BACKGROUND & AIMS: PURPOSE:The most common genitourinary malignancy in China is bladder transitional cell carcinoma (TCC). Early diagnosis of new and recurrent bladder cancers, followed by timely treatment, will help decrease mortality. There are currently no satisfactory markers for bladder cancer available in clinics. Better diagnostic methods are highly demanded. EXPERIMENTAL DESIGN:In this research, we have used comprehensive expressed sequence tag analysis, serial analysis of gene expression, and microarray analysis and quickly discovered a candidate marker, urothelial carcinoma associated 1 (UCA1). The UCA1 gene was characterized and its performance as a urine marker was analyzed by reverse transcription-PCR with urine sediments. A total of 212 individuals were included in this study, 94 having bladder cancers, 33 ureter/pelvic cancers, and 85 normal and other urinary tract disease controls. RESULTS:UCA1 was identified as a novel noncoding RNA gene dramatically up-regulated in TCC and it is the most TCC-specific gene yet identified. The full-length cDNA was 1,439 bp, and sequence analysis showed that it belonged to the human endogenous retrovirus H family. Clinical tests showed that UCA1 assay was highly specific (91.8%, 78 of 85) and very sensitive (80.9%, 76 of 94) in the diagnosis of bladder cancer and was especially valuable for superficial G2-G3 patients (sensitivity 91.1%, 41 of 45). It showed excellent differential diagnostic performance in various urinary tract diseases without TCC. CONCLUSIONS:UCA1 is a very sensitive and specific unique marker for bladder cancer. It could have important implications in postoperative noninvasive follow-up. This research also highlights a shortcut to new cancer diagnostic assays through integration of in silico isolation methods with translational clinical tests based on RNA detection protocols.

背景与目标：

BACKGROUND & AIMS: The fluorescence intensity decay of the single tryptophan residue, Trp-187, of free annexin V is described by the sum of three lifetime components (5.4, 1.3, and 0.4 ns), which may be correlated to three ground-state classes of Trp conformers. The two major classes (44 and 48%) are embedded in the protein matrix. When annexin V binds to calcium and liposomes made of dioleoylphosphatidylcholine and dioleoylphosphatidylserine, similar results are obtained whatever the (10-200) lipid ratio. The Trp fluorescence decay is fitted with only two components (6.9-7.2 and 2.0-2.2 ns). Decay-associated spectra reveal that the longest lifetime of bound annexin V can be related to Trp residues (60%) located in a partially polar environment, which could correspond to the protein-membrane interface. The shortest lifetime is attributed to Trp residues (40%) which reside in a hydrophobic surroundingthese Trp residues would penetrate into the phospholipid membrane and contribute to the stabilization of the 2D-array of annexin V molecules.

背景与目标： Trp-187，游离膜联蛋白V的单个色氨酸残基的荧光强度衰减由三个寿命分量 (5.4、1.3和0.4 ns) 的总和描述，这可能与Trp构象的三个基态类别相关。两个主要类别 (44和48%) 嵌入蛋白质基质中。当膜联蛋白V与钙和由二油酰基磷脂酰胆碱和二油酰基磷脂酰丝氨酸制成的脂质体结合时，无论 (10-200) 脂质比率如何，都获得相似的结果。Trp荧光衰减仅适合两种组分 (6.9-7.2和2.0-2.2 ns)。衰变相关光谱表明，结合膜联蛋白V的最长寿命可能与位于部分极性环境中的Trp残基 (60%) 有关，这可能对应于蛋白质-膜界面。最短的寿命归因于存在于疏水性周围的Trp残基 (40%)，这些Trp残基会渗透到磷脂膜中，并有助于膜联蛋白V分子的2d阵列的稳定。

BACKGROUND & AIMS: :We investigated the ability of systolic and diastolic carotid artery longitudinal wall motion (CALM) to delineate expected differences in arterial health in individuals representing a range of both age and health status. We recruited 161 younger healthy adults (aged 24 ± 5 y), 51 older healthy adults (aged 70 ± 5 y) and 14 adults with coronary artery disease (aged 67 ± 8 y) for resting assessment of CALM and arterial stiffness. All CALM parameters were reduced in the old healthy adults and adults with coronary artery disease compared with the young healthy adults (p < 0.01), with diastolic velocity and maximum diastolic acceleration being further reduced in the adults with coronary artery disease than in the older healthy adults (p < 0.01). Diastolic CALM parameters were more strongly related to age (β range: -0.46 to -0.53) than systolic CALM parameters (β range: -0.24 to -0.44). In contrast to previous examinations of a variety of CALM parameters, diastolic CALM may provide superior promise in terms of characterizing arterial wall properties, with additional sensitivity to cardiovascular disease status.

背景与目标： : 我们研究了收缩期和舒张期颈动脉纵向壁运动 (CALM) 描绘代表年龄和健康状况范围的个体的动脉健康预期差异的能力。我们招募了161名年轻的健康成年人 (24 ± 5岁)，51名老年健康成年人 (70 ± 5岁) 和14名患有冠状动脉疾病的成年人 (67 ± 8岁) 进行静息评估平静和动脉僵硬度。与年轻健康成年人相比，老年健康成年人和患有冠状动脉疾病的成年人的所有CALM参数均降低 (p <0.01)，与老年健康成年人相比，患有冠状动脉疾病的成年人的舒张速度和最大舒张加速度进一步降低 (p <0.01)。舒张期平静参数与年龄 (β 范围: -0.46至-0.53) 的相关性高于收缩期平静参数 (β 范围: -0.24至-0.44)。与以前对各种平静参数的检查相比，舒张期平静在表征动脉壁特性方面可能具有出色的前景，并且对心血管疾病状态具有额外的敏感性。

BACKGROUND & AIMS: :In order to understand the effect of pH on the formation of electrostatic complexes between lysozyme and low methoxyl (LM) pectin, mixtures were prepared at a fixed lysozyme concentration (0.714g.L-1) by progressive addition of LM pectin (from 0 to 4g.L-1). Turbidity analysis allowed to determine specific conditions of pH and lysozyme/LM pectin ratio for optimal complex aggregation. The intrinsic fluorescence enhancement observed upon binding of LM pectin to lysozyme was correlated with the formation of intermolecular aggregates. Conversely, the intrinsic fluorescence decrease observed at higher LM pectin amounts was correlated with the dissociation of intermolecular aggregates. UV absorption spectroscopy showed modifications in lysozyme conformation during both the aggregation phase and the dissociation phase. The role of electrostatic interactions in the formation of lysozyme/LM pectin complexes is discussed in relation to the overall structure and the charge density profile of the two biopolymers.

背景与目标： 为了了解pH对溶菌酶和低甲氧基 (LM) 果胶之间静电复合物形成的影响，通过逐渐加入LM果胶 (0至4g.L-1)，在固定的溶菌酶浓度 (0.714g.L-1) 下制备混合物。浊度分析可以确定pH和溶菌酶/LM果胶比率的特定条件，以实现最佳的复合聚集。LM果胶与溶菌酶结合后观察到的固有荧光增强与分子间聚集体的形成有关。相反，在较高的LM果胶量下观察到的固有荧光降低与分子间聚集体的解离有关。紫外吸收光谱显示，在聚集相和解离相中，溶菌酶构象都发生了变化。讨论了静电相互作用在溶菌酶/LM果胶复合物形成中的作用，涉及两种生物聚合物的整体结构和电荷密度分布。

BACKGROUND & AIMS: :Cell-attached patch-clamp recordings on native striated myofibers from adult dystrophic mdx mice revealed a higher occurrence and open probability compared to non-dystrophic wild-type myofibers of a 30 pS voltage-insensitive Ca2+-permeable channel, inhibited by Gd3+, streptomycin and ruthenium red. Myofibers from in vivo exercised animals had higher channel occurrence and/or open probability. Insulin-like growth factor 1 (3.3 nM) induced and/or enhanced channel activity, via PI3 kinase, in wild-type but not in mdx myofibers. Interestingly, in both genotypes the current was silenced by db-cAMP or pentoxifylline, a phosphodiesterase inhibitor. The channel activity/occurrence in pentoxifylline-treated exercised mdx (50 mg/kg/day i.p. for 4-8 weeks) overlapped that of exercised wild-type mice. Thus, a growth factor-sensitive current, likely due to a TRP channel, is activated in vivo by exercise in native striated fibers; its deregulation in the absence of dystrophin may contribute to Ca2+ homeostasis alteration. The possibility to pharmacologically counteract abnormal channel activity discloses important therapeutic application.

背景与目标： : 成年营养不良mdx小鼠的天然横纹肌纤维上的细胞附着膜片钳记录显示，与30 ps电压不敏感的Ca2渗透通道的非营养不良野生型肌纤维相比，其发生的可能性和开放的可能性更高，受到Gd3，链霉素和钌的抑制红。来自体内运动动物的肌纤维具有更高的通道发生和/或开放概率。胰岛素样生长因子1 (3.3纳米) 通过PI3激酶在野生型但在mdx肌纤维中诱导和/或增强通道活性。有趣的是，在两种基因型中，电流均被磷酸二酯酶抑制剂db-cAMP或己酮可可碱沉默。己酮可可碱处理的运动mdx (50 mg/kg/天，每天腹腔注射4-8周) 的通道活性/发生与运动野生型小鼠的通道活性/发生重叠。因此，可能是由于TRP通道引起的对生长因子敏感的电流在体内通过在天然横纹纤维中的运动而被激活; 在没有肌营养不良蛋白的情况下，其失调可能会导致Ca2稳态改变。从药理学上消除异常通道活性的可能性揭示了重要的治疗应用。

BACKGROUND & AIMS: :Studies of transcriptome profiles have provided new insights into mechanisms underlying the development of hypertension. Cell type heterogeneity in tissue samples, however, has been a significant hindrance in these studies. We performed a transcriptome analysis in medullary thick ascending limbs of the loop of Henle isolated from Dahl salt-sensitive rats. Genes differentially expressed between Dahl salt-sensitive rats and salt-insensitive consomic SS.13(BN) rats on either 0.4% or 7 days of 8.0% NaCl diet (n=4) were highly enriched for genes located on chromosome 13, the chromosome substituted in the SS.13(BN) rat. A pathway involving cell proliferation and cell cycle regulation was identified as one of the most highly ranked pathways based on differentially expressed genes and by a Bayesian model analysis. Immunofluorescent analysis indicated that just 1 week of a high-salt diet resulted in a severalfold increase in proliferative medullary thick ascending limb cells in both rat strains, and that Dahl salt-sensitive rats exhibited a significantly greater proportion of medullary thick ascending limb cells in a proliferative state than in SS.13(BN) rats (15.0±1.4% versus 10.1±0.6%; n=7-9; P<0.05). The total number of cells per medullary thick ascending limb section analyzed was not different between the 2 strains. The study revealed alterations in regulatory pathways in Dahl salt-sensitive rats in tissues highly enriched for a single cell type, leading to the unexpected finding of a greater increase in the number of proliferative medullary thick ascending limb cells in Dahl salt-sensitive rats on a high-salt diet.

背景与目标： : 转录组谱的研究为高血压发展的机制提供了新的见解。然而，在这些研究中，组织样本中的细胞类型异质性一直是一个重大障碍。我们对从达尔盐敏感大鼠中分离出的Henle环的髓质厚上升肢进行了转录组分析。在0.4% 或7天的8.0% NaCl饮食 (n = 4) 的Dahl盐敏感大鼠和盐不敏感的康体SS.13(BN) 大鼠之间差异表达的基因高度富集位于13号染色体上的基因，该染色体在SS.13(BN) 大鼠中被取代。基于差异表达基因和贝叶斯模型分析，涉及细胞增殖和细胞周期调控的途径被确定为排名最高的途径之一。免疫荧光分析表明，仅1周的高盐饮食就导致两种大鼠品系中增殖的髓质厚上升肢体细胞增加了几倍，并且Dahl盐敏感大鼠在增殖状态下表现出比SS.13(BN) 大鼠明显更大的髓质厚上升肢体细胞比例 (15.0 ± 1.4% 对10.1 ± 0.6%; n = 7-9; P<0.05)。分析的每个髓质厚上升肢切片的细胞总数在2个菌株之间没有差异。该研究揭示了Dahl盐敏感大鼠在单细胞类型高度富集的组织中调节途径的改变，导致意外发现Dahl盐敏感大鼠中增殖性髓质厚上升肢体细胞的数量增加高盐饮食。

BACKGROUND & AIMS: A study of three fluorescent anthroyl probes has been carried out using pure and mixed monomolecular films with dipalmitoylphosphatidylcholine. In addition, fluorescence depolarization and differential scanning calorimetry data were obtained from dipalmitoylphosphatidylcholine vesicles with incorporated anthroyl probes. The three probes used were 2-(9-anthroyl)palmitic acid. 12-(9-anthroyl)stearic acid, and 16-(9-anthroyl)palmitic acid. The latter probe was synthesized for these studies. In monolayers the probes shifted the onset of the liquid-condensed/liquid-expanded monolayer phase transition with the extent of the shift decreasing in the order2-(9-anthroyl)palmitic acid greater than 12-(9-anthroyl)stearic acid greater than 16-(9-anthroyl)stearic acid. A corresponding decrease in the gel-liquid crystalline bilayer transition temperature (Tc) showed the same order of perturbation in both the fluorescence depolarization and differential scanning calorimetry data. Locating the anthroyl entity in the center of the bilayer would appear to provide a minimum perturbation.

背景与目标： 已使用纯的和混合的单分子膜与二棕榈酰磷脂酰胆碱进行了对三种荧光拟人基探针的研究。此外，荧光去极化和差示扫描量热法数据是从结合了人角基探针的二棕榈酰磷脂酰胆碱囊泡获得的。使用的三种探针是2-(9-甘草酸) 棕榈酸。12-(9-甘草酸) 硬脂酸，和16-(9-人甘草酸) 棕榈酸。后一种探针是为这些研究合成的。在单层中，探针改变了液体冷凝/液体膨胀单层相变的开始，而这种转变的程度以2-(9-人甘草酸) 大于12-(9-人甘草酸) 的顺序减小硬脂酸大于16-(9-拟人酰) 硬脂酸。凝胶-液晶双分子层转变温度 (Tc) 的相应降低在荧光去极化和差示扫描量热法数据中显示出相同的扰动顺序。将拟人酰实体定位在双分子层的中心似乎提供了最小的摄动。

BACKGROUND & AIMS: :Purinergic stimulation of human airway epithelia results in a prolonged increase in ciliary beat frequency that depends on calcium-mediated cAMP production [Lieb, T., Wijkstrom Frei, C., Frohock, J.I., Bookman, R.J. and Salathe, M. (2002) Prolonged increase in ciliary beat frequency after short-term purinergic stimulation in human airway epithelial cells. J. Physiol. (Lond.) 538, 633-646]. Here, fully differentiated human airway epithelial cells in culture are shown to express calcium-stimulated transmembrane adenylyl cyclase (tmAC) isoforms (types 1, 3, and 8) by reverse transcription polymerase chain reaction. Immunohistochemistry of tracheal sections and fully differentiated airway epithelial cell cultures revealed polarized expression of these tmACs, with types 1 and 8 localized to the apical membrane and thus at the position required for ciliary regulation. Real-time, ciliated-cell specific cAMP production by tmACs upon apical, purinergic stimulation with UTP was confirmed using fluorescent energy resonance transfer between fluorescently tagged PKA subunits.

背景与目标： : 嘌呤能刺激人气道上皮细胞导致睫状搏动频率的延长增加，这取决于钙介导的cAMP产生 [Lieb，T.，Wijkstrom Frei，C.，Frohock，J.I.，Bookman，r.j.和salate，M. (2002) 人气道上皮细胞短期嘌呤能刺激后睫状搏动频率的延长增加。J. Physiol。(Lond。) 538，633-646]。在这里，通过逆转录聚合酶链反应显示培养物中完全分化的人气道上皮细胞表达钙刺激的跨膜腺苷酸环化酶 (tmAC) 亚型 (1、3和8型)。气管切片和完全分化的气道上皮细胞培养物的免疫组织化学显示这些tmac的极化表达，其中1型和8型位于根尖膜上，因此位于纤毛调节所需的位置。使用荧光标记的PKA亚基之间的荧光能量共振转移，证实了tmACs在UTP的顶端，嘌呤能刺激下实时，纤毛细胞特异性cAMP的产生。

BACKGROUND & AIMS: :The level of cyclic AMP in various fractions of rat skeletal tissue was measured after in vitro or in vivo administration of parathyroid hormone and calcitonin. Incubations of bone fractions prepared from young (5 weeks of age thyroparathyroidectomized rats revealed that both parathyroid hormone and calcitonin increased the cyclic AMP level in fractions of epiphysis, metaphysis and marrow cells. Cyclic AMP accumulation in incubated perisoteum and diaphysis were induced solely by parathyroid hormone. In in vivo experiments the cyclic AMP level in the tibia of the thyroparathyroidectomized rat was increased by infusion of either parathyroid hormone or calcitonin, and the simultaneous administration of each maximally effective dose of the two hormones exhibited an additive effect. Within 2 min, parathyroid hormone infusion caused an elevation of cyclic AMP content in periosteum and metaphysis. Rapid increase of cyclic AMP in the metaphysis was also induced by calcitonin, and the effect of the two hormones on cyclic AMP accumulation in this fraction was additive. Small but significant increase of cyclic AMP in the diaphysis was detected at 5 min after the administration of parathyroid hormone. Calcitonin infusion did not show any consistent effects on periosteum and diaphysis.

背景与目标： : 在体外或体内给予甲状旁腺激素和降钙素后，测量大鼠骨骼组织各部分中的环AMP水平。从年轻的 (5周龄甲状腺旁腺切除的大鼠) 制备的骨组分的孵育表明，甲状旁腺激素和降钙素均增加了骨骺组分中的环AMP水平，干phy端和骨髓细胞。仅由甲状旁腺激素诱导孵育的perisoteum和daphysis中的循环AMP积累。在体内实验中，甲状旁腺激素或降钙素的输注增加了甲状旁腺切除大鼠胫骨中的循环AMP水平，两种激素的最大有效剂量的同时给药均表现出累加作用。在2分钟内，甲状旁腺激素输注导致骨膜和干骺端循环AMP含量升高。降钙素也诱导了干骺端循环AMP的快速增加，两种激素对该级分中环AMP积累的影响是累加的。甲状旁腺激素给药后5分钟，检测到骨干中环AMP的少量但显着增加。降钙素输注对骨膜和骨干没有显示出任何一致的作用。

BACKGROUND & AIMS: :We reported previously that onset of oligodendrocyte precursor cell (OPC) differentiation is accompanied by an increase in intracellular pH (pH(i)). We show that OPC differentiation is dependent primarily on a permissive pH(i) value. The highest differentiation levels were observed for pH(i) values around 7.15 and inhibition of differentiation was observed at slightly more acidic or alkaline values. Clamping the pH(i) of OPCs at 7.15 caused a transient activation of ERK1/2 that was not observed at more acidic or alkaline values. Furthermore, inhibition of ERK activation with the UO126 compound totally prevented OPC differentiation in response to pH(i) shift. These results indicate that pH(i), acting through the ERK1/2 pathway, is a key determinant for oligodendrocyte differentiation. We also show that this pH(i) pathway is involved in the process of retinoic acid-induced OPC differentiation.

背景与目标： : 我们以前曾报道过少突胶质细胞前体细胞 (OPC) 分化的开始伴随着细胞内pH(i)) 的增加。我们表明OPC的分化主要取决于允许的pH(i) 值。对于7.15附近的pH(i) 值观察到最高的分化水平，并且在稍微更酸性或碱性值观察到分化的抑制。将OPCs的pH(i) 夹在7.15引起ERK1/2的瞬时活化，这在更酸性或碱性值下没有观察到。此外，用UO126化合物抑制ERK活化完全阻止了响应pH(i) 位移的OPC分化。这些结果表明，pH(i) 通过ERK1/2途径起作用，是少突胶质细胞分化的关键决定因素。我们还表明，该pH(i) 途径参与了视黄酸诱导的OPC分化过程。

BACKGROUND & AIMS: INTRODUCTION:The antiplatelet effects of low-dose aspirin (LDA) vary between individuals. Here, we investigated the relationship between the incidence of LDA-induced mucosal injury, antiplatelet effects of LDA, and intragastric pH. METHODS:We evaluated gastric injury severity and platelet function using the VerifyNow® System before and after administration of 100 mg aspirin for 7 days to 18 young healthy subjects (study 1). We investigated whether injury was correlated with platelet function and gastric juice pH in 45 patients with cardiovascular disease administered LDA daily (study 2). RESULTS:In study 1, platelet aggregation was attenuated by LDA to different degrees. Although 55.6% of subjects (10/18) developed gastric injury of modified Lanza score (MLS) ≥ 3, no significant difference in platelet function was detected between the mild (n = 8, MLS: 0-2) and severe injury groups (n = 10, MLS: 3-5). In study 2, the severity of LDA-induced injury was associated with gastric juice pH, but not with antiplatelet effects of LDA. DISCUSSION:In contrast to gastric juice pH, the antiplatelet effect had no correlation with the severity of gastric mucosal injury. Monitoring gastric acidity, rather than platelet function, may be useful for predicting the risk of gastric injury during LDA treatment.

背景与目标：

BACKGROUND & AIMS: :Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino) cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation. The therapeutic potential of PHCCC, however, is hindered by dose-limiting toxicity, poor solubility, and the need for frequent dosing. We hypothesized liposomal delivery of PHCCC might enable safe, effective delivery of this hydrophobic drug to exploit metabolism as a means of controlling inflammation in self-reactive immune cells. PHCCC was readily encapsulated in liposomes modified with polyethylene glycol. Under sink conditions, controlled release resulted in 58% of drug released into media over 18 hours. Culture of primary DCs with PHCCC liposomes reduced pro-inflammatory cytokine secretion while reducing toxicity four-fold compared with soluble PHCCC. During co-culture of DCs with myelin-reactive T cells from transgenic mice, PHCCC liposomes reduced T cell proliferation and interferon gamma secretion. These results support the potential of using liposomes to promote tolerance through biocompatible delivery of metabolic modulators. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2977-2985, 2017.

背景与目标： 多发性硬化症 (MS) 是一种自身免疫性疾病，其中髓磷脂被错误地识别为外来物质并受到适应性免疫系统的攻击。树突状细胞 (dc) 通过向T细胞呈递抗原来指导适应性免疫，因此可作为自身免疫疗法的靶标。N-Phenyl-7-(羟基亚氨基) 环丙 [b]chromen-1a-carboxamide (PHCCC) 是代谢型谷氨酸受体4 (mGluR4) 的正变构调节剂，可以通过改变细胞因子分泌来促进调节性T细胞分化。然而，PHCCC的治疗潜力受到剂量限制毒性，溶解度差以及需要频繁给药的阻碍。我们假设PHCCC的脂质体递送可能使这种疏水药物的安全，有效的递送能够利用代谢作为控制自我反应免疫细胞中炎症的手段。PHCCC很容易封装在用聚乙二醇修饰的脂质体中。在下沉条件下，受控释放导致药物在18小时内释放到培养基中的58%。与可溶性PHCCC相比，用PHCCC脂质体培养原代dc可减少促炎性细胞因子的分泌，同时降低毒性的四倍。在dc与转基因小鼠的髓磷脂反应性T细胞共培养期间，PHCCC脂质体降低了T细胞的增殖和干扰素 γ 的分泌。这些结果支持了使用脂质体通过代谢调节剂的生物相容性递送来促进耐受性的潜力。©2017威利期刊公司J生物材料Res部分A: 105A: 2977-2985，2017。

BACKGROUND & AIMS: :Inappropriate activation of the intrarenal renin-angiotensin system induces generation of reactive oxygen species and tubulointerstitial inflammation, which contribute to salt-sensitive hypertension (SSHT). Liver-type fatty acid-binding protein is expressed in proximal tubules in humans, but not in rodents, and may play an endogenous antioxidative role. The objective of the present study was to examine the antioxidative effect of liver-type fatty acid-binding protein on post-angiotensin II SSHT model in transgenic mice with selective overexpression of human liver-type fatty acid-binding protein in the proximal tubules. The transgenic mice showed marked protection against angiotensin II-induced SSHT. Overexpression of tubular liver-type fatty acid-binding protein prevented intrarenal T-cell infiltration and also reduced reactive oxygen species generation, intrarenal renin-angiotensin system activation, and monocyte chemotactic protein-1 expression. We also performed an in vitro study using the murine proximal tubular cell lines with or without recombinant liver-type fatty acid-binding protein and murine proximal tubular cell lines transfected with human liver-type fatty acid-binding protein, and found that gene transfection of liver-type fatty acid-binding protein and, in part, recombinant liver-type fatty acid-binding protein administration had significantly attenuated angiotensin II-induced reactive oxygen species generation and the expression of angiotensinogen and monocyte chemotactic protein-1 in murine proximal tubular cell lines. These findings indicated that liver-type fatty acid-binding protein in the proximal tubules may protect against angiotensin II-induced SSHT by attenuating activation of the intrarenal renin-angiotensin system and reducing oxidative stress and tubulointerstitial inflammation. Present data suggest that liver-type fatty acid-binding protein in the proximal tubules may be a novel therapeutic target for SSHT.

背景与目标： : 肾内肾素-血管紧张素系统的不适当激活会导致活性氧和肾小管间质炎症的产生，从而导致盐敏感性高血压 (SSHT)。肝型脂肪酸结合蛋白在人类近端小管中表达，但在啮齿动物中不表达，并且可能发挥内源性抗氧化作用。本研究的目的是研究肝型脂肪酸结合蛋白对血管紧张素II后SSHT模型的抗氧化作用，该模型在近端小管中选择性过表达人肝型脂肪酸结合蛋白。转基因小鼠对血管紧张素II诱导的SSHT具有明显的保护作用。肾小管型脂肪酸结合蛋白的过表达阻止了肾内T细胞的浸润，并减少了活性氧的产生，肾内肾素-血管紧张素系统的激活和单核细胞趋化蛋白-1的表达。我们还使用带有或不带有重组肝型脂肪酸结合蛋白的鼠近端肾小管细胞系和转染人肝型脂肪酸结合蛋白的鼠近端肾小管细胞系进行了体外研究，发现基因转染肝型脂肪酸结合蛋白，在某种程度上，重组肝型脂肪酸结合蛋白的施用显着减弱了血管紧张素II诱导的活性氧的产生以及鼠近端肾小管细胞系中血管紧张素原和单核细胞趋化蛋白-1的表达。这些发现表明，近端肾小管中的肝型脂肪酸结合蛋白可以通过减弱肾内肾素-血管紧张素系统的激活并减少氧化应激和肾小管间质炎症来预防血管紧张素II诱导的SSHT。目前的数据表明，近端小管中的肝型脂肪酸结合蛋白可能是SSHT的新治疗靶标。

BACKGROUND & AIMS: :We have established that 2,3-diphosphoglycerate (2,3-DPG) content and intracellular pH exert separate, but interdependent, effects on the equilibrium solubility (csat) of deoxyhemoglobin S (deoxy-Hb S) that act in concert to modulate intraerythrocytic polymer formation. In a nonphysiologic csat assay system, a steep dependence of csat on pH in the physiologic range 7.0 to 7.6 was shown for both stripped (Hb) and DPG-saturated deoxy-Hb S (Hb-DPG). The solubility-pH profile for Hb under near-physiologic buffer conditions also showed that csat increased steeply in the same pH range (6.8 to 7.6). The effect of 2,3-DPG on csat under near-physiologic conditions was evaluated separately. At pH 7.20, the pH of the human red blood cell, csat values for Hb and Hb-DPG were 19.56 +/- 0.14 and 17.95 +/- 0.45 g/dL, respectively, indicating that the solubility of Hb-DPG is lower than that of Hb by 8.2% +/- 2.3%. Thus, binding of 2,3-DPG in the beta-cleft promotes the polymerization of deoxy-Hb S, the ultimate determinant of cell sickling. Furthermore, because of the abnormal Bohr effect of sickle blood (approximately double that of normal blood), the intracellular pH of deoxygenated sickle erythrocytes should be approximately 0.28 pH unit higher than that of oxygenated cells (ie, 7.41 v 7.13). At the higher pH, the corresponding csat for Hb-DPG is 20.22 g/dL, which is the best estimate of the intrinsic solubility of T-state Hb S under conditions that approximate closely those of pH, temperature, ionic strength, and 2,3-DPG saturation in the fully desaturated sickle erythrocyte.

背景与目标： : 我们已经确定，2,3-二磷酸甘油酸 (2,3-dpg) 含量和细胞内pH对脱氧血红蛋白S (脱氧-Hb S) 的平衡溶解度 (csat) 产生独立但相互依存的影响，而脱氧血红蛋白S (脱氧-Hb S) 协同作用调节红细胞内聚合物的形成。在非生理性csat测定系统中，对于汽提 (Hb) 和DPG饱和脱氧-Hb S (hb-dpg)，显示出csat对7.0至7.6的生理范围内的pH的急剧依赖性。Hb在近生理缓冲条件下的溶解度-pH曲线也表明，在相同的pH范围内 (6.8至7.6)，csat急剧增加。分别评估了近生理条件下2,3-dpg对csat的影响。在pH 7.20时，人红细胞的pH、Hb和hb-dpg的csat值分别为19.56 +/- 0.14和17.95 +/- 0.45g/dL，表明hb-dpg的溶解度比Hb的溶解度低8.2% +/- 2.3%。因此，在 β-裂隙中结合2,3-dpg会促进脱氧-Hb S的聚合，脱氧-Hb S是细胞镰状的最终决定因素。此外，由于镰状血液的异常玻尔效应 (大约是正常血液的两倍)，脱氧镰状红细胞的细胞内pH应该比氧合细胞的pH高约0.28 pH单位 (即7.41 v 7.13)。在较高的pH下，hb-dpg的相应csat为20.22g/dL，这是在非常接近pH、温度、离子强度和完全去饱和镰刀红细胞中2,3-DPG饱和度的条件下，T-态Hb S固有溶解度的最佳估计值。

BACKGROUND & AIMS: :pH 5.9 is optimal for tobacco pollen tube growth in suspension culture. Little pH changes of sugar-mineral medium result from the release of surface-linked compounds from pollen grains. Germination and pollen tube growth bring about a progressive medium acidification resulting in total growth inhibition. An increase of the buffering capacity of the culture medium enhances pollen tube growth. When the pH was kept near the optimum by 25 mM MES-KOH buffer, pollen tubes grew for 4 days and in the presence of casein hydrolysate they reached a length of up to about 4 cm. The growth related acidification of the medium is independent of the presence of mineral cations and is not due to the hydration of respiratory CO(2). It is suggested that it is brought about by proton secretion from pollen tubes.

背景与目标： : pH 5.9对于悬浮培养中的烟草花粉管生长是最佳的。糖矿物培养基的ph值变化很小，这是由于花粉粒中表面连接的化合物的释放所致。发芽和花粉管生长会导致培养基酸化，从而导致总生长抑制。培养基缓冲能力的增加可增强花粉管的生长。当通过25mmmes-KOH缓冲液将pH保持在最佳值附近时，花粉管生长4天，并且在酪蛋白水解产物存在下，它们达到高达约4厘米的长度。与生长相关的培养基酸化与矿物阳离子的存在无关，而不是由于呼吸CO(2) 的水合作用。建议它是由花粉管的质子分泌引起的。