Knigth's Move in the Periodic Table, From Copper to Platinum, Novel Antitumor Mixed Chelate Copper Compounds, Casiopeinas, Evaluated by an in Vitro Human and Murine Cancer Cell Line Panel

We synthesized a novel anticancer agents based on mixed chelate copper (II) complexes, named Casiopeínas® has of general formula [Cu(N-N)(N-O)H2O]NO3 (where, N-N = diimines as 1,10- phenanthroline, 2,2-bipyridine, or substituted and N-O=aminoeidate or [Cu(N-N)(O-O)H2O]NO3 (where NN= diimines as 10-phenanthroline, 2,2-bipyridine or substituted Casiopeínas I, II, IV, V, VI, VII VIII and O-O=acetylacetonate, salicylaldehidate Casiopínas III). We evaluated the in vitro antitumor activity using a human cancer cell panel and some nurine cancer cells. Eleven Casiopeinas are evaluated in order to acquire some structure-activity correlations and some monodentated Casiopeinäs analogues; cisplatinum was used as control drug. The 50% growth inhibition observed is, in all cases reach with concentrations of Casiopeina's 10 or 100 times lower than cisplatinum. In a previous work we reported the induction of apoptosis by Casiopeina II. The results indicate that Casiopeinass are a promising new anticancer drug candidates to be developed further toward clinical trials

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Functional Effects of Prebiotic Fructans in Colon Cancer and Calcium Metabolism in Animal Models

Inulin-type fructans are polymers of fructose molecules and are known for their capacity to enhance absorption of calcium and magnesium, to modulate gut microbiota and energy metabolism, and to improve glycemia. We evaluated and compared the effects of Chicory inulin “Synergy 1®” and inulin from Mexican agave “Metlin®” in two experimental models of colon cancer and bone calcium metabolism in mice and rats. Inulins inhibited the development of dextran sulfate sodium-induced colitis and colon cancer in mice; these fructans reduced the concentration of tumor necrosis factor alpha and prevented the formation of intestinal polyps, villous atrophy, and lymphoid hyperplasia. On the other hand, inulin treatments significantly increased bone densitometry (femur and vertebra) in ovariectomized rats without altering the concentration of many serum biochemical parameters and urinary parameters. Histopathology results were compared between different experimental groups. There were no apparent histological changes in rats treated with inulins and a mixture of inulins-isoflavones. Our results showed that inulin-type fructans have health-promoting properties related to enhanced calcium absorption, potential anticancer properties, and anti-inflammatory effects. The use of inulin as a prebiotic can improve health and prevent development of chronic diseases such as cancer and osteoporosis

Stevia rebaudiana Bertoni, an American plant used as sweetener: Study of its effects on body mass control and glycemia reduction in Wistar male and female rats.

Stevia rebaudiana Bertoni water extracts have been used as a natural sweetener and customary medicine by the indigenous inhabitants of South America for several hundred years. This plant was sent to Europe in the 16th century and was described by Peter Jacob Esteve in Spain. Recently the food industry has started to employ S. rebaudiana as sweetener using its glycosides after purification. Advertisement claims that Stevia glycosides is good for controling body mass and reducing glycemia. This study's objective was to evaluate the effect of S. rebaudiana leaf extract on Wistar rats as animal model to prove its effectiveness on body mass control, glycemia reduction, and other biochemical parameters. Three groups were randomly formed with 24 males and 24 females: A blank group without any sweetener, a control group drinking water with 10% glucose, and the test group ingesting a 0.94% water extract of S. rebaudiana. Body mass measurements as well as food and drink consumption were daily performed. The experiment lasted 120 days after the specimens were weaned and got used to eating solid food. Euthanasia was done and blood serum was collected to evaluate the following biochemical parameters: Glucose, triglycerides, cholesterol, insulin, glucagon, leptin, ghrelin, and glucose-dependent insulinotropic peptide, GIP. Results indicated that only female rats had statistical differences in body mass gain. No relevant effects either positive or negative were found in the biochemical parameters measured. The crude extracts of S. rebaudiana did not show any relevant changes in biochemical and hormonal profiles, changes nor body mass with respect to the blank and control groups of young and healthy rats in the age range of infancy to youth. According to the results obtained, the therapeutic properties that have been associated to S. rebaudiana consumption especially for body mass control and glycemia reduction, did not occur in young and healthy male and female rats in equivalent age to infants, young children, and youths

Fig 3 -

A. Male Wistar rats daily food intake during 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Each line represents the trend in the evaluated period where each point comprises the average food intake of each group and its CI at 95%, n = 8. B. Female Wistar rats daily food intake during 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Each line represents the trend in the evaluated period where each point comprises the average food intake of each group and its CI at 95%, n = 8. C. Male Wistar rats statistical analyses of final cumulative food intake data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). The following letters indicate significant differences p<0.05: a, b, c, d. Duncan test. D. Female Wistar rats statistical analyses of final cumulative food intake data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). The following letters indicate significant differences p<0.05: a, b, c, d. Duncan test.</p

Methodology for preparing infusions and quantification of glucosides of interest (modified of [34]).

Methodology for preparing infusions and quantification of glucosides of interest (modified of [34]).</p

Fig 7 -

A. Male Wistar rats statistical analyses of serum insulin data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. B. Female Wistar rats statistical analyses of serum insulin data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. C. Male Wistar rats statistical analyses of serum glucagon data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. D. Female Wistar rats statistical analyses of serum glucagon data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. E. Male Wistar rats statistical analyses of serum leptin data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. F. Female Wistar rats statistical analyses of serum leptin data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. G. Male Wistar rats statistical analyses of serum ghrelin data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. H. Female Wistar rats statistical analyses of serum ghrelin data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. I. Male Wistar rats statistical analyses of serum glucose dependent insulinotropic peptide, GIP, data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. J. Female Wistar rats statistical analyses of serum glucose dependent insulinotropic peptide, GIP, data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8.</p

S1 Raw data -

Stevia rebaudiana Bertoni water extracts have been used as a natural sweetener and customary medicine by the indigenous inhabitants of South America for several hundred years. This plant was sent to Europe in the 16th century and was described by Peter Jacob Esteve in Spain. Recently the food industry has started to employ S. rebaudiana as sweetener using its glycosides after purification. Advertisement claims that Stevia glycosides is good for controling body mass and reducing glycemia. This study’s objective was to evaluate the effect of S. rebaudiana leaf extract on Wistar rats as animal model to prove its effectiveness on body mass control, glycemia reduction, and other biochemical parameters. Three groups were randomly formed with 24 males and 24 females: A blank group without any sweetener, a control group drinking water with 10% glucose, and the test group ingesting a 0.94% water extract of S. rebaudiana. Body mass measurements as well as food and drink consumption were daily performed. The experiment lasted 120 days after the specimens were weaned and got used to eating solid food. Euthanasia was done and blood serum was collected to evaluate the following biochemical parameters: Glucose, triglycerides, cholesterol, insulin, glucagon, leptin, ghrelin, and glucose-dependent insulinotropic peptide, GIP. Results indicated that only female rats had statistical differences in body mass gain. No relevant effects either positive or negative were found in the biochemical parameters measured. The crude extracts of S. rebaudiana did not show any relevant changes in biochemical and hormonal profiles, changes nor body mass with respect to the blank and control groups of young and healthy rats in the age range of infancy to youth. According to the results obtained, the therapeutic properties that have been associated to S. rebaudiana consumption especially for body mass control and glycemia reduction, did not occur in young and healthy male and female rats in equivalent age to infants, young children, and youths.</div

Fig 5 -

A. Male Wistar rats statistical analyses of theoretically calculated energy cumulative intake data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Duncan test. B. Female Wistar rats statistical analyses of theoretically calculated energy cumulative intake data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Duncan test.</p

Fig 6 -

A. Male Wistar rats statistical analyses of blood serum glucose data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. B. Female Wistar rats statistical analyses of blood serum glucose data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. C. Male Wistar rats statistical analyses of serum triglycerides data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. D. Female Wistar rats statistical analyses of serum triglycerides data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. E. Male Wistar rats statistical analyses of serum cholesterol data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8. F. Female Wistar rats statistical analyses of serum cholesterol data 120 days after weaning consuming stevia infusion, drinking water sweetened with glucose (control), and plain water (blank). Its CI is at 95%. The following letters indicate significant differences p<0.05: a, b, c, d. Games-Howell Method n = 8.</p