Synthesis, structural characterization and biological evaluation of 40-C-methyl- and phenyl-dioxolane pyrimidine and purine nucleosides

Silvia Franchini,Umberto M. Battisti,Claudia Sorbi,Annalisa Tait,Andrea Cornia,정낙신,이상국,송자영,Roberta Loddo,Silvia Madeddu,Giuseppina Sanna,Livio Brasili 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.5

Nucleoside analogues play an important role inantiviral, antibacterial and antineoplastic chemotherapy. Herein we report the synthesis, structural characterizationand biological activity of some 40-C-methyl- and -phenyldioxolane-based nucleosides. In particular, a and banomers of all natural nucleosides were obtained andcharacterized by NMR, HR-MS and X-ray crystallography. The compounds were tested for antimicrobial activityagainst some representative human pathogenic fungi, bacteriaand viruses. Antitumor activity was evaluated in alarge variety of human cancer cell-lines. Although most ofthe compounds showed non-significant activity, 23aweakly inhibited HIV-1 multiplication. Moreover, 22a and32a demonstrated a residual antineoplastic activity, interestinglylinked to the unnatural a configuration. Theseresults may provide structural insights for the design ofactive antiviral and antitumor agents.

Intraumbilical versus intramuscular oxytocin in the management of the third stage of labor

Silvia Waleska Bu,César Alas-Pineda,David Aguilar-Andino,Dalton Argean Norwood,Kristhel Gaitán-Zambrano,Mario Pinto-Romero 대한산부인과학회 2023 Obstetrics & Gynecology Science Vol.66 No.2

ObjectiveTo compare the effect of intraumbilical vein oxytocin injection with standard management in reducing blood loss during the third and fourth stages of labor. Acute complications threaten the mother’s life during the third and fourth stages of labor. The most common complication is postpartum hemorrhage, which remains a leading cause of maternal mortality, particularly in developing countries. MethodsA randomized controlled trial was conducted in the Gynecology and Obstetrics Department of Leonardo Mart?nez Valenzuela Hospital from January to June 2021. A probabilistic sample was used: 332 pregnant patients were enrolled in the study and randomized into the case (166 patients) and control (166 patients) groups. The volume of blood lost was compared between the groups. ResultsThe median estimated blood loss was 120 mL (interquartile range [IQR], 80-218.75 mL). There was a statistically significant difference between the groups, showing less estimated blood loss in the international unit group with a median of 80 mL (IQR, 60-100 mL) (P<0.001), and 200 mL (IQR, 143.75-300 mL) in the intramuscular (IM) group, highlighting that 66.8% of the IM group had an estimated blood loss >251 mL. ConclusionAny reduction in bleeding during labor is clinically relevant because it improves patient prognosis. The use of intraumbilical oxytocin injection with active management of the third stage of labor significantly reduced postpartum blood loss and the duration of the third stage compared with the IM group.

Genetic predisposition in NAFLD

( Silvia Sookoian ) 대한간학회 2016 간학회 싱글토픽 심포지움 Vol.2016 No.2

Precision medicine in nonalcoholic fatty liver disease: New therapeutic insights from genetics and systems biology

Silvia Sookoian,Carlos J. Pirola 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.4

Despite more than two decades of extensive research focusing on nonalcoholic fatty liver disease (NAFLD), no approved therapy for steatohepatitis—the severe histological form of the disease—presently exists. More importantly, new drugs and small molecules with diverse molecular targets on the pathways of hepatocyte injury, inflammation, and fibrosis cannot achieve the primary efficacy endpoints. Precision medicine can potentially overcome this issue, as it is founded on extensive knowledge of the druggable genome/proteome. Hence, this review summarizes significant trends and developments in precision medicine with a particular focus on new potential therapeutic discoveries modeled via systems biology approaches. In addition, we computed and simulated the potential utility of the NAFLD polygenic risk score, which could be conceptually very advantageous not only for early disease detection but also for implementing actionable measures. Incomplete knowledge of the druggable NAFLD genome severely impedes the drug discovery process and limits the likelihood of identifying robust and safe drug candidates. Thus, we close this article with some insights into emerging disciplines, such as chemical genetics, that may accelerate accurate identification of the druggable NAFLD genome/proteome.

The Role of Serine/Threonine Kinases in Signal Transduction : The Multi - gene Family of Protein Kinase C

Silvia Stable 한국유전학회 1990 Genes & Genomics Vol.12 No.4

Protein kinase C (PKC), originally identified as a novel cytoplasmic protein kinase, then recognized as the major phorbol ester receptor in mammalian cells is now defined as a family of at least seven related polypeptides encoded by separate genes and expressed in a tissue-specific manner (reviewed in: Stabel, 1990). This protein kinase has gained a central role in the analysis of signal transduction through numerous experiments providing evidence for activation of protein kinase C by the second messenger diacylglycerols produced mainly from the membrane lipids phosphatidylinositol and phosphatidylcholine. With the elucidation of the structural organization of the PKC molecule it became clear that the entity "PKC" comprises more than one polypeptide (Parker et al., 1986). The complexity of this enzyme family suggests that the individual members may serve distinct roles in signal transduction pathways. As an approach to analyse the characteristics of the PKC subtypes we have used the baculovirus - insect cell expression system to produce and isolate large amounts of the polypeptides encoded by the different genes (Patel and Stabel, 1989). The mammalian enzymes expressed in the insect cells are produced as phosphoproteins which show authentic protein kinase C properties and are amenable to biochemical characterization (Stabel et al., submitted). We have also used this expression system to express another serine/threonine kinase involved in signal transduction, the protooncogene product c-Raf, in order to analyse its activation and substrate requirements. Site-directed mutagenesis has proved a useful tool to dissect functional domains of polypeptides. The construction of a kinasenegative mutant of PKC type γ has allowed us to investigate the role of the kinase domain in post-translational modification of the PKC polypeptide and its role in defined events involving PKC. One such extensively studied event is the "downregulation" of PKC after prolonged phorbol ester treatment of mammalian cells, mainly fibroblasts, epithelial cells and hematopoietic cells, which mostly contain the α and/or β types of PKC (Kischel et al., 1990). We have introduced the PKC γ type which is exclusively expressed in nervous tissue into fibroblasts and shown that it is activated and downregulated by phorbol esters in vivo. The downregulation of the PKC-γ polypeptide by proteolytic degradation also proceeds if the molecule carries an inactivated kinase domain. This suggests that downregulation of PKC-γ is not a consequence of constitutive signalling through the kinase domain but rather due to an increased proteolytic susceptibility of the polypeptide after contact with phorbol esters (Freisewinkel et al., submitted). The kinase-deficient mutant is hypophosphorylated suggesting that a substantial proportion of the post-translational modification on PKC-γ is due to inter- or intramolecular autophosphorylation.

플랫폼 노동과 기간제 고용에 대한 개정 노동법의 배경과 주요 내용

Silvia Fernandez Martinez 한국노동연구원 2022 국제노동브리프 Vol.20 No.7

Orally Administered Multispecies Probiotic Formulations for the Modulation of the Gut-Skin-Brain Axis

Silvia Castegnaro 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

This work aims to provide the efficacy of two different multispecies probiotic formulations in modulating the gut-skin-brain axis through the promotion of skin relief and psychological wellbeing. Different trials were assessed to evaluate the improvement of skin conditions and stress-related situations after probiotic supplementations intake. To evaluate skin improvement with L. plantrum-PBS067, L. reuteri-PBS072 and L. rhamnosus-LRH020, two RDBPC clinical trial were done on 80 subjects for 8 weeks each, affected by atopic dermatitis or acne. Measured parameter were related to the condition: SCORAD, skin hydration, Trans Epidermal Water loss cytokine expression for atopic dermatitis and skin pH, sebum content, moisturization and clinical evaluation of acne lesions for acne. Instead, to assess the efficacy of another probiotic complex (L. reuteri-PBS072 and B. breve-BB077) in improving stress-related situations a proof of concept trial was ran on 30 stressed students for 28 days. Measured parameters: questionnaires to evaluate cognitive functions, sleep & anxiety and physiological markers collection. Then a crossover clinical trial to evaluate probiotics ability on mood and sleep during pandemic has been carried-out. A total of 33 volunteers were randomly assigned into two groups, A and B, with an inverted administration of probiotic supplement (4B CFU/day) and placebo for 30 days each, with a 4-week intermediate wash-out. The efficacy on stress response, in terms of mood and sleep behavior, were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Profile of Mood State (POMS) questionnaires. Globally, after 56 days of oral intake subjects showed a significant improvement of skin conditions presenting a beneficial effect only after 28 days of treatment. For atopic dermatitis results persist even after a month of wash-out. Clinically results on the students, demonstrate a significant improvement of short-term memory, attention and problem solving flexibility. Anxiety and sleep quality showed significant positive results together with a strong reduction of salivary cortisol and skin conductance. Results of the crossover clinical trial showed that both questionnaires reported a significant lower score after 30 days, while the placebo reported a higher score reflecting a worsening of mood and sleep quality. L. reuteri PBS072 and B. breve BB077 are potential probiotic candidates for improving stress resilience, cognitive functions and sleep quality. Another trial is on-going to determine probiotics action on post-partum women and their babies. Results demonstrated the ability of the actives in supporting the gut-brain-skin-axis manifestations providing the basis about the role of a daily probiotic supplementation for skin & brain health.

Arsenic Uptake and Partitioning in Grafted Tomato Plants

Silvia Rita Stazi,Carla Cassaniti,Rosita Marabottini,Francesco Giuffrida,Cherubino Leonardi 한국원예학회 2016 Horticulture, Environment, and Biotechnology Vol.57 No.3

Arsenic is a toxic and cancerogenic metalloid that poses a threat to food crop consumption. Previous studies have shown that grafting vegetables onto certain rootstocks may restrict the uptake of some toxic metals, such as cadmium, lead, and so on, but no such study has investigated the uptake of arsenic. The aim of this work was to determine the following: i) if grafting can influence and reduce arsenic translocation in the root and/or aerial organs; ii) how tomato plants irrigated with arsenic-enriched nutrient solution (100 μg·L-1) accumulate this metalloid; and iii) if arsenic poses a potential risk to fruit quality. We found that differences in plant growth and the qualitative traits of fruits were mainly related to the adopted rootstock rather than to the addition of arsenic. Grafting influenced metalloid accumulation in roots and its translocation from roots to shoots and fruits. Tomato plants accumulated arsenic in their roots, and only a small portion was translocated to shoots and fruits, making the risk for human consumption negligible. Therefore, the uptake of this toxic element and its translocation are influenced by the rootstock utilized.

Hesperidin Induces Non-Apoptotic Cell Death in Human HepG2 Cells

Silvia Yumnam,Gyeong Eun Hong,Suchismita Raha,Venu Venkatarame Gowda Saralamma,Ho Jeong Lee,Jeong Doo Heo,Sang Joon Lee,Gon Sup Kim 대한수의학회 2015 대한수의학회 학술대회발표집 Vol.2015 No.-

Global , Universal Human Rights in a Cross - Cultural Perspective

(Silvia Augeneder) 세계헌법학회 한국학회 2001 世界憲法硏究 Vol.6 No.-

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