РАЗРАБОТКА ТЕХНОЛОГИЧЕСКИХ ПАРАМЕТРОВ ДВУХСТАДИЙНОГО СПОСОБА ПОДГОТОВКИ СУШЕНОГО ТОПИНАМБУРА К ДИСТИЛЛЯЦИИ

For the production of distillates from Jerusalem artichoke, the technical and economic advantages of using dried raw materials are substantiated in comparison with the processing of fresh tubers, consisting in stabilizing the biochemical composition of raw materials and increasing its microbiological characteristics, eliminating seasonality, simplifying the technological process. The fractional composition of fructose containing carbohydrates of raw materials was studied and it was shown that in the process of obtaining dried Jerusalem artichoke, the main carbohydrates of raw materials depolymerize and, as a result, their accessibility to enzymatic hydrolysis is increased. The content of free reducing sugars (fraction FI) increases by 3–5 times, low molecular weight fraction of inulin (fraction FII) by 1.5 times. The albumin complex of dried Jerusalem artichoke is analyzed and it is established that the main protein fractions are albumins (58.2–61.5 % of total protein nitrogen), prolamines and glutelins are not found in the raw material. The factors influencing the technological parameters of the two-stage method for preparing dried artichoke for distillation are determined. At the first stage, when obtaining the sugared wort, a hydromodule (1 ÷ 4.5) was installed, the norm of the microbial inulinase task (3.0–4.5 units in/g inulin of the raw material), the duration of the enzymatic treatment (3 hours at a temperature of 52 ± 2 °С). Based on the study of the dynamics of CO2 emissions, the evaluation of the strength of fermented wort and the determination of volatile components in it, it is recommended to use dry alcoholic yeast Fermiol in the amount of 100 mg /100 g of wort, the process at a temperature of 28–30 °С, the fermentation time is 72 hours. it is shown that acidification of the medium in the wort preparation stage to pH 4.5 allows to reduce methanol content in the fermented wort.Для производства дистиллятов из топинамбура обоснованы технико-экономические преимущества использования сушеного сырья по сравнению с переработкой свежих клубней, заключающиеся в стабилизации биохимического состава сырья и повышении его микробиологических характеристик, исключении сезонности, упрощении технологического процесса. Исследован фракционный состав фруктозо-содержащих углеводов сырья и показано, что в процессе получения сушеного топинамбура происходит деполимеризация основных углеводов сырья и, как следствие, повышается степень их доступности к ферментативному гидролизу. Содержание свободных редуцирующих сахаров (фракция ФI) возрастает в 3–5 раз, низкомолекулярных фракция инулина (фракция ФII) в 1,5 раза. проанализирован белковый комплекс сушеного топинамбура и установлено, что основными фракциями белков являются альбумины (58,2–61,5% от общего белкового азота), в сырье не обнаружены проламины и глютелины. Определены факторы, влияющие на технологические параметры двухстадийного способа подготовки сушеного топинамбура к дистилляции. На первом этапе, при получении осахаренного сусла установлены гидромодуль (1÷4,5), норма задачи микробной инулиназы (3,0–4,5 ед. ИН/г инулина сырья), длительность ферментативной обработки (3 часа при температуре 52±2 °С). На основании изучения динамики выделения CO2, оценки крепости сброженного сусла и определения в нем летучих компонентов рекомендовано применение сухих спиртовых дрожжей Fermiol в количестве 100 мг/100 г сусла, проведение процесса при температуре 28–30 °С, длительность сбраживания — 72 часа. показано, что подкисление среды на стадии получения сусла до pH 4,5 позволяет снизить в сброженном сусле содержание метанола

Radiation Response of Cervical Cancer Stem Cells Is Associated with Pretreatment Proportion of These Cells and Physical Status of HPV DNA

Radio- and chemoresistance of cancer stem cells (CSCs) is considered as one of the possible causes of adverse results of chemoradiotherapy for various malignancies, including cervical cancer. However, little is known about quantitative changes in the CSC subpopulation in the course of treatment and mechanisms for individual response of CSCs to therapy. The purpose of the study was to evaluate the association of radiation response of cervical CSCs with clinical and morphological parameters of disease and features of human papillomavirus (HPV) infection. The proportion of CD44+CD24low CSCs was determined by flow cytometry in cervical scrapings from 55 patients with squamous cell carcinoma of uterine cervix before treatment and after fractionated irradiation at a total dose of 10 Gy. Real-time PCR assay was used to evaluate molecular parameters of HPV DNA. Post-radiation increase in the CSC proportion was found in 47.3% of patients. Clinical and morphological parameters (stage, status of lymph node involvement, and histological type) were not significantly correlated with radiation changes in the CSC proportion. Single- and multifactor analyses revealed two independent indicators affecting the radiation response of CSCs: initial proportion of CSCs and physical status of HPV DNA (R = 0.86, p = 0.001 for the multiple regression model in the whole)

Acidification in Distillation Technology

The quality of distillates depends on the biochemical composition of the raw material, the operating parameters of the wort production and fermentation, and the methods and modes of distillation. The active acidity of the medium (pH) can affect wort fermentation and distillation processes. The research objective was to study the effect of the active acidity of bakery waste wort on fermentation and distillation processes. The study featured fermented wort samples from wheat bread, a mix of wheat and rye-wheat bread, and distillate fractions obtained by a single fractionated distillation of fermented wort. The distillation occurred in laboratory conditions in a direct distillation unit (Kothe Destillationstechnik, Germany) with a 10 dm3 cube. The effect of the acidification degree of saccharified wort on the fermentation efficiency was determined by the strength of the fermented wort. The composition of volatile components in the distillates was defined by gas chromatography in a Thermo Trace GC Ultra chromatograph (Thermo, USA). When the pH of saccharified wort fell from 5.5 to 4.5–3.5, the synthesis of higher alcohols and ethers of higher fatty acids decreased during fermentation, while the acetone mass concentration increased. The acidification of fermented wort to pH = 3.5–3.0 at the distillation stage had a positive effect on the distillates from recyclable baking waste. This technique increased the yield of the middle fraction (distillate) by reducing the loss of absolute alcohol with the head and tail fractions. The concentration of acetaldehyde and ethyl acetate in the middle fraction decreased by 1.5 times while the content of enanthic ether components increased by more than 75%. As a result, the sensory profile increased by 0.4–0.5 points. The distillates from the mix of wheat and rye-wheat bread were superior to distillates from wheat bread. The statistical analysis provided the following criteria for a qualitative assessment of the distillates from recyclable baking waste: the mass concentration of acetaldehyde and the ratio of alcohols C5 to the sum of alcohols C3 and C4. Pre-fermentation oxidation of saccharified wort proved impractical for bakery waste recycling, whereas acidification of fermented wort before distillation increased the distillate yield and improved its sensory profile

Assessment-Based Optimization of Distillation Parameters

The range of high-quality alcoholic beverages could be expanded by unconventional raw materials, e.g., bakery waste. Any new technology requires optimization of operating parameters at each production stage. The sensory properties of an alcoholic drink depend on the distillation mode. However, food science knows no objective methods for optimizing distillation parameters based on the biochemical composition of the raw material. The research objective was to develop a new methodology for optimizing the distillation procedure for alcoholic drinks based on unconventional raw materials. The research featured distillates obtained from industrial samples of bakery waste. The variable factors included the distillation rate, which ranged from 5 to 17 cm3/min, and the wort acidification degree, which was pH 6.0–2.0. The composition and mass concentration of the main volatile components were determined by gas chromatography using a Thermo Trace GC Ultra device (Thermo, USA) with a flame ionization detector. The sensory evaluation was performed by a panel of qualified experts. The single-factor experiment showed that the distillation rate and the wort acidification degree affected the concentration of each volatile component in the distillate. Using the method of pairwise correlation coefficients, the authors identified the most significant parameters: mass concentration of 1-propanol, phenylethyl alcohol, ethyl lactate, total enanthic esters, total enanthic esters vs. total esters, concentration of ethyl lactate vs. total enanthic esters, isobutanol concentration vs.1-propanol concentration. The linear pair correlation coefficients were calculated for these selected indicators, and the effect of each parameter on the sensory profile was represented as a regression model. The optimal operating parameters were determined by extremization of a two-variable function: pH 4.4 ± 0.2, speed 9.5 ± 1.0 cm3/min. The new methodology provided for the following sequence of operations: determining the significance of the variable factor; selecting the evaluation parameters based on a single-factor experiment; determining the interaction; developing a regression model. This method can be used to calculate the optimal technological distillation parameters for other raw materials

Grain bran hydrolysates in the production of fruit distillates

Currently, there is an urgent need for domestic fermentation activators based on low-cost secondary raw materials. We aimed to study the effect of microbial enzyme preparations with different action on the hydrolysis of proteins and phytin of grain bran to obtain fermentation activators that could become an alternative to imported ones. We studied wheat and rye brans; microbial enzyme preparations with cytolytic, proteolytic, and phytase action; multi-enzyme compositions; and grain bran hydrolysates. Firstly, we determined the kinetic characteristics of enzyme preparations. Secondly, we evaluated their effectiveness in the hydrolysis of the brans. Thirdly, we developed multi-enzyme compositions. Finally, we determined the concentration of soluble forms of phosphorus and free amino acids in the hydrolysates. We determined optimal temperature and pH values for the enzyme preparations. The multi-enzyme compositions contributed to a high accumulation of reducing substances, water-soluble protein, and phosphorus. The concentration of free amino acids in the hydrolysates obtained under the action of the bran’s own enzymes was about 20% higher in the wheat samples, compared to the rye samples. However, when using multi-enzyme compositions in addition to the bran’s own enzymes, the concentration of free amino acids was 1.5 times higher in the rye hydrolysates, compared to the wheat hydrolysates. The use of multi-enzyme compositions under optimal conditions can double the content of phosphorus and free amino acids available for yeast, compared to the control. Our results can be used for further research into using grain bran hydrolysates as an alternative source of nitrogen and phosphorus nutrition for yeast at the fermentation stage of fruit distillate production

Association of the Apolipoprotein E 2 Allele with Concurrent Occurrence of Endometrial Hyperplasia and Endometrial Carcinoma

Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH) and endometrial carcinoma (ECa). Patients with EH (n = 89), EH concurrent with ECa (n = 76), ECa (n = 186), and healthy controls (n = 1110) were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOE Cys112Arg and Arg158Cys), iron (HFE Cys282Tyr and His63Asp), and catecholamines (COMT Val158Met). Patients and controls were matched by ethnicity (all Caucasians), age, body mass index (BMI), and incidence of hypertension and diabetes. The frequency of the APOE E 2 allele (158Cys) was higher in patients with EH + ECa than in controls (P = 0.0012, PBonferroni = 0.018, OR = 2.58, 95% CI 1.49–4.45). The APOE E 4 allele (112Arg) was more frequently found in patients with EH than in controls and HFE minor allele G (63Asp) had a protective effect in the ECa group, though these results appeared to be nonsignificant after correction for multiple comparisons. The results of the study indicate that E 2 allele might be associated with concurrent occurrence of EH and ECa

Prognostic Value of Serum Transferrin Analysis in Patients with Ovarian Cancer and Cancer-Related Functional Iron Deficiency: A Retrospective Case–Control Study

(1) Background: There are no reliable and widely available markers of functional iron deficiency (FID) in cancer. The aim of the study was to evaluate the role of transferrin (Tf) as a marker of cancer of the ovary (CrO) and related FID. (2) Methods: The study groups consisted of 118 patients with CrO and 69 control females. Blood serum iron status was determined on a Beckman Coulter AU (USA) analyzer. Tf quantification was performed by immunoturbidimetry. The relative contents of apo- and holo-Tf (iron-free and iron-saturated Tf, respectively) were determined in eight patients and a control female by immunochromatographic analysis based on the use of monoclonal single-domain antibodies (nanobodies). (3) Results: Four groups of patients with different iron statuses were selected according to ferritin and transferrin saturation values: absolute iron deficiency (AID) (n = 42), FID (n = 70), iron overload (n = 4), normal iron status (n = 2). The groups differed significantly in Tf values (p < 0.0001). Lower values of Tf were associated with FID. Furthermore, FID is already found in the initial stages of CrO (26%). Immunosorbents based on nanobodies revealed the accumulation of apo-Tf and the decrease in holo-Tf in patients with CrO. (4) Conclusions: Tf may be a promising tool for diagnosing both CrO and associated FID

Prognostic Value of Serum Transferrin Analysis in Patients with Ovarian Cancer and Cancer-Related Functional Iron Deficiency: A Retrospective Case–Control Study

(1) Background: There are no reliable and widely available markers of functional iron deficiency (FID) in cancer. The aim of the study was to evaluate the role of transferrin (Tf) as a marker of cancer of the ovary (CrO) and related FID. (2) Methods: The study groups consisted of 118 patients with CrO and 69 control females. Blood serum iron status was determined on a Beckman Coulter AU (USA) analyzer. Tf quantification was performed by immunoturbidimetry. The relative contents of apo- and holo-Tf (iron-free and iron-saturated Tf, respectively) were determined in eight patients and a control female by immunochromatographic analysis based on the use of monoclonal single-domain antibodies (nanobodies). (3) Results: Four groups of patients with different iron statuses were selected according to ferritin and transferrin saturation values: absolute iron deficiency (AID) (n = 42), FID (n = 70), iron overload (n = 4), normal iron status (n = 2). The groups differed significantly in Tf values (p < 0.0001). Lower values of Tf were associated with FID. Furthermore, FID is already found in the initial stages of CrO (26%). Immunosorbents based on nanobodies revealed the accumulation of apo-Tf and the decrease in holo-Tf in patients with CrO. (4) Conclusions: Tf may be a promising tool for diagnosing both CrO and associated FID

Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial

Background: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. Methods: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres)in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO)stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1)using a permuted block method (block size of six patients)to receive six cycles of paclitaxel (175 mg/m2)and carboplatin (area under the serum concentration-time curve 5 or 6)every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. Findings: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7–34·2), 626 patients had progression-free survival events (405 [60%]of 678 in the trebananib group and 221 [66%]of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0–17·6])and the placebo group (15·0 months [12·6–16·1])groups (hazard ratio 0·93 [95% CI 0·79–1·09]; p=0·36). 512 (76%)of 675 patients in the trebananib group and 237 (71%)of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%]vs placebo 126 [38%])anaemia (76 [11%]vs 40 [12%]), and leucopenia (81 [12%]vs 35 [10%]). 269 (40%)patients in the trebananib group and 104 (31%)in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. Interpretation: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. Funding: Amgen

Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial

Background Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial.Methods TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m(2)) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for u p to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses induded patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials. gov , number NCT01493505, and is complete.Findings Between Jan 30,2012, and Feb 25,2014,1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27.4 months (IQR 17.7-34.2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15.9 months [15.0-17.6]) and the placebo group (15.0 months [12.6-16.1]) groups (hazard ratio 0.93 [95% CI 0.79-1.09]; p=0.36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] vs placebo 126 [38%]) anaemia (76 [11%] vs 40 [12%]), and leucopenia (81 [12%] vs 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group.Interpretation Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. Copyright (C) 2019 Elsevier Ltd. All rights reserved.Experimentele farmacotherapi