Do vegetarians have a normal bone mass?

Public health strategies targeting the prevention of poor bone health on a population-wide basis are urgently required, with particular emphasis being placed on modifiable factors such as nutrition. The aim of this review was to assess the impact of a vegetarian diet on indices of skeletal integrity to address specifically whether vegetarians have a normal bone mass. Analysis of existing literature, through a combination of observational, clinical and intervention studies were assessed in relation to bone health for the following: lacto-ovo-vegetarian and vegan diets versus omnivorous, predominantly meat diets, consumption of animal versus vegetable protein, and fruit and vegetable consumption. Mechanisms of action for a dietary component effect were examined and other potential dietary differences between vegetarians and non-vegetarians were also explored. Key findings included: (i) no differences in bone health indices between lacto-ovo-vegetarians and omnivores; (ii) conflicting data for protein effects on bone with high protein consumption (particularly without supporting calcium/alkali intakes) and low protein intake (particularly with respect to vegan diets) being detrimental to the skeleton; (iii) growing support for a beneficial effect of fruit and vegetable intake on bone, with mechanisms of action currently remaining unclarified. The impact of a vegetarian diet on bone health is a hugely complex area since: 1) components of the diet (such as calcium, protein, alkali, vitamin K, phytoestrogens) may be varied; 2) key lifestyle factors which are important to bone (such as physical activity) may be different; 3) the tools available for assessing consumption of food are relatively weak. However, from data available and given the limitations stipulated above, vegetarians do certainly appear to have normal bone mass. What remains our challenge is to determine what components of a vegetarian diet are of particular benefit to bone, at what levels and under which mechanisms.     

Bcl-2、 cyclin A2和P13K在激素受体阴性乳腺癌中的表达及意义

目的探讨激素受体阴性乳腺癌中B淋巴细胞瘤／白血病2基因（ B-cell lymphoma/leukemia-2, Bcl-2 ）、细胞周期素A2（cyclinA2）和磷酸肌醇3激酶（ phosphoinositide 3 -kinase, PI3K ）的表达及意义。方法采用实时聚合酶链反应（real time polymerase chain reaction,RT-PCR）方法检测Bcl-2、cyclinA2和P13K在激素受体阴性乳腺癌组织（58例）、乳腺正常组织（14例）中的表达水平,并采用Mann-WhitneyU检验分析其与临床病理特征的关系。结果与乳腺正常组织相比,激素受体阴性乳腺癌中Bel-2表达降低,而cyclinA2和P13K表达增高（P〈0．05）。在乳腺癌组织中,Bcl-2在TNM分期Ⅲ期、组织学分级Ⅲ级和出现转移复发的患者中表达水平降低（P〈0．05）,但其表达在不同年龄、肿瘤大小和淋巴结转移的组间差异无显著性（P〉0．05）;cyclinA2在转移复发的患者中显著高表达（P〈0．05）,但在不同的年龄、肿瘤大小、组织学分级、TNM分期和淋巴结状态的组间差异均无显著性（P〉0．05）;P13K在有淋巴结转移和TNM分期Ⅲ期的患者中高表达（P〈0．05）,但其表达在不同年龄、肿瘤大小、组织学分级以及是否转移复发的组间差异均无显著性（P〉0．05）。结论Bcl-2低表达、eyclinA2和P13K高表达可能与激素受体阴性乳腺癌的发生发展有关。     

Elastolytic activity in women with stress urinary incontinence and pelvic organ prolapse

AIMS: Weakening of pelvic supportive tissues is thought to be a contributing etiology in female pelvic floor disorders such as stress urinary incontinence and/or pelvic organ prolapse (SUI/POP). Since elastin modulates the mechanical properties of supportive tissues, we examined elastase activity in vaginal tissue from women with pelvic floor dysfunction compared to asymptomatic controls, by comparing overall elastase activity, human neutrophil elastase, cathepsin K, and alpha-1 antitrypsin (a serine protease inhibitor) mRNA and protein levels. METHODS: Full-thickness peri-urethral vaginal wall tissues were collected from age and menstrual-phase matched SUI/POP and control women at the time of pelvic surgery. Elastolytic activity in the homogenized tissue was determined by the generation of amino groups from succinylated elastin. To quantify mRNA levels of each protein, quantitative competitive-PCR and confirmatory Western blot analyses were performed on the samples for human neutrophil elastase, cathepsin K, and alpha-1 antitrypsin. RESULTS: The mean elastolytic activity in vaginal tissues from the SUI/POP group was similar to that in the control group. With respect to the proteolytic enzymes, neither human neutrophil elastase nor cathepsin K differed between the two groups. However, alpha-1 antitrypsin mRNA and protein levels were significantly decreased in tissues from affected women. CONCLUSIONS: A significant decrease in alpha-1 antitrypsin expression was seen in tissues from women with SUI/POP compared to controls. This data suggest that altered elastin metabolism may contribute to the connective tissue alterations observed in pelvic floor dysfunction. Future investigations are warranted to help define the role of elastin turnover in pelvic floor dysfunction.     

Large-conductance Ca2+-activated K+ channel involvement in suppression of cerebral ischemia/reperfusion injury after electroacupuncture atShuigou (GV26) acupoint in rats

Excess activation and expression of large-conductance Ca2+-activated K+ channels (BKCa channels) may be an important mechanism for delayed neuronal death after cerebral ischemia/reperfusion injury. Electroacupuncture can regulate BKCa channels after cerebral ischemia/reperfusion injury, but the precise mechanism remains unclear. In this study, we established a rat model of cerebral ischemia/reperfusion injury. Model rats received electroacupuncture of 1 mA and 2 Hz atShuigou (GV26) for 10 minutes, once every 12 hours for a total of six times in 72 hours. We found that in cerebral ischemia/reperfusion injury rats, ischemic changes in the cerebral cortex were mitigated after electroacupuncture. Moreover, BKCa channel protein and mRNA expression were reduced in the cerebral cortex and neurological function noticeably improved. These changes did not occur after electroacupuncture at a non-acupoint (5 mm lateral to the left side of Shuigou). Thus, our ifndings indicate that electroacupuncture atShuigou improves neurological function in rats following cerebral ischemia/reperfu-sion injury, and may be associated with down-regulation of BKCa channel protein and mRNA expression. Additionally, our results suggest that theShuigou acupoint has functional speciifcity.     

Gain Modulation of Cholinergic Neurons in the Medial Septum‐Diagonal Band of Broca Through Hyperpolarization

Hippocampal network oscillations are important for learning and memory. Theta rhythms are involved in attention, navigation, and memory encoding, whereas sharp wave‐ripple complexes are involved in memory consolidation. Cholinergic neurons in the medial septum‐diagonal band of Broca (MS‐DB) influence both types of hippocampal oscillations, promoting theta rhythms and suppressing sharp wave‐ripples. They also receive frequency‐dependent hyperpolarizing feedback from hippocamposeptal connections, potentially affecting their role as neuromodulators in the septohippocampal circuit. However, little is known about how the integration properties of cholinergic MS‐DB neurons change with hyperpolarization. By potentially altering firing behavior in cholinergic neurons, hyperpolarizing feedback from the hippocampal neurons may, in turn, change hippocampal network activity. To study changes in membrane integration properties in cholinergic neurons in response to hyperpolarizing inputs, we used whole‐cell patch‐clamp recordings targeting genetically labeled, choline acetyltransferase‐positive neurons in mouse brain slices. Hyperpolarization of cholinergic MS‐DB neurons resulted in a long‐lasting decrease in spike firing rate and input‐output gain. Additionally, voltage‐clamp measures implicated a slowly inactivating, 4‐AP‐insensitive, outward K⁺ conductance. Using a conductance‐based model of cholinergic MS‐DB neurons, we show that the ability of this conductance to modulate firing rate and gain depends on the expression of an experimentally verified shallow intrinsic spike frequency‐voltage relationship. Together, these findings point to a means through which negative feedback from hippocampal neurons can influence the role of cholinergic MS‐DB neurons. © 2016 Wiley Periodicals, Inc.     

Serotonin 5‐HT1B receptor‐mediated calcium influx‐independent presynaptic inhibition of GABA release onto rat basal forebrain cholinergic neurons

Modulatory roles of serotonin (5‐HT) in GABAergic transmission onto basal forebrain cholinergic neurons were investigated, using whole‐cell patch‐clamp technique in the rat brain slices. GABA_A receptor‐mediated inhibitory postsynaptic currents (IPSCs) were evoked by focal stimulation. Bath application of 5‐HT (0.1–300 μm ) reversibly suppressed the amplitude of evoked IPSCs in a concentration‐dependent manner. Application of a 5‐HT_1B receptor agonist, CP93129, also suppressed the evoked IPSCs, whereas a 5‐HT_1A receptor agonist, 8‐OH‐DPAT had little effect on the evoked IPSCs amplitude. In the presence of NAS‐181, a 5‐HT_1B receptor antagonist, 5‐HT‐induced suppression of evoked IPSCs was antagonised, whereas NAN‐190, a 5‐HT_1A receptor antagonist did not antagonise the 5‐HT‐induced suppression of evoked IPSCs. Bath application of 5‐HT reduced the frequency of spontaneous miniature IPSCs without changing their amplitude distribution. The effect of 5‐HT on miniature IPSCs remained unchanged when extracellular Ca²⁺ was replaced by Mg²⁺. The paired‐pulse ratio was increased by CP93129. In the presence of ω‐CgTX, the N‐type Ca²⁺ channel blocker, ω‐Aga‐TK, the P/Q‐type Ca²⁺ channel blocker, or SNX‐482, the R‐type Ca²⁺ channel blocker, 5‐HT could still inhibit the evoked IPSCs. 4‐AP, a K⁺ channel blocker, enhanced the evoked IPSCs, and CP93129 had no longer inhibitory effect in the presence of 4‐AP. CP93129 increased the number of action potentials elicited by depolarising current pulses. These results suggest that activation of presynaptic 5‐HT_1B receptors on the terminals of GABAergic afferents to basal forebrain cholinergic neurons inhibits GABA release in Ca²⁺ influx‐independent manner by modulation of K⁺ channels, leading to enhancement of neuronal activities.     

Common epigenetic variation in a European population of mentally healthy young adults

DNA methylation represents an important link between structural genetic variation and complex phenotypes. The study of genome-wide CpG methylation and its relation to traits relevant to psychiatry has become increasingly important. Here, we analyzed quality metrics of 394,043 CpG sites in two samples of 568 and 319 mentally healthy young adults. For 25% of all CpGs we observed medium to large common epigenetic variation. These CpGs were overrepresented in open sea and shore regions, as well as in intergenic regions. They also showed a strong enrichment of significant hits in association analyses. Furthermore, a significant proportion of common DNA methylation is at least partially genetically driven and thus may be observed similarly across tissues. These findings could be of particular relevance for studies of complex neuropsychiatric traits, which often rely on proxy tissues.     

白藜芦醇通过激活PI3K/Akt信号通路减轻大鼠脑缺血再灌注损伤

目的 探讨PI3K/Akt信号通路在白藜芦醇减轻大鼠脑缺血再灌注损伤中的作用。方法 将48只成年SD大鼠随机分为假手术组、模型组、白藜芦醇组、LY294002组（Akt抑制剂）,每组12只。利用线栓法制备大鼠脑缺血再灌注损伤模型,造模后24 h进行大鼠神经功能损伤评分和检测脑梗死体积、脑组织髓过氧化物酶（MPO）的活性,免疫印迹法检测脑组织p-Akt、t-Akt的表达水平,ELISA法检测脑组织肿瘤坏死因子-α（TNF-α）的含量。结果 与假手术组相比,模型组大鼠神经功能损伤评分、脑梗死体积、缺血脑组织MPO活性和TNF-α含量均明显增高（P<0.05）,缺血脑组织p-Akt表达水平也明显增高（P<0.05）;与模型组相比,白藜芦醇显著降低大鼠神经功能损伤评分、脑梗死体积、缺血脑组织MPO活性和TNF-α含量（P<0.05）,也显著降低缺血脑组织p-Akt表达水平（P<0.05）;脑室内注射LY294002,显著抑制白藜芦醇的这些作用（P<0.05）。结论 白藜芦醇通过激活PI3K/Akt信号通路减轻大鼠脑缺血再灌注损伤。     

鞘内注射胶质细胞源性神经营养因子对大鼠糖尿病神经病理性疼痛的影响

 目的 探讨胶质细胞源性神经营养因子(glail cell line-derived neurotrophic factor,GDNF)对糖尿病神经病理性疼痛(diabetic neuropathic pain,DNP)大鼠行为学的影响及机制。方法 将雄性SD大鼠50只随机分为对照组(N组,10只)、模型组(40只),造模后的模型组再随机分成DNP组(DC组,10只,仅给予10 μl PBS缓冲液)、GDNF治疗组(DG组,10只,注射2 μg GDNF+10 μl PBS缓冲液)。各组大鼠均测造模前,造模后第3、21天,首次给药或PBS缓冲液后第1、3、7、14天的压尾机械阈值(TFT)与热痛缩爪潜伏期(PWL);处死大鼠后,取L_4-6脊髓组织,采用Western blot法测定脊髓背角磷酸化PI3K、p-AKT、磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)以及磷酸化核糖体S6蛋白激酶(p-S6K)蛋白表达水平。结果 造模后第21 天,与N组比较,模型组的血糖明显升高(P<0.01),且TFT与PWL也均明显缩短(P<0.01);给药后第14 天,与DC组相比较,DG组TFT和PWL均明显升高(P<0.01),且磷酸化PI3K、p-AKT、p-mTOR、p-S6K表达均明显降低(P<0.01);给药后第14天,与N组相比较,DC组TFT和PWL均明显降低(P<0.01),且磷酸化PI3K、p-AKT、p-mTOR、p-S6K表达均明显升高(P<0.01);给药后第14 天,DG组与N组相比较,在TFT、PWL以及磷酸化PI3K、p-AKT、p-mTOR、p-S6K表达等方面的差异均无统计学意义。结论 鞘内注射GDNF能够减轻大鼠DNP,其机制可能与GDNF通过调控PI3K-AKT信号通路,降低p-AKT表达水平,从而抑制p-mTOR和p-S6K的表达有关。