Antitumor activity of Bulgarian herb Tribulus terrestris L. on human breast cancer cells

Medicinal plants have been intensively studied as a source of antitumor compounds. Due to the beneficial climate conditions Bulgarian herbs have high pharmacological potential. Currently, the antitumor effect of the Bulgarian medicinal plant Tribulus terrestris L. on human cancer cell lines is not studied. The main active compounds of the plant are the steroid saponins.The present study aims to analyze the effect on cell viability and apoptotic activity of total extract and saponin fraction of Bulgarian Tribulus terrestris L. on human breast cancer (MCF7) and normal (MCF10A) cell lines. Antitumor effect was established by МТТ cell viability assay and assessment of apoptotic potential was done through analysis of genomic integrity (DNA fragmentation assay) and analysis of morphological cell changes (Fluorescence microscopy). The results showed that total extract of the herb has a marked dose-dependent inhibitory effect on viability of MCF7 cells (half maximal inhibitory concentration is 15 μg/ml). Cell viability of MCF10A was moderately decreased without visible dose-dependent effect. The saponin fraction has increased inhibitory effect on breast cancer cells compared to total extract. Morphological changes and DNA fragmentation were observed as markers for early and late apoptosis predominantly in tumor cells after treatment. Apoptotic processes were intensified with the increase of treatment duration.The obtained results are the first showing selective antitumor activity of Bulgarian Tribulus terrestris L. on human cancer cells in vitro. Apoptotic processes are involved in the antitumor mechanisms induced by the herb. This results give directions for future investigations concerning detailed assessment of its pharmacological potential

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Ultrasonic Synthesis and Preliminary Evaluation of Anticoronaviral Activity of 6,7-Dimethoxy-4-(4-(4-methoxyphenyl)piperazin-1-yl)-1-methylquinolin-1-ium Iodide

Quinoline scaffold is one of the most intensively utilized pharmacophores in drug design because of the variety of activities demonstrated by different quinoline-based therapeutics or drug-candidates. Herein, we describe an environmentally tolerant two-step procedure as a convenient synthetic approach to novel chloroquine and hydroxychloroquine analogues. The structures of the newly synthesized compounds are estimated by 1H NMR, 13C NMR, LC-MS spectrometry and IR spectroscopy

Ultrasonic Synthesis and Preliminary Evaluation of Anticoronaviral Activity of 6,7-Dimethoxy-4-(4-(4-methoxyphenyl)piperazin-1-yl)-1-methylquinolin-1-ium Iodide

Quinoline scaffold is one of the most intensively utilized pharmacophores in drug design because of the variety of activities demonstrated by different quinoline-based therapeutics or drug-candidates. Herein, we describe an environmentally tolerant two-step procedure as a convenient synthetic approach to novel chloroquine and hydroxychloroquine analogues. The structures of the newly synthesized compounds are estimated by 1H NMR, 13C NMR, LC-MS spectrometry and IR spectroscopy

Microbial diversity and health-promoting properties of the traditional Bulgarian yogurt

Bulgarian yogurt is usually associated with good health and longevity. This study aimed to analyse the current microbial content of homemade Bulgarian yogurt. Identification by 16S rDNA sequencing revealed that out of 76 isolated strains, 53% belonged to Lactobacillus delbrueckii subsp. bulgaricus, 14% to other lactobacilli, and 32% to lactic acid cocci (Streptococcus thermophilus, Pediococcus acidilactici, Enterococcus faecium and Leuconostoc). All isolates inhibited the growth of pathogenic bacteria (10% of them by the putative action of bacteriocins); 18 isolates were able to produce extracellular exopolysaccharides (EPS), whereas 24% of them demonstrated extremely high proteolytic activity. Remarkably, 10 Lb. bulgaricus strains produced prebiotic galactooligosaccharides (GOS). High-resolution accurate mass spectrometry (HRAMS) analysis revealed production of tri- and tetrasaccharides containing atypical β(1→4) glycosidic bonds, reported for the first time for Lb. bulgaricus. Based on the beneficial features, along with good technological behaviour, we recommend several isolates as highly promising for Bulgarian yogurt starters

Serum anti-α-crystallin antibodies in women with endocrine disorders

There is a distinct group among the patients with unexplained infertility who are found to have enhanced humoral immune response. Recent studies focus on the expression of stress proteins being an important factor in the stages of gametogenesis, fertilization, implantation, early embryonic development and pregnancy. Increased expression of stress proteins and immune response against them was found in tissues exposed to stress. There is not enough data linking infertility to expression and immunity of α-crystallins in patients with endocrine diseases. The aim of this work was to study anti-α-crystallin antibodies in patients with polycystic ovary syndrome (PCOS), Graves’ disease, autoimmune thyroiditis, diabetes mellitus and obesity. Sera samples from 169 women with endocrine disorders (PCOS (n = 68); Graves’ disease (n = 26); autoimmune thyroiditis (n = 32); diabetes mellitus (n = 10); and obesity (n = 33)) were tested by ELISA. The statistical analysis was performed using SPSS program. The concentration of anti-α-crystallin antibodies is significantly elevated in the PCOS group compared to the control group (p = 0.021). The frequency of positive sera in the same group of patients is significantly higher compared to the control group (p = 0.029). In all other groups, no statistically significant elevation was observed. Elevated concentrations of anti-α-crystallin antibodies found in patients with PCOS suggest that the increased production of anti-α-crystallin antibodies in women with PCOS is most probably caused by failure of the immune tolerance and the induction of immune response. This is most likely due to an increased expression of this stress protein as a result of oxidative stress and chronic inflammation

Solution structure of the major alpha-amylase inhibitor of the crop plant amaranth.

alpha-Amylase inhibitor (AAI), a 32-residue miniprotein from the Mexican crop plant amaranth (Amaranthus hypochondriacus), is the smallest known alpha-amylase inhibitor and is specific for insect alpha-amylases (Chagolla-Lopez, A., Blanco-Labra, A., Patthy, A., Sanchez, R., and Pongor, S. (1994) J. Biol. Chem. 269, 23675-23680). Its disulfide topology was confirmed by Edman degradation, and its three-dimensional solution structure was determined by two-dimensional 1H NMR spectroscopy at 500 MHz. Structural constraints (consisting of 348 nuclear Overhauser effect interproton distances, 8 backbone dihedral constraints, and 9 disulfide distance constraints) were used as an input to the X-PLOR program for simulated annealing and energy minimization calculations. The final set of 10 structures had a mean pairwise root mean square deviation of 0.32 A for the backbone atoms and 1.04 A for all heavy atoms. The structure of AAI consists of a short triple-stranded beta-sheet stabilized by three disulfide bonds, forming a typical knottin or inhibitor cystine knot fold found in miniproteins, which binds various macromolecular ligands. When the first intercystine segment of AAI (sequence IPKWNR) was inserted into a homologous position of the spider toxin Huwentoxin I, the resulting chimera showed a significant inhibitory activity, suggesting that this segment takes part in enzyme binding