用免疫组织化学方法对79例胃癌组织及癌旁正常胃组织GLUT1表达特征进行分析,并分析其预后与GLUT1表达的关系.结果 高、中、低分化腺癌患者GLUT1表达阳性率分别为56.5%、33.3%和36.0%;黏液腺癌和印戒细胞癌GLUT1表达阳性率分别为1/6和7.7%(1/13).GLUT1表达阳性率与肿瘤最大直径(P<0.01)、有无淋巴结转移(P=0.032)和胃癌临床分期(P=0.007)等因素相关.转移淋巴结GLUT1阳性表达率为12.6%.GLUT1阳性组和阴性组1年生存率分别为64.3%和90.2%(P=0.035).结论 GLUT1表达与胃癌的侵袭性指标相关,可能是胃癌预后不良的一个标志.     

Cross-talk between arterioles and tubules in the kidney

In hypertension the pressure natriuresis set point is shifted to a higher pressure due to an increase in both renal vascular resistance and sodium (Na) reabsorption. The afferent arterioles (Af-Arts) and efferent arterioles (Ef-Arts) account for most renal vascular resistance; they control glomerular filtration rate (GFR) and peritubular pressure, and, consequently, renal function. Af-Art and Ef-Art resistance is regulated by factors similar to those in other arterioles and also by tubuloglomerular feedback (TGF). TGF operates via the macula densa, which senses increases in sodium chloride (NaCl) and sends a signal that constricts the Af-Art and dilates the Ef-Art. In the outer renal cortex, the connecting tubule (CNT) returns to the glomerular hilus and contacts the Af-Art. This morphology is compatible with cross-talk between the CNT and Af-Art, so-called connecting tubule glomerular feedback (CTGF). Our studies show that increasing NaCl delivery to the CNT results in Af-Art dilatation that can be blocked by inhibitors of Na transport. We believe cross-talk between the CNT and Af-Art is a novel mechanism that may contribute to regulation of renal blood flow and GFR.     

葡萄糖转运蛋白1在胃癌组织及转移淋巴结中的表达及其与预后的关系

目的 研究葡萄糖转运蛋白1(GLUT1)在胃癌组织及转移淋巴结中的表达特点,探讨其与肿瘤生物学特征和患者预后之间的关系.方法 采用免疫组织化学方法对79例胃癌组织及癌旁正常胃组织GLUT1表达特征进行分析,并分析其预后与GLUT1表达的关系.结果 高、中、低分化腺癌患者GLUT1表达阳性率分别为56.5%、33.3%和36.0%;黏液腺癌和印戒细胞癌GLUT1表达阳性率分别为1/6和7.7%(1/13).GLUT1表达阳性率与肿瘤最大直径(P<0.01)、有无淋巴结转移(P=0.032)和胃癌临床分期(P=0.007)等因素相关.转移淋巴结GLUT1阳性表达率为12.6%.GLUT1阳性组和阴性组1年生存率分别为64.3%和90.2%(P=0.035).结论 GLUT1表达与胃癌的侵袭性指标相关,可能是胃癌预后不良的一个标志.