Induced osteoblast differentiation by amide derivatives of stilbene: The possible osteogenic agents

A series of amide derivatives of stilbene was synthesized and investigated for osteogenic activity. Out of sixteen, seven compounds viz 19c, 19g, 19i, 24b, 25a, 25c and 26a showed significant osteoblast differentiation within 1 pM–1 µM concentrations. Amongst all, 26a was identified as most active molecule which presented effective mineralization of osteoblasts and expression of mRNA of osteogenic marker gene such as BMP-2, ALP, and Runx-2 at 1 pM. In estrogen-deficient balb/c mice, 26a showed significant osteogenic activity at 5 mg-kg⁻¹ body weight dose. The protein expression study for estrogen receptors α and β (ER-α & ER-β) using mouse calvarial osteoblasts (MCOs) and molecular docking analyses showed preferential expression of ER-β by 26a indicating the possibility of ER-β mediated osteogenic activity of 26a.     

Novel class of benzimidazole-thiazole hybrids: The privileged scaffolds of potent anti-inflammatory activity with dual inhibition of cyclooxygenase and 15-lipoxygenase enzymes

The present study includes design and synthesis of new molecular hybrids of 2-methylthiobenzimidazole linked to various anti-inflammatory pharmacophores through 2-aminothiazole linker, to investigate the effect of such molecular variation on cyclooxygenase (COX) and 15-lipoxygenase (15-LOX) enzymes inhibition as well as in vivo anti-inflammatory activity. The chemical structures of new hybrids were confirmed using different spectroscopic tools and elemental analyses. Benzimidazole-thiazole hybrids linked to acetyl moiety 13, phenyl thiosemicarbazone 14, 1,3-thiazolines 15a-c and 4-thiazolidinone 16 exhibited significant COX-2 inhibition (IC₅₀ = 0.045–0.075 µM) with significant COX-2 selectivity indices (SI = 142–294). All hybrids revealed potent 15-LOX inhibitory activity (IC₅₀ = 1.67–6.56 µM). Benzimidazole-thiazole hybrid 15b was the most potent dual COX-2 (IC₅₀ = 0.045 µM, SI = 294) inhibitor approximate to celecoxib (COX-2; IC₅₀ = 0.045 µM, SI = 327), with double inhibitory activity versus 15-LOX enzyme (IC₅₀ = 1.67 µM) relative to quercetin (IC₅₀ = 3.34 µM). Three hybrids (14, 15b & 16) were selected for in vivo screening using carrageenan-induced paw edema method. Benzimidazole-thiazole hybrid linked to 4-thiazolidinone 16 showed the maximum edema inhibition at both 3 h and 4 h intervals as well (~119% and 102% relative to indomethacin, respectively). The gastric ulcerogenic effect of benzimidazole-thiazole hybrid 16 was estimated compared with indomethacin showing superior gastrointestinal safety profile. In bases of molecular modeling; all new active hybrids were subjected to docking simulation into active sites of COX-2 and 15-LOX enzymes to study the binding mode of these novel potent dual COX-2/15-LOX inhibitors.     

昆虫钠离子通道的研究进展

昆虫只有一个或两个电压门控钠离子通道α亚基基因,但两种转录后修饰(选择性剪切和RNA编辑)实现了昆虫钠离子通道的功能多样性。昆虫β辅助亚基TipE和TEH1-4在钠离子通道表达和调控中也起着重要作用。电压门控钠离子通道在动作电位的产生和传递中至关重要,是多种天然和人工合成神经毒素及杀虫剂的作用靶标,包括广泛使用的拟除虫菊酯类、茚虫威和氰氟虫腙等杀虫剂。其中,拟除虫菊酯类杀虫剂通过调控昆虫钠离子通道的失活和去激活,延长跨膜钠离子流的时间,引起神经兴奋性传导障碍;茚虫威和氰氟虫腙阻断昆虫中枢和外周神经系统神经元的动作电位传导,这些神经毒剂都能干扰昆虫钠离子通道的正常功能。昆虫钠离子通道一般存在两个拟除虫菊酯类杀虫剂结合位点,但不同物种钠离子通道与拟除虫菊酯的结合位点存在一定差异。据此,本文就昆虫钠离子通道及其与杀虫剂的相互作用加以综述,有望推动昆虫神经受体研究,且对鉴定昆虫抗药性相关突变位点和研发高效的杀虫剂均具有重要参考价值。     

Entomophagous insects – an introduction

This special issue contains papers presented at the 6th International Entomophagous Insects Conference. Entomophagous insects consume other insects. They are a fundamental component of ecosystems and are extensively used as biocontrol agents. The first article reviews the role of ladybirds in biological control and the second reviews the biological control of stink bugs. The following nine research articles cover the rearing, behavior, life history, and ecology of parasitoid and predator species.     

预防造影剂肾病水化时机选择的Meta分析

目的评价预防造影剂肾病(CIN)不同口服水化时机选择的效果,为降低CIN发生率提供依据。方法运用计算机检索PubMed、EMbase、The Cochrane Library、中国知网、万方数据库、维普数据库以及中国生物医学文献数据库关于口服水化预防造影剂肾病的随机对照试验(RCT),检索时间从建库至2020年9月。由2名研究人员独立筛选文献、提取基本资料并根据Cochrane手册评价文献的质量,采用RevMan 5.3软件进行Meta分析。结果共纳入11个CRT研究,1927例患者。Meta分析结果显示,术后6 h内定时定量饮水可降低CIN的发病率[RR=0.33,95%CI(0.20,0.54),P<0.01],同时定时定量饮水可减少尿潴留的发生[RR=0.48,95%CI(0.30,0.77),P=0.003]及胃部不适感[RR=0.57,95%CI(0.38,0.85),P=0.006]。结论有计划定时定量饮水进行水化疗法可降低造影剂肾病的发生率,减少了尿潴留的发生及胃部不适感。     

The tyrosine kinase v-Src modifies cytotoxicities of anticancer drugs targeting cell division

v-Src oncogene causes cell transformation through its strong tyrosine kinase activity. We have revealed that v-Src-mediated cell transformation occurs at a low frequency and it is attributed to mitotic abnormalities-mediated chromosome instability. v-Src directly phosphorylates Tyr-15 of cyclin-dependent kinase 1 (CDK1), thereby causing mitotic slippage and reduction in Eg5 inhibitor cytotoxicity. However, it is not clear whether v-Src modifies cytotoxicities of the other anticancer drugs targeting cell division. In this study, we found that v-Src restores cancer cell viability reduced by various microtubule-targeting agents (MTAs), although v-Src does not alter cytotoxicity of DNA-damaging anticancer drugs. v-Src causes mitotic slippage of MTAs-treated cells, consequently generating proliferating tetraploid cells. We further demonstrate that v-Src also restores cell viability reduced by a polo-like kinase 1 (PLK1) inhibitor. Interestingly, treatment with Aurora kinase inhibitor strongly induces cell death when cells express v-Src. These results suggest that the v-Src modifies cytotoxicities of anticancer drugs targeting cell division. Highly activated Src-induced resistance to MTAs through mitotic slippage might have a risk to enhance the malignancy of cancer cells through the increase in chromosome instability upon chemotherapy using MTAs.     

Cyberlindnera fabianii: primer aislamiento clínico en Chile

BackgroundAlthough considered an unusual etiological agent, Cyberlindnera (Candida) fabianii has been related to septicemia in several reports in recent years. Its doubtful or uncertain identification when using tests such as CHROMagar Candida, API® Candida, API® ID32C or VITEK® MS, leads to an underestimation of the cases produced by this yeast.AimsTo report the first isolation of C. fabianii in Chile and its identification.MethodsThe sequencing of the internal transcribed spacer region (ITS) was performed. Antifungal susceptibility profiles were obtained by means of the broth microdilution technique.ResultsThe identification was only reached by sequencing the ITS regions, which shows the limited usefulness of the conventional techniques in the identification of some yeast species. A dendrogram shows the phylogenetic relationship of the isolated strain with some other yeast species.ConclusionIn the identification of fastidious microorganisms or microorganisms whose identification is not completely reliable when using classical or even advanced methodologies, such as mass spectrometry, sequencing techniques are essential.     

Antimycobacterial activity: synthesis of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues

In this study, a series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized and evaluated for antimycobacterial activity against Mycobacterium tuberculosis (MTB) H₃₇Rv and isoniazid resistant M. tuberculosis (INHR-MTB). All the newly synthesized compounds were showing moderate to high inhibitory activities. The compound 6,7-dimethoxy-3-(4-chloro phenyl)-4H-indeno[1,2-c]isoxazole (4b) was found to be the most promising compound, active against MTB H₃₇Rv and INHR-MTB with minimum inhibitory concentrations of 0.22 and 0.34 μM.     

Synthesis and evaluation of the antiproliferative activity of novel isoindolo[2,1-a]quinoxaline and indolo[1,2-a]quinoxaline derivatives

A novel series of isoindolo[2,1-a]quinoxaline and indolo[1,2-a]quinoxaline derivatives was synthesized and evaluated in vitro against various human cancer cell lines for antiproliferative activity. These new compounds displayed activity against leukemia and breast cancer cell lines in the 3- to 18-µM concentration range.