Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding

Heterogeneity among Helicobacter pylori strains in gastric epithelial adherence is postulated to contribute to pathogen fitness in the physiologically diverse human population. H. pylori adherence to ABO and Lewis b (Leb) blood group antigens in the human stomach is mediated by the blood group antigen-binding adhesin BabA. Approximately 70% of Swedish and U.S. H. pylori clinical isolates exhibit Leb binding, but here we show that the babA gene is present in each of 10 Leb-nonbinding strains. Fluorescence microscopy identified occasional bacterial cells with a Leb-binding phenotype in populations of Leb-nonbinding strains. Thus, nonbinding seemed to be a metastable phenotype. To model metastable transition into the virulence-associated Leb-binding mode, Leb-binding clones were isolated from nonadherent strains by panning with Leb-magnetic beads and characterized. Strain 17875 has two babA genes, babA1 (silent) and babA2 (expressed). We found that a babA2-cam derivative of strain 17875 regained Leb binding by recombination of the formerly silent babA1 gene into the expressed and partially homologous babB locus. The chimeric BabB/A adhesin binds Leb with an affinity similar to that of wild-type BabA adhesin, but its expression level was lower and was subject to phase variation through slipped-strand mispairing. Equivalent results were obtained with strain NCTC11638. We propose that adhesin metastability and heterogeneity contributes to bacterial fitness and results in some clones having potential for periodic activation and deactivation of virulence appropriate for intensity of the host response to infection.     

Y‐632 inhibits heat shock protein 90 (Hsp90) function by disrupting the interaction between Hsp90 and Hsp70/Hsp90 organizing protein,and exerts antitumor activity in vitro and in vivo

Heat shock protein 90 (Hsp90) stabilizes a variety of proteins required for cancer cell survival and has been identified as a promising drug target for cancer treatment. To date, several Hsp90 inhibitors have entered into clinical trials, but none has been approved for cancer therapy yet. Thus, exploring new Hsp90 inhibitors with novel mechanisms of action is urgent. In the present study, we show that Y‐632, a novel pyrimidine derivative, inhibited Hsp90 in a different way from the conventional Hsp90 inhibitor geldanamycin. Y‐632 induced degradation of diverse Hsp90 client proteins through the ubiquitin–proteasome pathway, as geldanamycin did; however, it neither directly bound to Hsp90 nor inhibited Hsp90 ATPase activity. Y‐632 inhibited Hsp90 function mainly through inducing intracellular thiol oxidation, which led to disruption of the Hsp90–Hsp70/Hsp90 organizing protein complex and further induced cell adhesion inhibition, G₀/G₁ cell cycle arrest, and apoptosis. Moreover, Y‐632 efficiently overcame imatinib resistance mediated by Bcr‐Abl point mutations both in vitro and in vivo. We believe that Y‐632, acting as a novel small‐molecule inhibitor of the Hsp90–Hsp70/Hsp90 organizing protein complex, has great potential to be a promising Hsp90 inhibitor for cancer therapy, such as for imatinib‐resistant leukemia.     

海尔福口服液治疗地方性砷中毒效果观察

目的探讨海尔福口服液对地方性砷中毒患者的治疗效果。方法选择已明确诊断的地方性砷中毒患者35例,按规定剂量服药,分2个疗程,每疗程服药30 d,2疗程间隔2周,每疗程结束取尿测定尿砷（As）和尿羟脯氨酸（Hop）含量,并观察病情变化。结果尿As第1疗程虽有一定程度降低,但不明显,第2疗程尿As明显低于治疗前（P〈0.05）;尿Hop治疗前后比较,两疗程结果均降低,第2疗程比治疗前明显降低（P〈0.05）;患者自觉症状明显改善。结论海尔福口服液可改善地方性砷中毒患者的自觉症状,对患者尿As和尿Hop有一定影响。     

饮水锶对大鼠骨骼生长发育影响的实验研究

研究了高锶饮水对大鼠骨骼生长发育的影响。结果表明，饮水中锶浓度为５～５００ｍｇ／Ｌ达１２周可引起Ｗｉｓｔａｒ大鼠血清、尿、股骨、颌骨和牙齿中锶含量增高，呈明显的剂量－反应关系。同时，锶还可使骨骼钙含量降低，牙齿钙含量和骨骼的骨密度增高，以及除第１２周雌性大鼠外血清钙水平下降。尚未发现锶对动物体重、体长、血清ＡＫＰ活性、尿钙水平以及股骨弯曲断裂载荷的影响。然而，锶对动物骨骼生长发育影响性别之间存在差异，如在第１２周染锶组雄性大鼠血清钙含量降低，而雌性大鼠升高；在第４周和第８周时，仅雄性大鼠尿Ｈｏｐ／Ｃｒ比值增高，而雌性大鼠维持于正常水平；Ｓｒ２＋还使雄性大鼠颌骨骨密度增加，而雌性大鼠股骨骨密度增加。上述改变提示可能是动物性别之间在内分泌调节和代谢过程上不同的结果。     

Extraction of the hormonal substance from hop

Substances that suppressed a gain in the weight of pregnant mare's serum gonadotropin (PMSG)-primed immature rat ovaries, were obtained from dried powder of the hop cone. The substances were designated F_1a-I and F_1a-II. In immature rats at 4 days after PMSG priming, ovarian weights decreased by 58.0 ± 3.7 and 66.9 ± 6.6% the control by injections with 4 mg each of F_1a-I and F_1a-II, respectively. Apparent M^rs of the partially purified fractions were nearly 80 000 (F_1a-I) and 66 000–80 000 (F_1a-II). They were water-soluble. Acidic and neutral sugars were detected in the hydrolysate of the substance.     

Kinematic and electromyographic analysis in patients with patellofemoral pain syndrome during single leg triple hop test

Possible delays in pre-activation or deficiencies in the activity of the dynamic muscle stabilizers of the knee and hip joints are the most common causes of the patellofemoral pain syndrome (PFPS). The aim of the study was to compare kinematic variables and electromyographic activity of the vastus lateralis, biceps femoris, gluteus maximus and gluteus medius muscles between patients with PFPS and health subjects during the single leg triple hop test (SLTHT). This study included 14 female with PFPS (PFPS group) and 14 female healthy with no history of knee pain (Healthy group). Kinematic and EMG data ware collected through participants performed a single session of the SLTHT. The PFPS group exhibited a significant increase (p < 0.05) in the EMG activity of the biceps femoris and vastus lateralis muscles, when compared with the healthy group in pre-activity and during the stance phase. This same result was also found for the vastus lateralis muscle (p < 0.05) when analyzing the EMG activity during the eccentric phase of the stance phase. In kinematic analysis, no significant differences were found between the groups. These results indicate that biceps femoris and vastus lateralis muscles mainly during the pre-activation phase and stance phases of the SLTHT are more active in PFPS group among healthy group.     

Knockdown of Hop downregulates RhoC expression,and decreases pseudopodia formation and migration in cancer cell lines

The Hsp90/Hsp70 organising protein (Hop) is a co-chaperone that mediates the interaction of Hsp90 and Hsp70 molecular chaperones during assembly of Hsp90 complexes in cells. Formation of Hsp90 complexes is a key intermediate step in the maturation and homeostasis of oncoproteins and several hormone receptors. In this paper, we demonstrate that knockdown of Hop decreased migration of Hs578T and MDA-MB-231 breast cancer cells. Hop was identified in isolated pseudopodia fractions; it colocalised with actin in lamellipodia, and co-sedimented with purified actin in vitro. Knockdown of Hop caused a decrease in the level of RhoC GTPase, and significantly inhibited pseudopodia formation in Hs578T cells. Our data suggest that Hop regulates directional cell migration by multiple unknown mechanisms.     

Hop Extract Produces Antinociception by Acting on Opioid System in Mice

In the present study, the antinociceptive profiles of hop extract were characterized in ICR mice. Hop extract administered orally (from 25 to 100 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Antinociceptive action of hop extract was maintained at least for 60 min. Moreover, cumulative response time of nociceptive behaviors induced with intraplantar formalin injection was reduced by hop extract treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P (0.7 µg) or glutamate (20 µg) was diminished by hop extract. Intraperitoneal pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by hop extract in the writhing test. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an α₂-adrenergic receptor antagonist) did not affect antinociception induced by hop extract in the writhing test. Our results suggest that hop extract shows an antinociceptive property in various pain models. Furthermore, the antinociceptive effect of hop extract may be mediated by opioidergic receptors, but not serotonergic and α₂-adrenergic receptors.     

Knee kinematics and kinetics during gait, step and hop in males with a 16 years old ACL injury compared with matched controls

The objective of this study was to compare subjects who sustained an ACL injury during soccer 16 years ago with a control group with regard to knee kinematics and kinetics of gait, step activity and cross over hop. Secondly, in the injured subjects, the purpose was to study the impact on kinematics and kinetics of characteristics such as operative status, meniscal resection, being symptomatic, having knee extensor weakness and of having radiographic knee OA. Data from a 3-dimensional gait analysis system (VICON) were used to calculate kinetics and kinematics during gait, step activity and cross over hop of 12 male subjects who had an anterior cruciate ligament injury 16 years earlier. Twelve uninjured subjects matched for age, sex, BMI and activity level served as controls. No significant differences in knee kinematics and kinetics between the ACL group and the control group were found. The variability of some parameters of step and all parameters of hop activity was generally larger in the ACL injured subjects compared with the controls. The ACL injured subjects had a significantly worse clinical status compared with the controls. Reduced knee extension strength was associated with joint moment reductions especially during step activity and cross over hop. Despite a significantly worse clinical status, as determined by self-report and isokinetic strength testing, no significant differences were seen in knee joint kinetics and kinematics in an ACL injured group 16 years after injury compared with a matched control group. The variation was larger among the ACL injured subjects indicating the need for larger study groups in gait and movement analysis in long-term follow-up of ACL injury.