Pigmentation Levels Affect Melanoma Responses to Coriolus versicolor Extract and Play a Crucial Role in Melanoma-Mononuclear Cell Crosstalk

Melanoma, the malignancy originating from pigment-producing melanocytes, is the most aggressive form of skin cancer and has a poor prognosis once the disease starts to metastasize. The process of melanin synthesis generates an immunosuppressive and mutagenic environment, and can increase melanoma cell resistance to different treatment modalities, including chemo-, radio- or photodynamic therapy. Recently, we have shown that the presence of melanin pigment inhibits the melanoma cell response to bioactive components of Coriolus versicolor (CV) Chinese fungus. Herein, using the same human melanoma cell line in which the level of pigmentation can be controlled by the L-tyrosine concentration in culture medium, we tested the effect of suppression of melanogenesis on the melanoma cell response to CV extract and investigated the cell death pathway induced by fungus extract in sensitized melanoma cells. Our data showed that susceptibility to CV-induced melanoma cell death is significantly increased after cell depigmentation. To the best of our knowledge, we are the first to demonstrate that CV extract can induce RIPK1/RIPK3/MLKL-mediated necroptosis in depigmented melanoma cells. Moreover, using the co-culture system, we showed that inhibition of the tyrosinase activity in melanoma cells modulates cytokine expression in co-cultured mononuclear cells, indicating that depigmentation of melanoma cells may activate immune cells and thereby influence a host anticancer response.

1H-NMR-Based Analysis for Exploring Knee Synovial Fluid Metabolite Changes after Local Cryotherapy in Knee Arthritis Patients

Rehabilitation using cryotherapy has widely been used in inflammatory diseases to relieve pain and decrease the disease activity. The aim of this study was to explore the metabolite changes in inflammatory knee-joint synovial fluids following local cryotherapy treatment (ice or cold CO2). We used proton nuclear magnetic resonance (1H NMR) spectroscopy to assess the metabolite patterns in synovial fluid (SF) in patients with knee arthritis (n = 46) before (D0) and after (D1, 24 h later) two applications of local cryotherapy. Spectra from aqueous samples and organic extracts were obtained with an 11.75 Tesla spectrometer. The metabolite concentrations within the SF were compared between D1 and D0 using multiple comparisons with the application of a false discovery rate (FDR) adjusted at 10% for each metabolite. A total of 32 metabolites/chemical structures were identified including amino acids, organic acids, fatty acids or sugars. Pyruvate, alanine, citrate, threonine was significantly higher at D1 vs D0 (p < 0.05). Tyrosine concentration significantly decreases after cryotherapy application (p < 0.001). We did not observe any effect of gender and cooling technique on metabolite concentrations between D0 and D1 (p > 0.05). The present study provides new insight into a short-term effect of cold stimulus in synovial fluid from patients with knee arthritis. Our observations suggest that the increased level of metabolites involved in energy metabolism may explain the underlying molecular pathways that mediate the antioxidant and anti-inflammatory capacities of cryotherapy.

First Scandinavian case of successful pregnancy during nitisinone treatment for type 1 tyrosinemia

BackgroundType 1 tyrosinemia is a hereditary metabolic disease in which tyrosine metabolites damage the liver and kidneys. Nitisinone medication revolutionized the treatment, but the effects of the drug during human pregnancy are unknown.Case presentationA 17-year-old tyrosinemia patient became pregnant. Nitisinone was continued throughout pregnancy with a varying serum concentration and dose ranging from 0.8 to 1.4 mg/kg/day. Blood tyrosine remained stable until it increased in late pregnancy. α-fetoprotein increased to 284 μg/L without new changes in liver. Urine succinylacetone remained undetectable, but there were signs of possibly reoccurring kidney tubulopathy. Fetal ultrasound monitoring was normal throughout the pregnancy and the newborn healthy. After the delivery, α-fetoprotein normalized, but tyrosine continued to rise for up to 1 year. The child is developing normally.ConclusionsPregnancy during nitisinone was successful, but tailoring of the drug dose and possibly reappearing complications, as also increasing serum tyrosine concentration after delivery warranted intensified surveillance.

Synthesis of Silver Nanoparticles Using Tyrosine as Reductor and Capping Agent

Synthesis and stability of silver nanoparticles (AgNPs) using tyrosine as a reducing and capping agent have been done. Synthesis of AgNPs was performed by mixing silver nitrate (AgNO3) solution as a precursor with tyrosine amino acid and heating it in a boiling water bath until characterized by the appearance of color change from colorless to yellow. Variations in pH, concentration, and reaction time affecting the formation of AgNPs were studied using UV-Vis spectrophotometry in the wavelength range of 300-700 nm as the main device. The synthesis was successfully conducted at pH 11 for 45 min with the optimum tyrosine concentration was 3 mM for 0.5 mM AgNO3. The optimum mole ratio AgNO3 0.5 mM to tyrosine 3 mM was 1:6. TEM and PSA characterizations showed that the particle was a round shape and 29.5 nm is average size, respectively.

INFLUENCE OF TECHNOLOGICAL METHODS ON AMINO ACID COMPOSITION OF WHITE TABLE WINE MATERIALS

Исследован аминокислотный состав столового сухого белого виноматериала Пино Блан, полученного сбраживанием виноградного сусла расой активных дрожжей штамма WT-1 (Германия) с последующей выдержкой молодого виноматериала на дрожжевой гуще в течение 30 сут. Установлено, что в анализируемом виноматериале доминирует пролин (422 мг/дм3). Количество аминокислот аланина и аспарагина составило 67,2 и 57,6 мг/дм3 тирозина и серина 18,4 и 17,7 мг/дм3 метионина и изолейцина 16,2 и 14,4 мг/дм3 соответственно. Глутаминовой кислоты содержится в 3 раза меньше пролина. Оклейка молодого виноматериала привела к снижению концентрации аминокислот независимо от строения и химических свойств: глицина в 3,5 раза аланина, изолейцина, серина, фенилаланина, гистидина от 2,0 до 2,7 раза аспарагина, валина, треонина, тирозина, лизина, цистина и цистеина от 1,3 до 1,9 раза. Концентрация пролина снизилась незначительно c 422 до 389 мг/дм3. После выдержки молодого виноматериала на дрожжевой гуще в течение 1 мес. концентрация большинства аминокислот не повысилась. Обработка виноматериала бентонитом привела к дальнейшему снижению концентрации аминокислот в 1,52,0 раза. Отмечено уменьшение в 1,72 раза количества цистина и цистеина, обусловливающих формирование мышиного тона в виноматериалах. В 1,57 раза снизилась концентрация тирозина в 2,7 и 2,3 раза гистидина и серина соответственно. Проведенное исследование будет способствовать дальнейшим работам по стабилизации концентрации основных аминокислот в виноматериалах. The amino acid composition of table dry white wine material Pinot Blanc was studied, obtained by fermentation of grape must with a race of active yeast strain WT-1 (Germany), followed by exposure of the young wine material to yeast for 30 days. It was established that proline (422 mg/dm3) prevails in the analyzed wine material. The number of amino acids of alanine and asparagine was 67,2 and 57,6 mg/dm3 tyrosine and serine 18,4 and 17,7 mg/dm3 methionine and isoleucine 16,2 and 14,4 mg/dm3, respectively. Glutamic acid is 3 times less than proline. Pasting of young wine material led to a decrease in the concentration of amino acids, regardless of structure and chemical properties: glycine by 3,5 times alanine, isoleucine, serine, phenylalanine, histidine from 2,0 to 2,7 times asparagine, valine, threonine, tyrosine, lysine, cystine and cysteine from 1,3 to 1,9 times. The proline concentration decreased slightly from 422 to 389 mg/dm3. After aging the young wine material on yeast for 1 month, the concentration of most amino acids did not increase. Processing of wine material with bentonite led to a further decrease in the concentration of amino acids by 1,52,0 times. There was a 1,72-fold decrease in the amount of cystine and cysteine. The tyrosine concentration decreased 1,57 times 2,7 and 2,3 times histidine and serine, respectively. The study will contribute to further work on stabilizing the concentration of basic amino acids in wine materials.

Assessment of Propionibacterium Metabolic Activity on Protein Substrate of Sarcoplasmic Fraction in Hydrobionts’ Muscle Tissue

As a result of the conducted scientific researches, the authors analyzed methodical aspects of studying the proteolytic properties of Propionibacterium freudenreichii subsp. shermanii-KM 186 – the representatives of the probiotic group of microorganisms, which allowed not only to evaluate the enzymatic activity of the objects of study but also to discover how physical and chemical factors influence the proteins hydrolysis intensity in sarcoplasmic and myofibrillary fractions of hydrobionts’ muscle tissue. During the experiment which aimed at assessing the possibility of using individual protein fractions of fish muscle tissue as a substrate for proteolysis by Propionibacterium bacteria for the spectrophotometry analysis of their enzymatic activity, it was found that the sarcoplasmic fraction can be used as a substrate for studying the microorganisms’ proteolytic activity. Determination of the information content of tyrosine concentration measuring by spectrophotometry to characterize the proteolytic activity of bacterial suspensions showed that to assess the enzymatic activity of living microorganisms culture it is advisable to use not the absolute values of the bacterial suspension activity, expressed in μmolTYR/ml×min or the tyrosine concentration in the sample (μmol/L), but the change in the tyrosine level in comparison with its primary values. This way of expressing the results will allow us to assess the prevalence of processes (dissimilation/assimilation). In addition, the experiment revealed the characteristic response of the Propionibacterium bacteria’s metabolic activity to changes in the physical and chemical conditions.

Effects of Maternal Undernutrition during Mid-Gestation on the Yield, Quality and Composition of Kid Meat Under an Extensive Management System

Nutritional status during mid-gestation is often ignored under extensive husbandry. This study aimed to examine the effect of maternal undernutrition during mid-gestation on kid meat production under an extensive system. Twenty-seven goats (45 ± 3 d of gestation) were randomly assigned to an unrestricted group (100% of nutrient requirements), or a restricted group (60% of nutrient requirements from 45 to 100 d of gestation, and then re-alimented to 100%). Among the offspring, 16 eligible kids (eight per treatment) were selected, based on birth type and survival, and were harvested to evaluate the meat yield, quality, and composition at 90 d after birth. Maternal undernutrition reduced the body weight and size, average daily gain and hot carcass weight of the kids (p < 0.05). The lightness of the meat at 45 min postmortem was increased (p = 0.029) in the restricted kids. Apart from an increase in tyrosine concentration (p = 0.046), the proximate composition and the amino acid and fatty acid profiles were unaffected in the restricted kids (p > 0.05). Overall, maternal undernutrition during mid-gestation decreased the yield of kid meat, but did not significantly modify the quality and composition. These results highlight the importance of nutrient status during mid-gestation in the meat production of small ruminants under an extensive regime.