Modulation of hepatic level of microsomal testosterone 7 alpha-hydroxylase, P-450a (P450IIA), by thyroid hormone and growth hormone in rat liver

The effects of thyroid hormone and growth hormone on microsomal testosterone 7 alpha-hydroxylase, P-450a, were studied to understand the interaction of these hormone-mediated regulations in rats. In Western blots using anti-P-450a IgG, 1.7-fold higher content of P-450a was observed in livers of female than male adult rats, while no appreciable sex-related difference was detected in prepubertal rats and rats of 24 months of age. Treatment with n-propyl-2-thiouracil or thyroidectomy of male rats increased by 2-fold the hepatic content of P-450a, but neither regimen had a significant effect on the content in female rats. Levels of P-450a in both sexes of thyroidectomized rats were decreased by the supplementation of triiodothyronine (T3, 50 micrograms per kg, i.p. for 7 days) to levels similar to that observed in normal male rats. Hypophysectomy also caused an increase in microsomal P-450a content in male rats. Continuous infusion of human growth hormone, which mimicked the female secretion, further significantly increased the content in hypophysectomized rats to a level similar to that observed in normal female rats. In contrast, hepatic level of P-450a in hypophysectomized male and female rats was reduced by intermittent injection, which mimicked the male secretion. Clear suppression on the level of hepatic P-450a was also observed by the treatment of hypophysectomized rats with 5 or 50 micrograms/kg of T3 and of hGH-infused hypophysectomized rat with 50 micrograms/kg of T3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytostatic and growth-stimulating effects of alveolar macrophages of rats on tumor cells

Cytostatic and growth-stimulating effects of alveolar macrophages (AM) of rats on tumor cells were studied. The experimental results are summarized as follows. 1. The cytotoxicity of AM activated with BCG to tumor cells was increasing with the increase of effector cells/target cells (E/T) ratio. AM without the treatment with BCG expressed slight cytotoxicity to tumor cells at a high E/T, and growth-stimulating effect on tumor cells, at a low E/T. 2. AM after 24-hour culture had a lower manifestation of cytotoxicity to human lung adenocarcinoma cell line than that of AM without 24-hour culture, and had a growth-stimulating effect on B-16 cell line. 3. Cytostatic and growth-stimulating effects of AM without or with 24-hour culture were decreasing with the increase of irradiation doses.     

JQ-1 ameliorates schistosomiasis liver granuloma in mice by suppressing male and female reproductive systems and egg development of Schistosoma japonicum

Schistosomiasis is a serious and widespread parasitic disease caused by infection with Schistosoma. Because the parasite’s eggs are primarily responsible for schistosomiasis dissemination and pathogenesis, inhibiting egg production is a potential approach to control the spread and severity of the disease. The bromodomain and extra-terminal (BET) proteins represent promising targets for the development of epigenetic drugs against Schistosoma. JQ-1 is a selective inhibitor of the BET protein family. In the present study, JQ-1 was applied to S. japonicum in vitro. By using laser confocal scanning microscopy and EdU incorporation assays, we showed that application of JQ-1 to worms in vitro affected egg laying and the development of both the male and female reproductive systems. JQ-1 also inhibited the expression of the reproductive-related genes SjPlk1 and SjNanos1 in S. japonicum. Mice infected with S. japonicum were treated with JQ-1 during egg granuloma formation. JQ-1 treatment significantly reduced the size of the liver granulomas and levels of serum alanine aminotransferase and aspartate aminotransferase in mice and suppressed both egg laying and the development of male and female S. japonicum reproductive systems in vivo. Moreover, the mRNA expression levels of some proinflammatory cytokines were decreased in the parasites. Our findings suggest that JQ-1 treatment attenuates S. japonicum egg–induced hepatic granuloma due at least in part to suppressing the development of the reproductive system and egg production of S. japonicum. These findings further suggest that JQ-1 or other BET inhibitors warrant additional study as a new approach for the treatment or prevention of schistosomiasis.     

Is the removal of aboveground shrub biomass an effective technique to restore a shrub‐encroached grassland?

Encroachment of woody plants into grasslands is a global phenomenon that has substantial impacts on pastoral productivity and ecosystem services. Over the past half century, pastoralists and land management agencies have explored various options to control woody plants in order to improve ecosystem services in shrub‐encroached grasslands. We examined the effectiveness of controlling the encroachment of the shrub Caragana microphylla into grassland in Inner Mongolia, China. We cut and removed all of the aboveground biomass from 450 shrubs, predicting that the effectiveness of this technique to control shrubs would depend on shrub morphology. Specifically, we expected that larger shrubs with more biomass would be more difficult to kill by cutting than smaller shrubs. A year after treatment, we found that cutting killed only 11% of the 450 treated shrubs, and of these, three‐quarters of the locations that they occupied reverted to grasses and one‐quarter to bare soil. Shrubs that survived the cutting treatment produced more stems and leaf biomass, and therefore had a greater leaf to stem ratio. Shrubs that died after cutting had a lower crown area and basal area, and less stem biomass than shrubs that resprouted within 12 months of cutting. There were no effects of shrub height on the fate of treated shrubs. Cutting had no effect on understory plant cover or richness, but reproductive plants were taller under shrubs that were not cut. Overall, our study showed that removing aboveground shrub biomass by cutting is an ineffective technique for “restoring” the original grassland community unless shrubs are very small. Strategic targeting of small shrubs would be a more effective technique for controlling the spread of C. microphylla in the long term.     

滞育和非滞育棉铃虫前胸腺的形态解剖学比较研究

该文用解剖镜和电子显微镜对滞育和非滞育棉铃虫Helicoverpa armigera前胸腺的形态解剖结构进行了比较研究。结果发现滞育棉铃虫的前胸腺细胞及其细胞间隙相对较小,不易着色,细胞核规则,较小,细胞质中几乎见不到光滑内质网和粗面内质网,线粒体极少,这些观察到的现象充分说明滞育棉铃虫的前胸腺活性较低。     

皖南尖吻蝮蛇毒出血毒素Ⅳ的纯化与初步鉴定

从皖南尖吻蝮蛇（Ａｇｋｉｓｔｒｏｄｏｎａｃｕｔｕｓ）毒液中经ＤＥＡＥ－Ｓｅｐｈａｒｏｓｅ和ＳｅｐｈａｃｒｙｌＳ－２００两步凝胶柱层析首次纯化出一种中分子量出血毒素（简称ＡａＨⅣ）．经ＳＤＳ－ＰＡＧＥ和等电聚焦凝胶电泳测定其分子量为４４ｋＤ,等电点为ｐＨ５．０．从５００ｍｇ粗毒中可获得２０ｍｇＡａＨⅣ纯品．ＡａＨⅣ有较强的出血活性,最小出血剂量（ＭＨＤ）为０．４μｇ．     

Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae – Identification of LYS228

Metallo-β-lactamases (MBLs), such as New Delhi metallo-β-lactamase (NDM-1) have spread world-wide and present a serious threat. Expression of MBLs confers resistance in Gram-negative bacteria to all classes of β-lactam antibiotics, with the exception of monobactams, which are intrinsically stable to MBLs. However, existing first generation monobactam drugs like aztreonam have limited clinical utility against MBL-expressing strains because they are impacted by serine β-lactamases (SBLs), which are often co-expressed in clinical isolates. Here, we optimized novel monobactams for stability against SBLs, which led to the identification of LYS228 (compound 31). LYS228 is potent in the presence of all classes of β-lactamases and shows potent activity against carbapenem-resistant isolates of Enterobacteriaceae (CRE).