Alteration of surfactant protein A expression in renal cell carcinoma

Surfactant protein-A (SP-A) belongs to a family of collagen-containing C-type lectins called collectins. SP-A is expressed by renal tubule epithelial cells. We investigated the distribution of SP-A in renal cell carcinomas (RCC) using immunohistochemical techniques and western blotting. We used 35 formalin fixed, paraffin embedded (FFPE) RCC tissue samples. We compared results with clinico-pathological parameters of RCC including age, sex, Fuhrman grade, tumor volume, tumor node metastasis (TNM) and clinical stage. SP-A was localized in the glomerulus and renal tubule epithelium in nontumor tissue and strong SP-A immunoreactivity was observed in tumor tissue. SP-A was expressed in the RCC tumor cells (64%) and nontumor cells (34%) in males and RCC tumor cells (90%) and nontumor cells (30%) in females. There was a significant correlation between SP-A immunoreactivity in tumor cells and gender, age, tumor diameter, Fuhrman grade and tumor diameter. Western blot analysis supported the immunohistochemical findings. We present evidence for involvement of SP-A in RCC and suggest that increased SP-A expression in RCC is associated with favorable prognosis.     

Palatability and feeding preferences of Uresiphita maorialis (Lepidoptera: Crambidae) for three Sophora species

In a three-hour bioassay, we tested the palatability and feeding preferences of Uresiphita maorialis (kōwhai moth) for Sophora tetraptera, Sophora microphylla and Sophora prostrata. Palatability tests showed no differences among the Sophora species. Feeding preferences, on the other hand, showed that S. tetraptera and S. microphylla leaves are preferred over S. prostrata leaves. Our results support our field observations in Wellington city parks and gardens showing that S. tetraptera and S. microphylla plants frequently have higher densities of larvae than S. prostrata.     

Mechanical forces regulate elastase activity and binding site availability in lung elastin

Many fundamental cellular and extracellular processes in the body are mediated by enzymes. At the single molecule level, enzyme activity is influenced by mechanical forces. However, the effects of mechanical forces on the kinetics of enzymatic reactions in complex tissues with intact extracellular matrix (ECM) have not been identified. Here we report that physiologically relevant macroscopic mechanical forces modify enzyme activity at the molecular level in the ECM of the lung parenchyma. Porcine pancreatic elastase (PPE), which binds to and digests elastin, was fluorescently conjugated (f-PPE) and fluorescent recovery after photobleach was used to evaluate the binding kinetics of f-PPE in the alveolar walls of normal mouse lungs. Fluorescent recovery after photobleach indicated that the dissociation rate constant (k_off) for f-PPE was significantly larger in stretched than in relaxed alveolar walls with a linear relation between k_off and macroscopic strain. Using a network model of the parenchyma, a linear relation was also found between k_off and microscopic strain on elastin fibers. Further, the binding pattern of f-PPE suggested that binding sites on elastin unfold with strain. The increased overall reaction rate also resulted in stronger structural breakdown at the level of alveolar walls, as well as accelerated decay of stiffness and decreased failure stress of the ECM at the macroscopic scale. These results suggest an important role for the coupling between mechanical forces and enzyme activity in ECM breakdown and remodeling in development, and during diseases such as pulmonary emphysema or vascular aneurysm. Our findings may also have broader implications because in vivo, enzyme activity in nearly all cellular and extracellular processes takes place in the presence of mechanical forces.     

Effect of unilateral and bilateral resistance exercise on maximal voluntary strength,total volume of load lifted,and perceptual and metabolic responses

The present study investigated the effect of unilateral and bilateral resistance exercise (RE) on maximal voluntary strength, total volume of load lifted (TVLL), rating of perceived exertion (RPE) and blood lactate concentration of resistance-trained males. Twelve healthy men were assessed for the leg extension one-repetition maximum (1RM) strength using bilateral and unilateral contractions. Following this assessment, an RE session (3 sets of repetitions to failure) was conducted with bilateral and unilateral (both limbs) contractions using a load of 50% 1RM. The TVLL was calculated by the product of the number of repetitions and the load lifted per repetition. RPE and blood lactate were measured before, during and after each set. Session RPE was measured 30 minutes after RE sessions. There was a significant difference in the bilateral (120.0±11.9) and unilateral (135.0±20.2 kg) 1RM strength (p < 0.05). The TVLL was similar between both RE sessions. Although the repetitions decreased with each successive set, the total number of repetitions completed in the bilateral protocol (48) was superior to the unilateral (40) protocol (p < 0.05). In both bouts, RPE increased with each subsequent set whilst blood lactate increased after set 1 and thereafter remained stable (p < 0.05). The RPE and lactate responses were not significantly different between both sessions. In conclusion, a bilateral deficit in leg extension strength was confirmed, but the TVLL was similar between both RE sessions when exercising to voluntary fatigue. This outcome could be attributed to the number of repetitions completed in the unilateral RE bout. The equal TVLL would also explain the similar perceptual and metabolic responses across each RE session.     

Inhibitory effects of short-term administration of dl-α-lipoic acid on oxidative vulnerability induced by Aβ amyloid fibrils (25–35) in mice

Aβ amyloid peptide is believed to induce oxidative stress leading to inflammation, which is postulated to play a significant role in the toxicity of Alzheimer’s disease (AD). This study was designed to investigate the inhibitory effects of dl-α lipoic acid (LA), a potential free radical scavenger, on oxidative vulnerability induced by intraperitoneal injection of Aβ_25–35 amyloid fibrils in mice. Mice were divided into three groups: control, Aβ amyloid toxicity induced (AT), and LA treated (ATL). Blood Plasma was separated, liver, spleen and brain were dissected and analysis of oxidants, antioxidants, ATPases, glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NFκB) were carried out. Results show biochemical parameters such as reactive oxygen species (ROS) and lipid peroxidation (LPO) were significantly lowered (P < 0.05) and levels of antioxidants and ATPase (P < 0.05) were significantly increased (P < 0.05) in hepatocytes, splenocytes and astrocytes of the ATL group. Moreover, our histological results revealed a decreased GFAP immunoreactivity in the neocortical region and NFκB immunoreactivity in neocortex, liver and spleen. This study reiterates LA as a potent free radical scavenger to combat oxidative vulnerability in the treatment for Aβ amyloid toxicity.     

三氧化二砷对食管癌细胞增殖和热休克蛋白70表达的影响

目的：研究三氧化二砷（As2O3）对食管癌细胞增殖和热休克蛋白70（HSP70）表达的影响。方法：通过相差显微镜、流式细胞术、免疫细胞化学染色和免疫印迹分析等方法观察As2O3对人食管癌细胞株EC1的作用效果和作用机制。结果：与对照组相比,经2μmol/L和5μmol/Las2O3作用的细胞出现明显的生长抑制,G2/M期细胞比例增加;2μmol/Las2O3作用48h后经Ecl细胞HSP70（heat shock protein70）及HSC70(heat shock cognate protein70)表达均增加。结论：As2O3诱导食管癌细胞G2/M期阻滞抑制细胞增殖和生长;HSP70的升高是细胞对As2O3作用后出现的应激反应,并与细胞周期阻滞相关。     

Radioprotective effect of <Emphasis Type="SmallCaps">dl</Emphasis>-α-lipoic acid on mice skin fibroblasts

During the course of cancer radiation treatment, normal skin invariably suffers from the cytotoxic effects of γ-radiation and reactive oxygen species (ROS), which are generated from the interaction between radiation and the water molecules in cells. The present study was designed to investigate the radioprotective role of α-lipoic acid (LA), an antioxidant on murine skin fibroblasts exposed to a single dose of 2, 4, 6, or 8Gy γ-radiation. Irradiation of fibroblasts significantly increased ROS, nitric oxide, and lipid peroxidation (P < 0.001); all of these factors substantially decreased with 100 μM LA treatment. Hydroxyl radical (OH^⋅) production from 8Gy irradiated fibroblasts was measured directly by electron spin resonance using spin-trapping techniques. LA was found to inhibit OH^⋅ production at 100-μM concentrations. Dose-dependent depletion of antioxidants, such as catalase and glutathione reductase, was observed in irradiated fibroblasts (P < 0.001), along with increased superoxide dismutase (P < 0.001). LA treatment restored antioxidant levels. Concentration of the pro-inflammatory cytokine IL-1β was significantly reduced in irradiated fibroblasts when treated with LA. MTT and lactate dehydrogenase assays demonstrated that LA treatment reduced cell injury and protected cells against irradiation-induced cytotoxicity. Thus, we conclude that results are encouraging and need further experiments to demonstrate a possible benefit in cancer patients and the reduction of harmful effects of radiation therapy.     

Synthesis and SAR of novel histamine H3 receptor antagonists

The synthesis and biological evaluation of novel tetrahydroisoquinoline, tetrahydroquinoline, and tetrahydroazepine antagonists of the human and rat H(3) receptors are described. The substitution around these rings as well as the nature of the substituent on nitrogen is explored. Several compounds with high affinity and selectivity for the human and rat H(3) receptors are reported.     

Potent benzimidazolone based human beta(3)-adrenergic receptor agonists

The synthesis and biological evaluation of a series of benzimidazolone beta(3) adrenergic receptor agonists are described. A trend toward the reduction of rat atrial tachycardia upon increasing steric bulk at the 3-position of the benzimidazolone moiety was observed.