Search

Foreign food industries know a variety of products derived from wine yeast cells. These products are used to improve the sensory properties of wine. This article describes the effect of a new yeast biosorbent on the sensory and physicochemical properties of white and red wine, e.g., their sorption capacity for heavy metals. The research featured red and white wines treated with the novel biosorbent. Glutarom (France) served as control. The study relied on various physicochemical, organoleptic, biochemical, and microbiological methods. The biosorbent affected neither the volume fraction of ethyl alcohol nor the mass concentration of sugars and titrated acids. However, the biosorbent reduced the mass concentration of volatile acids in terms of acetic acid: it decreased by 20% in the white wines and by 50% in the red wine samples. The mass concentration of the reduced extract decreased by 0.2–0.7 g/dm3 as the amount of sorbent increased. In the white wine samples, the protein concentration decreased by 1.5–1.8 times, while the concentration of polysaccharides decreased by 110–115 mg/dm3. The content of phenolic compounds decreased by 13–37%, depending on the amount of the sorbent, due to their condensed forms. The biosorbent reduced the value of the redox potential. The yeast sorbents effectively adsorbed metal cations, including those of heavy metals. A set of experiments also revealed the difference in sorption time for different metal cations. The effectiveness of the biosorbent was dose-dependent. The wines treated with the biosorbent had better sensory assessment results, especially the red wine samples. They had a soft, round, and harmonious flavor and a bright aroma with pronounced varietal tones. The novel biosorbent proved to have a good sorption capacity for phenolic compounds, as well as cations of toxic metals. It improved the sensory profile of the red and white wines. This biosorbent can substitute their imported analogs in the Russian wine industry.

Introduction. The concentration of biogenic amines is an important indicator of the safety of food products, especially winemaking. In grape wines, this concentration varies widely depending on the grape variety, its microbiological state, processing technology, the race of yeast and bacteria of malolactic fermentation, conditions of alcoholic and malolactic fermentation, etc. This research is aimed at determining the effect of the production technology of dry white and red wines on the concentration of biogenic amines. Study objects and methods. The mass concentration of biogenic amines was determined by the method of high-performance capillary electrophoresis using a Kapel 105R in laboratory-obtained samples of dry white wine from the Chardonnay grape variety and table dry red wine from the Cabernet-Sauvignon grape variety. Results and discussion. The dry white wine samples revealed high concentrations of tyramine (1.12 mg/dm³), phenylethydamine (0.58 mg/dm³), and histamine (0.57 mg/dm³), while the red wine samples demonstrated tyramine (0.62 mg/dm³), histamine (0.45 mg/dm³), putrescine (0.43 mg/dm³), and cadaverine (0.38 mg/dm³). The white wine samples had optimal pH values (3.2–3.6) with minimal formation of biogenic amines. The red wine samples, especially those obtained by heat treatment, had a lower concentration of biogenic amines, especially volatile biogenic amines, i.e. methylamine and phenylethylamine. The greatest formation of biogenic amines occurred during the acid reduction process: under the effect of enzymes of malolactic bacteria, biogenic amines formed as a result of decarboxylation of amino acids. Conclusion. The technology of production of table dry white and red wines affects the concentration of biogenic amines. To reduce the level of biogenic amines in the finished product, each stage of vinification has to be controlled, especially the stages of fermentation and acid reduction (temperature and pH). The race of yeast and lactic acid bacteria cannot include those that produce biogenic amines or introduce them in minimal quantities.

Outcomes for patients with acute myeloid leukemia (AML) remain poor due to the inability of current therapies to fully eradicate disease initiating leukemia stem cells (LSCs) (Shlush et al., 2017). Many studies have demonstrated that LSCs have unique metabolic properties compared to AML blasts (Jones et al., 2021). However, the metabolite profiles of human LSCs and hematopoietic stem and progenitor cells (HSPCs) have not yet been directly compared. To examine metabolite levels in enriched LSCs and HSPCs we used mass spectrometry-based metabolomics analysis on enriched LSCs from 18 AML patients and HSPCs from 9 normal bone marrow (BM) specimens. Pathway analysis showed that arginine metabolism and biosynthesis were the most significantly enriched pathways in LSCs compared to HSPCs. Clinical studies have shown limited efficacy of targeting arginine levels using arginine degrading enzymes; therefore, we sought to target pathways downstream of arginine. Stable isotope labeled tracing analysis showed arginine was metabolized through the urea cycle into polyamines in human LSCs. Polyamines are cationic compounds which have been previously shown to be important for the growth of various cancers but their role in AML LSCs has yet to be determined. To investigate if polyamines are essential for LSC survival and function, we treated LSCs and HSPCs with N1,N11-diethylnorspermine (DENSpm), a polyamine analog causing polyamine depletion through increased cellular export. DENSpm treatment decreased the viability of LSCs and AML blasts in 10 out of 12 of patients tested but had no impact on HSPC viability. Further, treatment with DENSpm resulted in decreased engraftment potential of the 4 AML specimens examined in immune deficient mice but did not alter the engraftment of normal HSPCs, suggesting that targeting polyamines represents a promising approach to kill LSCs while sparing HSPCs. We then investigated the mechanisms regulated by polyamines in LSCs. Using RNA-sequencing analysis on enriched LSCs from 5 AML patients and HSPCs from 3 normal BM specimens we observed decreased expression of genes involved in protein synthesis in DENSpm-treated LSCs but not normal HSPCs. Protein synthesis and its regulation are critical for AML survival (Chen et al., 2019; Messling et al., 2022) but the role of polyamines in protein translation in LSCs has not been explored. Polyamines stimulate translation notably by serving as precursors for the hypusination of eukaryotic translation initiation factor 5A (eIF5A) (Park et al., 2010). Accordingly, DENSpm led to reduced protein synthesis level in MOLM13 AML cell line and primary AML samples. Strikingly, protein synthesis and viability were rescued upon co-treatment with spermidine, suggesting that DENSpm induces AML cells death at least in part through decreased eIF5A-mediated protein translation. Altogether, our data demonstrates that depletion of polyamines decreased LSC function while sparing normal HSPCs. Mechanistically, our data suggest that LSC targeting is accomplished through polyamine regulated protein synthesis. Citation Format: Vincent Rondeau, Cristiana O’Brien, Jacob M Berman, Duhan Yendi, Tianyi Ling, Aleksandra Bourdine, Aarushi Gupta, Jonathan St-Germain, Rachel Culp-Hill, Julie A Reisz, Soheil Jahangiri-Tazehkand, Anastasia Tikhonova, Andrea Arruda, Mark D Minden, Angelo D’Alessandro, Brian Raught, Courtney L Jones. Polyamines are required for AML LSC function through their role in regulating eIF5A dependent protein synthesis [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A54.

T-cell acute lymphoblastic leukemia (T-ALL) represents a particularly aggressive subtype of leukemia with no targeted therapies or immune interventions. Currently, in response to intensive chemotherapy, ~25% of pediatric and 50% of adult patients undergo relapse and succumb to this therapy-resistant disease. Patients that relapse have poor outcomes, with Citation Format: Mark Gower, Minerva Fernandez, Andrea Aruda, Mark Minden, Johann Hitzler, Anastasia Tikhonova. Dissecting immune microenvironment of T-cell acute lymphoblastic leukemia. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr NG14.

Acute myeloid leukemia (AML) is a devastating hematologic malignancy diagnosed in over 20,000 patients each year in the United States. The five-year survival rate in adult AML is less than 30%, highlighting the need for novel therapies to treat this malignancy. Current therapeutic approaches fail in part due of their inability to fully eradicate the disease-initiating leukemia stem cells (LSCs). Our previous work and the work of many others has demonstrated that LSCs have unique metabolic dependencies compared to the more differentiated AML blasts population. Importantly, these metabolic differences can be targeted to specifically eradicate the LSC population. To date, limited studies have examined the difference in metabolism between human LSCs and their normal counterparts, hematopoietic stem cells (HSCs), at the level of individual metabolites. To address this gap in our knowledge, we performed an unbiased mass spectrometry-based metabolomics analysis hematopoietic stem and progenitor cells (HSPCs) enriched from the bone marrow of 7 healthy donors and LSCs enriched from 18 primary AML patient specimens. This analysis revealed 38 metabolites that were significantly different between LSCs and HSPCs (FDR Citation Format: Vincent Rondeau, Rachel Culp-Hill, Cristiana O’Brien, Jacob Berman, Julie A. Reisz, Duhan Yendi, Tianyi Ling, Soheil Janangiri, Anastasia Tikhonova, Angelo D’Alessandro, Courtney Jones. Targeting polyamines metabolism in acute myeloid leukemia stem cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr NG07.

Experimental data on the content of biologically valuable components in grape pomace are presented. The presence of organic acids was revealed in an amount from 33.35 g/kg (Saperavi) to 108.2 g/kg (Rebo). The main acid is tartaric. Phenolic compounds have been identified: anthocyanins, flavones, flavan-3-ols, oxycinnamic and hydroxybenzoic acids, procyanidins. The main anthocyanins found in grape pomace are the 3-O-glycosides of malvidin, petunidin, cyanidin, peonidin and delphinidin. The highest total content of hydroxybenzoic acids was in the pomace of Pinot Noir grapes – 720 mg/kg, further in descending order of concentration followed by pomace from Saperavi grapes (708 mg/kg), Cabernet Sauvignon (681 mg/kg), Merlot (575 mg/kg) and Rebo (545 mg/kg). The highest total content of vitamins was found in the pomace of Rebo grapes – 639 mg/kg, the lowest – Merlot (471 mg/kg). In all samples, vitamin B1 prevails, then in decreasing order – ascorbic acid, vitamins B2, B3, B5, B7. Moreover, their concentrations vary significantly depending on the grape variety from which the pomace is obtained. The influence of the grape variety on the content of these biologically valuable components in the pomace has been established, which must be taken into account in the production of biologically active substances that increase the nutritional status of a person.

The article is devoted to the research of the makeup of phenolic compounds and fatty acids of grape pomace. The phenolic compounds were identified in skin and seed extracts and in extracts of skin-and-seed mixtures; the fatty acids – in grape oil generated by direct pressing. It was established that anthocyanins were present mainly in the skins. Low concentrations of ten components of the anthocyanin complex were identified in the Saperavi seeds. Maximum amounts of anthocyanins were found in the Saperavi skins. The concentration of quercetin distinguished by a PP-vitamin activity was by 1.5 to 2.0 times higher in the skin-andseed mixtures, especially of Roesler grapes, than in the skin itself. Maximum amounts of flavan-3-ols, hydroxy-cinnamic and hydroxybenzoic acids and oligomeric procyanidins, as well as the highest antioxidant activity were observed in the skin-and-seed mixture. The highest value of the correlation factor was observed in cases of interaction of antioxidant activity and concentration of procyanidins (r = 0.83), antioxidant activity and concentration of anthocyanins (r = 0.78), and antioxidant activity and concentration of flavan-3-ols (r = 0.75). Among the flavan-3-ols, it was (+)-D-Catechin that prevailed in grape seeds, with its concentration in the Pinot Noir extract (OAO APF Fanagoria) reaching 468 mg/dm3. Maximum concentration of Epigallocatechin-gallate was observed in the Saperavi and Pinot Noir seeds. As regards the concentration of hydroxy-cinnamic acids in the seeds, n-coumaric acid (Ancellotta, Saperavi) stood apart among the others; gallic acid (Saperavi, Ancellotta) came forward among the hydroxy-benzoic acids. In the reviewed samples of grape seeds, procyanidins of groups В1 , В2 and В3 distinguished by high antioxidant activity prevailed. Prevalence of linoleic and oleic acids was established for grape oil extracted from the seeds of such red grape varieties as Cabernet Sauvignon, Pinot Noir and Saperavi. Maximum concentrations of oleic acid were found in the Pinot Noir and Riesling seeds. Palmitic and stearic acids were also available in rather high concentrations in the grape oil.

This article presents experimental data on physicochemical parameters (humidity, density, bulk density, effective viscosity) of grape pomace of various white and red grape varieties, subject to the processing technology applied. It was established that pomace humidity varies across a wide range of values, subject to the grape variety, grape processing technology and pressure equipment. A study of Chardonnay pomace was used to note the influence of pressure equipment and processing technology upon pomace humidity. The values of density and bulk density had a strong invert correlation with the humidity index. With increase of humidity, the values of density and bulk density lowered both for white and red pomace. It was shown that the value of effective viscosity of pomace of white grape varieties varied from 8.8 (Chardonnay) to 12.8 (Gewürztraminer) Pa·s; that of red grape varieties varied from 13.2 (Pinot Noir) to 15.8 (Saperavi, fermented pomace) Pa·s. Such variation may have been related to the varietal peculiarities of grapes, pomace humidity, and concentrations of high-molecular compounds. The highest total of phenolic compounds was observed in extracts of fermented Saperavi pomace. The total of pectic substances in grape pomace varied from 5.5 to 7.2% of dry weight for the white grape varieties, and from 4.4 to 5.9% for the red grapes. As for the concentrations of pectic substances, Riesling, Pinot Blanc and Sauvignon Blanc pomace were distinguished among the white grapes, and fermented Cabernet Sauvignon pomace – among the red grapes.

Of the most common childhood cancer, acute lymphoblastic leukemia (ALL), 15% of cases are caused by transformation of T cell progenitors (T-ALL). While survival rates have vastly improved for newly diagnosed T-ALL, substantial challenges remain in the treatment of relapsed disease and in the minimization of side-effects from central nervous system prophylaxis. Hence, the search for more effective, less toxic treatments continues. Homing receptors play multiple roles in cancer progression, yet little is known about the trafficking of T-ALL. Upon profiling homing receptor expression, we found high levels of the chemokine receptor CXCR4 on the surface of mouse and primary human T-ALL cells. Furthermore, T-ALL cells localized in close proximity to CXCL12-producing stromal cells in mouse femoral bone marrow. Deletion of Cxcl12 in vascular endothelial cells limited leukemia progression, suggesting a vascular niche for T-ALL. In parallel, we found CXCR4 expression to be essential for T-ALL maintenance and progression. Deletion of Cxcr4 in mouse T-ALL after disease onset led to disease remission and prolonged survival, and CXCR4 antagonism using the small molecule inhibitor AMD3465 suppressed human disease in a patient-derived xenograft model. Loss of CXCR4 signaling in T-ALL cells reduced Myc abundance, which was previously reported to regulate leukemia-initiating cell activity. In line with this, CXCR4-deficient T-ALL cells failed to establish disease when adoptively transferred into secondary hosts. Together, our findings highlight an important contribution of microenvironment in regulating T-ALL pathogenesis, and suggest targeting CXCL12:CXCR4 signaling as a powerful new strategy for treating this aggressive disease.