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51.
Leo Mandić Patricia Benčić Kata Mlinarić-Majerski Sandra Liekens Robert Snoeck Graciela Andrei Marijeta Kralj Nikola Basarić 《Archiv der Pharmazie》2020,353(6):2000024
In this study, three groups of adamantylphthalimides, bearing different substituents at the phthalimide moiety, N-(4′-R2)phthalimidoadamantanes ( 1 – 7 ), 3-[N-(4′-R2)phthalimido]-1-adamantanols ( 8 – 10 ), and 3-[N-(4′-R2)phthalimido]adamantane-1-carboxylic acids ( 11 – 15 ), were synthesized and screened against tumor cells and viruses. The most potent compounds are not substituted at the adamantane and bear an OH or NH2 substituent at the phthalimide (compounds 3 and 5 ). The antiproliferative activities of compounds 3 and 5 are in the micromolar range, much higher than the one of thalidomide. A minor antiviral activity against cytomegalovirus and varicella-zoster virus was found for compounds 3 and 5 , but these compounds lacked selectivity. The results presented are important for the rational design of the next-generation compounds with anticancer and antiviral activities. 相似文献
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Sebastian A. Andrei Eline Sijbesma Michael Hann Jeremy Davis Gavin O’Mahony Matthew W. D. Perry 《Expert opinion on drug discovery》2017,12(9):925-940
Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery.Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach.Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts. 相似文献
54.
Shiri Sherf Dagan Shira Zelber-Sagi Muriel Webb Andrei Keidar Asnat Raziel Nasser Sakran David Goitein Oren Shibolet 《Obesity surgery》2016,26(9):2119-2126
Background
Two main causes for nutrient deficiencies following bariatric surgery (BS) are pre-operative deficiencies and favoring foods with high-energy density and poor micronutrient content. The aims of this study were to evaluate nutritional status and gender differences and the prevalence of nutritional deficiencies among candidates for laparoscopic sleeve gastrectomy (LSG) surgery.Methods
A cross-sectional analysis of pre-surgery data collected as part of a randomized clinical trial on 100 morbidly obese patients with non-alcoholic fatty liver disease (NAFLD) admitted to LSG surgery at Assuta Medical Center between February 2014 and January 2015. Anthropometrics, food intake, and fasting blood tests were evaluated during the baseline visit.Results
One-hundred patients completed the pre-operative measurements (60 % female) with a mean age of 41.9?±?9.8 years and a mean BMI of 42.3?±?4.7 kg/m2. Pre-operatively, deficiencies for iron, ferritin, folic acid, vitamin B1, vitamin B12, vitamin D, and hemoglobin were 6, 1, 1, 6, 0, 22, and 6 %, respectively. Pre-surgery, mean energy, protein, fat, and carbohydrate intake were 2710.7?±?1275.7 kcal/day, 114.2?±?48.5, 110.6?±?54.5, and 321.6?±?176.1 gr/day, respectively. The intakes for iron, calcium, folic acid, vitamin B12, and vitamin B1 were below the Dietary Reference Intake (DRI) recommendations for 46, 48, 58, 14, and 34 % of the study population, respectively.Conclusion
We found a low prevalence of nutritional deficiencies pre-operatively except for vitamin D. Most micronutrient intake did not reach the DRI recommendations, despite high-caloric and macronutrient intake indicating a poor dietary quality.55.
Diabetes mellitus and obesity, which is a major risk factor in the development of type 2 diabetes mellitus, have reached epidemic proportions worldwide including the USA. The current statistics and forecasts, both short- and long-term, are alarming and predict severe problems in the near future. Therefore, there is a race for developing new compounds, discovering new receptors, or finding alternative solutions to prevent and/or treat the symptoms and complications related to obesity and diabetes mellitus. It is well demonstrated that members of the transient receptor potential (TRP) superfamily play a crucial role in a variety of biological functions both in health and disease. In the recent years, transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) were shown to have beneficial effects on whole body metabolism including glucose homeostasis. TRPV1 and TRPA1 have been associated with control of weight, pancreatic function, hormone secretion, thermogenesis, and neuronal function, which suggest a potential therapeutic value of these channels. This review summarizes recent findings regarding TRPV1 and TRPA1 in association with whole body metabolism with emphasis on obese and diabetic conditions. 相似文献
56.
57.
Moving towards individualized performance models 总被引:1,自引:1,他引:0
58.
Gorbachev AV Gasparian AV Gurova KV Gudkov AV Fairchild RL 《European journal of immunology》2007,37(8):2257-2267
Quinacrine (QC) is an anti-inflammatory drug that has been used for the treatment of malaria and rheumatoid diseases. The mechanism(s) underlying the anti-inflammatory activity of QC remains poorly understood. We recently reported the QC-mediated inhibition of the NF-kappaB pathway using an in vitro model. To test this potential mechanism in vivo, we used the contact hypersensitivity response (CHS) to chemical allergen sensitization and challenge in mice as a model of skin inflammation. The results indicated that QC treatment inhibited NF-kappaB activation in the skin during allergen sensitization. This inhibition was reflected by decreased mRNA expression and protein production of the NF-kappaB-dependent cytokines TNF-alpha and IL-1beta and the chemokine CCL21 in the skin. The decreases in these cytokines resulted in reduced migration of allergen-presenting dendritic cells from the skin into skin-draining lymph nodes and markedly decreased activation of effector CD8+ T cells for the CHS response to allergen challenge (inhibitory concentration 50% or IC50 was 55 mg/kg). These findings reveal a previously unrecognized mechanism of QC-mediated inhibition of inflammation. 相似文献
59.
Agustín Estrada-Peña Sally Cutler Aleksandar Potkonjak Muriel Vassier-Tussaut Wim Van Bortel Hervé Zeller Natalia Fernández-Ruiz Andrei Daniel Mihalca 《International journal of health geographics》2018,17(1):41
Background
The bacteria of the group Borrelia burgdorferi s.l. are the etiological agents of Lyme borreliosis in humans, transmitted by bites of ticks. Improvement of control measures requires a solid framework of the environmental traits driving its prevalence in ticks.Methods
We updated a previous meta-analysis of the reported prevalence of Borrelia burgdorferi s.l. in questing nymphs of Ixodes ricinus with a literature search from January 2010–June 2017. This resulted in 195 new papers providing the prevalence of Bb for 926 geo-referenced records. Previously obtained data (878 records, years 2000–2010) were appended for modelling. The complete dataset contains data from 82,004 questing nymphs, resulting in 558 records of B. afzelii, 404 of B. burgdorferi s.s. (only 80 after the year 2010), 552 of B. garinii, 78 of B. lusitaniae, 61 of B. spielmanii, and 373 of B. valaisiana. We associated the records with explicit coordinates to environmental conditions and to a categorical definition of European landscapes (LANMAP2) looking for a precise definition of the environmental niche of the most reported species of the pathogen, using models based on different classification methods.Results
The most commonly reported species are B. afzelii, B. garinii and B. valaisiana largely overlapping across Europe. Prevalence in ticks is associated with portions of the environmental niche. Highest prevalence occurs in areas of 280°–290° (Kelvin) of mean annual temperature experiencing a small amplitude, steady spring slope, together with high mean values and a moderate spring rise of vegetation vigor. Low prevalence occurs in sites with low and a noteworthy annual amplitude of temperature and the Normalized Difference Vegetation Index (colder areas with abrupt annual changes of vegetation). Models based on support vector machines provided a correct classification rate of the habitat and prevalence of 89.5%. These results confirm the association of prevalence of the three most commonly reported species of B. burgdorferi s.l. in Europe to parts of the environmental niche and provide a statistically tractable framework for analyzing trends under scenarios of climate change.60.
Lopez-Ramirez Felipe Gushchin Vadim Sittig Michelle King Mary Caitlin Baron Ekaterina Nikiforchin Andrei Nieroda Carol Sardi Armando 《Annals of surgical oncology》2022,29(6):3404-3404
Annals of Surgical Oncology - 相似文献