Antiproliferative Potential of Olneya tesota PF2 Lectin in Human Acute Monocytic Leukemia Cells

Acute monocytic leukemia is a type of myeloid leukemia that develops in monocytes. The current clinical therapies for leukemia are unsatisfactory due to their side effects and nonspecificity toward target cells. Some lectins display antitumor activity and may specifically recognize cancer cells by binding to carbohydrate structures on their surface. Therefore, this study evaluated the response of the human monocytic leukemia cell lines THP-1 to the Olneya tesota PF2 lectin. The induction of apoptosis and reactive oxygen species production in PF2-treated cells was evaluated by flow cytometry, and the lectin-THP-1 cell interaction and mitochondrial membrane potential were evaluated by confocal fluorescence microscopy. PF2 genotoxicity was evaluated by DNA fragmentation analysis via gel electrophoresis. The results showed that PF2 binds to THP-1 cells, triggers apoptosis and DNA degradation, changes the mitochondrial membrane potential, and increases reactive oxygen species levels in PF2-treated THP-1 cells. These results suggest the potential use of PF2 for developing alternative anticancer treatments with enhanced specificity.     

Diversity and antimicrobial activity of endophytic fungi isolated from Nyctanthes arbor-tristis, a well-known medicinal plant of India

Endophytic fungi from Nyctanthes arbor-tristis were isolated and evaluated for their antimicrobial activity. A total of 19 endophytic fungi were isolated from 400 segments of healthy leaf and stem tissues of N. arbor-tristis. Eighteen endophytic fungi were obtained from leaf, while only ten from stem. Alternaria alternata had the highest colonization frequency (15.0%) in leaf, whereas Cladosporium cladosporioides ranked first in stem with a colonization frequency of 12%. The diversity and species richness were found higher in leaf tissues than in stem. The similarity indices between leaf and stem were 0.473 for Jaccard’s and 0.642 for the Sorenson index, respectively. Of 16, 12 (75%) endophytic fungal extracts showed antibacterial activity against either one or more pathogenic bacteria. The endophytic Nigrospora oryzae showed maximum inhibition against Shigella sp. and Pseudomonas aeruginosa. The leaf endophytes Colletotrichum dematium and Chaetomium globosum exhibited a broad range of anibacterial activity and were active against Shigella flexnii, Shigella boydii, Salmonella enteritidis, Salmonella paratyphi, and P. aeruginosa. Nine out of 16 (56.25%) endophytic fungi exhibited antifungal activity to one or more fungal pathogens. Colletotrichum dematium inhibited 55.87% of the radial growth of the phytopathogen Curvularia lunata. The antimicrobial activity of these endophytic microorganisms could be exploited in the biotechnological, medicinal, and agricultural industries.     

草酸复合剂对苹果清洗效果及生理特征的影响

以'红富士'苹果为试材,研究了以草酸(OA)为主剂,二氧化氯(ClO2)、氯化钠(NaCl)等为辅剂的清洗剂(10.0 g·L-1 +10.0 g·L-1 NaCl+9 mg·kg-1 OA ClO2+0.02%吐温-20)对果实的清洗效果及采后生理的影响.结果表明:草酸复合清洗剂对'红富士'苹果表面的农药、重金属、菌落的去除率分别达76.39%～83.24%、62.48%～91.29%和80.64%;在(0±1)℃冷藏条件下,草酸复合清洗剂能显著抑制'红富士'苹果呼吸作用和乙烯释放,延缓二者跃变高峰的出现,同时提高了果实超氧化物歧化酶(SOD)、过氧化物酶(POD)和过氧化氢酶(CAT)活性,有效抑制果实丙二醛(MDA)含量和相对膜透性的升高,从而降低膜脂过氧化程度.研究发现,草酸复合清洗剂既能有效清除苹果表面农药、重金属残留和菌落,又能调控果实的呼吸作用和活性氧代谢等过程来明显延缓采后果实的衰老.     

Evaluation of Streptomyces sp. strain g10 for suppression of Fusarium wilt and rhizosphere colonization in pot-grown banana plantlets

Streptomyces sp. strain g10 exhibited strong antagonism towards Fusarium oxysporum f.sp. cubense (Foc) races 1, 2 and 4 in plate assays by producing extracellular antifungal metabolites. Treating the planting hole and roots of 4-week-old tissue-culture-derived Novaria banana plantlets with strain g10 suspension (10⁸ cfu/ml), significantly (P<0.05) reduced wilt severity when the plantlets were inoculated with 10⁴ spores/ml Foc race 4. The final disease severity index for leaf symptom (LSI) and rhizome discoloration (RDI) was reduced about 47 and 53%, respectively, in strain g10-treated plantlets compared to untreated plantlets. Reduction in disease incidence was not significant (P<0.05) when plantlets were inoculated with a higher concentration (10⁶ spores/ml) of Foc race 4. Rhizosphere population of strain g10 showed significant (P=0.05) increase of more than 2-fold at the end of the 3rd week compared to the 2nd week after soil amendment with the antagonist. Although the level dropped, the rhizosphere population at the end of the 6th week was still nearly 2-fold higher than the level detected after 2 weeks. In contrast, the root-free population declined significantly (P=0.05), nearly 4-fold after 6 weeks when compared to the level detected after 2 weeks. Neither growth-inhibiting nor growth-stimulating effects were observed in plantlets grown in strain g10-amended soil.     

A specific plasminogen activator inhibitor‐1 antagonist derived from inactivated urokinase

Fibrinolysis is a process responsible for the dissolution of formed thrombi to re‐establish blood flow after thrombus formation. Plasminogen activator inhibitor‐1 (PAI‐1) inhibits urokinase‐type and tissue‐type plasminogen activator (uPA and tPA) and is the major negative regulator of fibrinolysis. Inhibition of PAI‐1 activity prevents thrombosis and accelerates fibrinolysis. However, a specific antagonist of PAI‐1 is currently unavailable for therapeutic use. We screened a panel of uPA variants with mutations at and near the active site to maximize their binding to PAI‐1 and identified a potent PAI‐1 antagonist, PAItrap. PAItrap is the serine protease domain of urokinase containing active‐site mutation (S195A) and four additional mutations (G37bR–R217L–C122A–N145Q). PAItrap inhibits human recombinant PAI‐1 with high potency (K_d = 0.15 nM) and high specificity. In vitro using human plasma, PAItrap showed significant thrombolytic activity by inhibiting endogenous PAI‐1. In addition, PAItrap inhibits both human and murine PAI‐1, allowing the evaluation in murine models. In vivo, using a laser‐induced thrombosis mouse model in which thrombus formation and fibrinolysis are monitored by intravital microscopy, PAItrap reduced fibrin generation and inhibited platelet accumulation following vascular injury. Therefore, this work demonstrates the feasibility to generate PAI‐1 inhibitors using inactivated urokinase.     

空间修复与公共空间更新的行动主义— 一个公共性与自主性的理论综述

从空间修复与微更新视角,将公共性理论、行动主义理论结合并融入学科自主性的讨论之中,从行动者网络的角度形成一个公共领域的能动性网络批判性框架,检视与评价社会复愈的著名案例,以期设计行业以此为参考,助力现行国家推行的基层自治、城市双修和社区微更新等空间实践。同时,也系统性地总结提出了一种基于全球在地化现实来拓宽学科自主性的可能与范式。     

Bottom‐up effect of host plants on life‐history characteristics of Aphidoletes aphidimyza feeding on Aphis gossypii

The predatory midge Aphidoletes aphidimyza (Rondani) (Diptera: Cecidomyiidae) is widely used for the control of Aphis spp. in many agricultural systems. We aimed to determine the most suitable host plant for rearing the predatory midges on the prey Aphis gossypii Glover (Hemiptera: Aphididae). Six host plants were selected: cucumber (Cucumis sativus L. cv. Beith Alpha), tomato (Solanum lycopersicum L. cv. Falat111), eggplant (Solanum melongena L. cv. Yummy), pepper (Capsicum annuum L. cv. Bertene) (all Solanaceae), okra [Abelmoschus esculentus (L.) Moensch cv. Clemson Spineless] (Malvaceae), and squash (Cucurbita pepo L. cv. Hybrid rajai) (Cucurbitaceae). Some physical traits (length and density of trichomes) and chemical attributes (nitrogen content) of prey host plants were investigated. The results showed that prey host plants differed significantly in their effect on fitness of the predator. The shortest immature development time (18.07 ± 0.257 days), the longest female adult longevity (7.5 ± 0.18 days), and the highest fecundity (89 eggs/female) of A. aphidimyza were found with squash as prey food. The highest intrinsic rate of increase (0.171 ± 0.009 day^?1) and also the shortest mean generation time (22.4 ± 0.32 days) were also obtained when A. aphidimyza fed on A. gossypii reared on squash. Canonical correlation analysis (CCA) approved the correlation between life‐history traits of A. aphidimyza and characteristics of prey host plants. The suitability of squash for rearing A. aphidimyza can be attributed to the higher nitrogen content, longer trichomes, and relatively high density of trichomes, which provided a better environment for A. gossypii and indirectly favored A. aphidimyza. This study showed that squash is the most suitable host plant for rearing A. aphidimyza feeding on A. gossypii.     

CONTRIBUTION OF CIRCADIAN PHYSIOLOGY AND SLEEP HOMEOSTASIS TO AGE-RELATED CHANGES IN HUMAN SLEEP

The circadian pacemaker and sleep homeostasis play pivotal roles in vigilance state control. It has been hypothesized that age-related changes in the human circadian pacemaker, as well as sleep homeostatic mechanisms, contribute to the hallmarks of age-related changes in sleep, that is, earlier wake time and reduced sleep consolidation. Assessments of circadian parameters in healthy young (～20–30 years old) and older people (～65–75 years old)—in the absence of the confounding effects of sleep, changes in posture, and light exposure—have demonstrated that an earlier wake time in older people is accompanied by about a 1h advance of the rhythms of core body temperature and melatonin. In addition, older people wake up at an earlier circadian phase of the body temperature and plasma melatonin rhythm. The amplitude of the endogenous circadian component of the core body temperature rhythm assessed during constant routine and forced desynchrony protocols is reduced by 20–30% in older people. Recent assessments of the intrinsic period of the human circadian pacemaker in the absence of the confounding effects of light revealed no age-related reduction of this parameter in both sighted and blind individuals. Wake maintenance and sleep initiation are not markedly affected by age except that sleep latencies are longer in older people when sleep initiation is attempted in the early morning. In contrast, major age-related reductions in the consolidation and duration of sleep occur at all circadian phases. Sleep of older people is particularly disrupted when scheduled on the rising limb of the temperature rhythm, indicating that the sleep of older people is more susceptible to arousal signals genernpated by the circadian pacemaker. Sleep-homeostatic mechanisms, as assayed by the sleep-deprivation–induced increase of EEG slow-wave activity (SWA), are operative in older people, although during both baseline sleep and recovery sleep SWA in older people remains at lower levels. The internal circadian phase advance of awakening, as well as the age-related reduction in sleep consolidation, appears related to an age-related reduction in the promotion of sleep by the circadian pacemaker during the biological night in combination with a reduced homeostatic pressure for sleep. Early morning light exposure associated with this advance of awakening in older people could reinforce the advanced circadian phase. Quantification of the interaction between sleep homeostasis and circadian rhythmicity contributes to understanding age-related changes in sleep timing and quality. (Chronobiology International, 17(3), 285–311, 2000)     

A p7 Ion Channel-derived Peptide Inhibits Hepatitis C Virus Infection in Vitro

Viral infection is an early stage of its life cycle and represents a promising target for antiviral drug development. Here we designed and characterized three peptide inhibitors of hepatitis C virus (HCV) infection based on the structural features of the membrane-associated p7 polypeptide of HCV. The three peptides exhibited low toxicity and high stability while potently inhibiting initial HCV infection and suppressed established HCV infection at non-cytotoxic concentrations in vitro. The most efficient peptide (designated H2-3), which is derived from the H2 helical region of HCV p7 ion channel, inhibited HCV infection by inactivating both intracellular and extracellular viral particles. The H2-3 peptide inactivated free HCV with an EC₅₀ (50% effective concentration) of 82.11 nm, which is >1000-fold lower than the CC₅₀ (50% cytotoxic concentration) of Huh7.5.1 cells. H2-3 peptide also bound to cell membrane and protected host cells from viral infection. The peptide H2-3 did not alter the normal electrophysiological profile of the p7 ion channel or block viral release from Huh7.5.1 cells. Our work highlights a new anti-viral peptide design strategy based on ion channel, giving the possibility that ion channels are potential resources to generate antiviral peptides.