Selenium in combination with a tomato lipid extract as a therapy for benign prostatic hyperplasia and its alterations in rats with induced BPH

Benign prostatic hyperplasia (BPH) is the most common adenoma in old men. Tomatoes are a rich source of bioactive compounds that, as well as selenium (Se), possess antioxidant and antiproliferative activity. The aim was to evaluate the therapeutic effect of Se in combination with a tomato extract in aged rats with BPH. Aged male Wistar rats were divided in the following groups (n = 10 rats/group): Control (C), BPH, BPH + Finasteride (BPH + F), BPH + Tomato Lipidic Extract (BPH + E), BPH + Selenium (BPH + S) and BPH plus E plus S (BPH + E + S). After 4 weeks of treatment, prostate weight, diuresis, antioxidants enzymes, prooxidants and inflammatory markers, growth factors and androgens were determined. BPH + E + S reduced prostate weight by 59.29% and inhibited growth by 99.35% compared to BPH + F which only decreased weight and inhibited growth by 15.31% and 57.54%, respectively. Prooxidant markers were higher with BPH + F (49.4% higher vs. BPH), but BPH + E + S decreased these markers (94.27% vs. BPH) and increased antioxidant activity. Finally, diuresis was higher with the BPH + E + S combination and markers of inflammation and growth factors were significantly lower with respect to BPH + F. Our findings provide a beneficial and protective therapeutic option of E + S directed against androgens, oxidative stress and inflammation that regulates cell proliferation in the prostate gland.     

PYK2 is overexpressed in chronic lymphocytic leukaemia: A potential new therapeutic target

Chronic Lymphocytic Leukaemia (CLL) is the most common adult B-cell leukaemia and despite improvement in patients' outcome, following the use of targeted therapies, it remains incurable. CLL supportive microenvironment plays a key role in both CLL progression and drug resistance through signals that can be sensed by the main components of the focal adhesion complex, such as FAK and PYK2 kinases. Dysregulations of both kinases have been observed in several metastatic cancers, but their role in haematological malignancies is still poorly defined. We characterized FAK and PYK2 expression and observed that PYK2 expression is higher in leukaemic B cells and its overexpression significantly correlates with their malignant transformation. When targeting both FAK and PYK2 with the specific inhibitor defactinib, we observed a dose–response effect on CLL cells viability and survival. In vivo treatment of a CLL mouse model showed a decrease of the leukaemic clone in all the lymphoid organs along with a significant reduction of macrophages and of the spleen weight and size. Our results first define a possible prognostic value for PYK2 in CLL, and show that both FAK and PYK2 might become putative targets for both CLL and its microenvironment (e.g. macrophages), thus paving the way to an innovative therapeutic strategy.     

Effects of Sirolimus treatment on patients with β-Thalassemia: Lymphocyte immunophenotype and biological activity of memory CD4+ and CD8+ T cells

Inhibitors of the mammalian target of rapamycin (mTOR) have been proposed to improve vaccine responses, especially in the elderly. Accordingly, testing mTOR inhibitors (such as Sirolimus) and other geroprotective drugs might be considered a key strategy to improve overall health resilience of aged populations. In this respect, Sirolimus (also known as rapamycin) is of great interest, in consideration of the fact that it is extensively used in routine therapy and in clinical studies for the treatment of several diseases. Recently, Sirolimus has been considered in laboratory and clinical studies aimed to find novel protocols for the therapy of hemoglobinopathies (e.g. β-Thalassemia). The objective of the present study was to analyse the activity of CD4⁺ and CD8⁺ T cells in β-Thalassemia patients treated with Sirolimus, taking advantages from the availability of cellular samples of the NCT03877809 clinical trial. The approach was to verify IFN-γ releases following stimulation of peripheral blood mononuclear cells (PBMCs) to stimulatory CEF and CEFTA peptide pools, stimulatory for CD4⁺ and CD8⁺ T cells, respectively. The main results of the present study are that treatment of β-Thalassemia patients with Sirolimus has a positive impact on the biological activity and number of memory CD4⁺ and CD8⁺ T cells releasing IFN-γ following stimulation with antigenic stimuli present in immunological memory. These data are to our knowledge novel and in our opinion of interest, in consideration of the fact that β-Thalassemia patients are considered prone to immune deficiency.     

The role of non-natural foods in the nutritional strategies of monkeys in a human-modified mosaic landscape

Many tropical animals inhabit mosaic landscapes including human-modified habitat. In such landscapes, animals commonly adjust feeding behavior, and may incorporate non-natural foods. These behavioral shifts can influence consumers' nutritional states, with implications for population persistence. However, few studies have addressed the nutritional role of non-natural food. We examined nutritional ecology of wild blue monkeys to understand how dietary habits related to non-natural foods might support population persistence in a mosaic landscape. We documented prevalence and nutritional composition of non-natural foods in monkey diets to assess how habitat use influenced their consumption, and their contribution to nutritional strategies. While most energy and macronutrients came from natural foods, subjects focused non-natural feeding activity on five exotic plants, and averaged about a third of daily calories from non-natural foods. Most non-natural food calories came from non-structural carbohydrates and least from protein. Consumption of non-natural foods related to time in human-modified habitats, which two groups used non-randomly. Non-natural and natural foods were similar in nutrients, and the amount of non-natural food consumed drove variation in nutritional strategy. When more daily calories came from non-natural foods, females consumed a higher ratio of non-protein energy to protein (NPE:P). Females also prioritized protein while allowing NPE:P to vary, increasing NPE while capitalizing on non-natural foods. Overall, these tropical mammals achieved a similar nutrient balance regardless of their intake of non-natural foods. Forest and forest-adjacent areas with non-natural vegetation may provide adequate nutrient access for consumers, and thus contribute to wildlife conservation in mosaic tropical landscapes.     

Molecular mimicry in Lyme disease: monoclonal antibody H9724 to b. burgdorferi flagellin specifically detects chaperonin-HSP60

A monoclonal antibody (H9724), specific for the 41-kDa flagellar protein of the Lyme disease pathogen Borrelia burgdorferi, cross-reacts with human axons and detects one major protein in human neuroblastoma cell extracts. The homologous cross-reacting protein has now been isolated from calf adrenal and identified as chaperonin-HSP60 by N-terminal sequencing.     

色氨酸阻遏物与其操纵基因复合物的圆二色性研究

用圆二色性谱来确定色氨酸阻遏物与其操纵基因复合物在溶液中的构象变化。色氨酸阻遏物的圆二色性图谱表明它是一种富含α螺旋的蛋白质,通过比较加入Ｌ－Ｔｒｐ前和后的圆二色性谱,发现活性的与非活性的色酸阻遏物二级结构变化很小,ｔｒｐ Ｐ／Ｏ的圆二色性谱与它的单健、双链理论计算曲线对比,可近拟推测操纵基因在溶液中的存在状态。用色氨酸阻遏物对ｔｒｐ Ｐ／Ｏ进行确定,可以从中找出蛋白质与核酸结合的平衡点。从平衡时     

用胆固醇代谢的房室模型速率系数来分析动脉粥样硬化程度

理论上认为胆固醇逆向转运的速率与动脉粥样硬化程序呈负相关。但目前尚无完善的测试血浆脂蛋白－胆固醇体内代谢的方法。我们运用同位素＾３Ｈ－胆固醇示踪方法,建立房室模型,选取健康兔与ＡＳ兔对照,研究血浆脂蛋白转运胆固醇能力的差异,并结合ＡＳ兔主动脉斑块程度对比,结果验证了上述理论,此法如改用短半衰期同位素或稳定性同位素标记的胆固醇,就可用于人体,这可为临床判断ＡＳ程度提供一种无创性的新方法。     

平截独活的香豆素成分

从四川省汶川县产平截独活Heracleum vicinum根的乙醇提取物中分离鉴定了6个成分,分别为虎耳草素(pimpinellin)(1),异佛手柑内酯(2),6-甲氧基当归素(sphondin)(3)。佛手柑内酯(bergapten)(4),异虎耳草素(isopimpincllin)(5),falcarindi01)(6).     

Environmentally-Friendly Pesticidal Activities of Callicarpa and Karomia Essential Oils from Vietnam and Their Microemulsions

There is an ongoing interest to identify alternative pesticidal agents to avoid the chronic problems associated with synthetic pesticides. Essential oils have shown promise as botanical pest control agents. In the present study, the essential oils of four members of the Lamiaceae (Callicarpa candicans, C. erioclona, C. macrophylla, and Karomia fragrans; Vietnamese names: Nàng nàng, Tu châu lông mem, Tu châu lá to and Cà diện, respectively), obtained from wild populations in Vietnam, have been obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry. The essential oils were formulated into microemulsions and the essential oils and their microemulsions were screened for mosquito larvicidal activity against Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and for molluscicidal activity against Pomacea canaliculata. Atractylone and (E)-caryophyllene dominated the volatiles of C. candicans (CCEO) and C. erioclona (CEEO), while the major component in C. macrophylla (CMEO) and K. fragrans (KFEO) was (E)-caryophyllene. The essential oils and microemulsions of both C. candicans and C. erioclona exhibited excellent larvicidal activity against all three mosquito species (Ae. aegypti, Ae. albopictus, and Cx. quinquefasciatus) with LC₅₀ values <10 μg/mL. Additionally, the larvicidal activity of the microemulsions were significantly improved compared with their free essential oils, especially for C. candicans and C. erioclona. All four essential oils and their microemulsions showed excellent molluscicidal activity with LC₅₀ <10 μg/mL. In most cases, the essential oils and microemulsions showed greater pesticidal activity against target organisms than the non-target freshwater fish, Oreochromis niloticus. The in silico studies on physicochemical and ADMET properties of the major components in the studied essential oils were also investigated and most of the compounds possessed a favorable ADMET profile. Computational modeling studies of the studied compounds demonstrated a favorable binding interaction with the mosquito odorant-binding protein target and support atractylone, β-selinene, and caryophyllene oxide as potential inhibitors. Based on the observed pesticidal activities of the essential oils and their microemulsions, the Callicarpa species and K. fragrans should be considered for potential cultivation and further exploration as botanical pesticidal agents.