Comparative study of biocorrective protein-peptide agent to improve quality and safety of livestock products

Water with modified isotopic composition (D/H = 40 ppm) as a solubilizing agent for biologically active substances extraction from immune organs Sus Scrofa increases protein yield in thymus to 20%, in spleen up to 38%, mesenteric lymph nodes up to 35% in comparison with distilled water (D/H = 150 ppm). It was found a significant amount of neurotransmitter amino acids, such as aspartic and glutamic acids, glycine (thymus - 10.5; 13.7; 7.6%; spleen - 12.2; 10.7; 7.8% lymph nodes - 11.0; 13.3; 11.1%, respectively) having the immunological and adaptogenic activity, in extracts of Sus scrofa immunocompetent organs (thymus, spleen, mesenteric lymph nodes). Application of water with modified isotopic composition as solubilizing agent (D / H = 40 ppm) for extraction of immunocompetent organs' biologically active compounds led to increased amino acid content, including hydrophilic amino acids, in thymus extracts - up to 22%, in spleen extracts - up to 15% , in lymph nodes exctracts - up to 8%, in comparison to distilled water (D / H = 150 ppm). Peptide profile analysis revealed positive effect of water (D/H = 40 ppm) on a quality protein content extracts in molecular weight range from 10 to 20 kDa and from 30 to 45 kDa and peptide composition (2 kDa), at the same time quantitative content of compounds adaptogenic and immunocorrective action increased. Reducing of deuterium content in the solubilizing agent enhances quantitative amino acid content, i.e. extraction in an aqueous- salt solution based on deuterium depleted water of animal tissues with a high content of amino acids with hydrophilic radicals proceeded more completely

Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer

The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death. These observations were reflected in assessment of human disease, indicating the clinical relevance of the AR/E2F1 cooperome in prostate cancer. Together, these studies reveal new mechanisms by which RB loss induces cancer progression and highlight the importance of understanding the targets of E2F1 function. SIGNIFICANCE: This study identifies that RB loss in prostate cancer drives cooperation between AR and E2F1 as coregulators of transcription, which is linked to the progression of advanced disease

The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair.

Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of DNA repair. Key findings demonstrate that CRY1 expression is androgen-responsive and associates with poor outcome in prostate cancer. Functional studies and first-in-field mapping of the CRY1 cistrome and transcriptome reveal that CRY1 regulates DNA repair and the G2/M transition. DNA damage stabilizes CRY1 in cancer (in vitro, in vivo, and human tumors ex vivo), which proves critical for efficient DNA repair. Further mechanistic investigation shows that stabilized CRY1 temporally regulates expression of genes required for homologous recombination. Collectively, these findings reveal that CRY1 is hormone-induced in tumors, is further stabilized by genomic insult, and promotes DNA repair and cell survival through temporal transcriptional regulation. These studies identify the circadian factor CRY1 as pro-tumorigenic and nominate CRY1 as a new therapeutic target

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

Effects of tissue-specific biomolecules on piglets after-weaning period

Background and Aim: Now-a-days antibiotics are the main tool for correcting the pathological conditions of pigs; unfortunately, antibiotics are a potential threat to the environment, as they lead to the spread of antibiotic-resistant infections. This study aimed to study the immunomodulatory encapsulated biomolecules on piglets in the post-weaning period. Materials and Methods: An immunomodulator based on biomolecules obtained from animal raw materials included in alginate capsules to improve absorption has been developed. The study presents the results of a study on 25 weaned piglets (25-30 days old) which received biomolecules at a dose of 200 mg/piglet for 14 days, followed by 400 mg/piglet from days 15 to 28. Blood was taken from animals for analysis (biochemical, hematological, cytometric, and enzyme immunoassay) and the integral index of blood serum antimicrobial activity was determined. Results: Experimental animals, whose initial weight was 1.6 times less than that of the control animals, were able to bridge this gap and, on the 28th day, there were no differences in weight. Stimulation of the production of cytokines interleukin (IL)-2 and IL-4 was observed and the antimicrobial resistance of blood serum to Escherichia coli also increased. A positive effect on the metabolism of piglets was noted, which helped them adapt to a change in diet (from colostrum to solid food). Conclusion: The results show that the immunomodulation at the dose of 150 mg/kg body weight has a great potential for improving weaned pigs