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Polyphenol extraction in microwave reactor using by-product of Thymus serpyllum L. and biological potential of the extract
No full textIn the present study, polyphenol extraction from Thymus serpyllum by-product (herbal dust) in microwave reactor was optimized through varying extraction time, ethanol concentration and solid-to-solvent ratiovia determination of total polyphenol and flavonoid contents, and antioxidant activity, using response surface methodology and a central composite design. Total polyphenol and flavonoids contents, as well as antioxidant activity of the extracts were statistically significantly affected by ethanol concentration and solid-to-solvent ratio. However, extraction time had statistically significant influence only on polyphenol yield. The extraction conditions that maximized polyphenol recovery were 48% ethanol and 0.0402 g/mL solid-to-solvent ratio during 86 s of microwave-assisted extraction, and under these conditions total polyphenol content was estimated to be 57.2 mg of gallic acid equivalents (GAE)/L, while measured value was 58.1 ± 3.2 mg GAE/L. Polyphenol content (HPLC analysis), antioxidant, antimicrobial and antispasmodic potential of the extract prepared under these optimal extraction conditions were evaluated. Rosmarinic acids, luteolin 7-O-glucuronide, caffeic acid, apigenin glucuronide, 6-hydroxyluteolin 7-O-glucoside, 6,8-di-C-glucosylapigenin, and traces of chlorogenic acid were quantified in the extract (descending order of content). The selected extract inhibited 95% ± 0.9 of lipid peroxidation in β-Carotene and linoleic acid emulsion. It was more effective against tested Gram-positive bacteria than against Gram-negative and showed dose-dependent antispasmodic activity on spontaneous contractions, acetylcholine- and potassium chloride-induced contractions. Microwave-assisted extraction could be selected as a successful technique for polyphenol extraction from wild thyme by-product. Biological activities shown in the study open the possibility of potential application of the extract in pharmaceutical, food, functional food and cosmetic products
Extracellular Hemoglobin: Modulation of Cellular Functions and Pathophysiological Effects
Get PDFHemoglobin is essential for maintaining cellular bioenergetic homeostasis through its ability to bind and transport oxygen to the tissues. Besides its ability to transport oxygen, hemoglobin within erythrocytes plays an important role in cellular signaling and modulation of the inflammatory response either directly by binding gas molecules (NO, CO, and CO2) or indirectly by acting as their source. Once hemoglobin reaches the extracellular environment, it acquires several secondary functions affecting surrounding cells and tissues. By modulating the cell functions, this macromolecule becomes involved in the etiology and pathophysiology of various diseases. The up-to-date results disclose the impact of extracellular hemoglobin on (i) redox status, (ii) inflammatory state of cells, (iii) proliferation and chemotaxis, (iv) mitochondrial dynamic, (v) chemoresistance and (vi) differentiation. This review pays special attention to applied biomedical research and the use of non-vertebrate and vertebrate extracellular hemoglobin as a promising candidate for hemoglobin-based oxygen carriers, as well as cell culture medium additive. Although recent experimental settings have some limitations, they provide additional insight into the modulatory activity of extracellular hemoglobin in various cellular microenvironments, such as stem or tumor cells niches
Gender Difference in SARS-CoV-2 Stimulation of Hyperinflammatory Response in Patients with COVID-19
Get PDFBackground: Although women and men have the same prevalence, men with
COVID-19 are more at risk for worse outcomes and death, independent of age.
Methods: To observe the hyperinflammatory response regarding sex, we will measure
the levels of inflammatory cytokines: interleukin-6 (IL-6), IL-1β, tumor necrosis
factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), IL-10, interferon-
gamma (IFN-γ), IL-8, transforming growth factor-beta 1 (TGF-β1), analyzed by
ELISA, in plasma of 130 COVID-19 patients at diagnosis and correlate them with clinical
parameters. Besides, we checked the quality of life of patients up to 3 months
after hospitalization.
Results: Pro-inflammatory IL-6 was significantly (p<0.01) increased in male COVID-19
patients compared to healthy male volunteers (4.7-fold) and female COVID-19 patients
(1.75-fold). IL-6 was positively correlated to INR, aPTT (p<0.001), and ferritin (p<0.05),
while INR with CRP (p<0.05). IL-8 was significantly increased in female COVID-19 patients
compared to healthy female volunteers (p<0.01, 2.5-fold) and male COVID-19 patients
(p<0.05). TNF-α was significantly (p<0.05) increased in male COVID-19 patients
compared to healthy male volunteers. MCP-1 and IFN-γ were significantly increased
in female COVID-19 patients compared to healthy female volunteers (p<0.01). Anti-inflammatory
TGF-β1 was decreased in COVID-19 patients regardless of gender. Most
patients were men (75%) with chronic disorders (59%, mostly hypertension). COVID-19
reduced their social (32%) and physical activities (34%) after 6 weeks of diagnosis, but
further on reduced in additional 3 months (social 55%) with depression (22%).
Conclusions: Inflammatory response is generally increased in COVID-19 patients
with specific cytokines in accordance with gender
Targeting Stress Erythropoiesis Pathways in Cancer
Get PDFCancer-related anemia (CRA) is a common multifactorial disorder that adversely affects the quality of life and overall prognosis in patients with cancer. Safety concerns associated with the most common CRA treatment options, including intravenous iron therapy and erythropoietic-stimulating agents, have often resulted in no or suboptimal anemia management for many cancer patients. Chronic anemia creates a vital need to restore normal erythropoietic output and therefore activates the mechanisms of stress erythropoiesis (SE). A growing body of evidence demonstrates that bone morphogenetic protein 4 (BMP4) signaling, along with glucocorticoids, erythropoietin, stem cell factor, growth differentiation factor 15 (GDF15) and hypoxia-inducible factors, plays a pivotal role in SE. Nevertheless, a chronic state of SE may lead to ineffective erythropoiesis, characterized by the expansion of erythroid progenitor pool, that largely fails to differentiate and give rise to mature red blood cells, further aggravating CRA. In this review, we summarize the current state of knowledge on the emerging roles for stress erythroid progenitors and activated SE pathways in tumor progression, highlighting the urgent need to suppress ineffective erythropoiesis in cancer patients and develop an optimal treatment strategy as well as a personalized approach to CRA management
Extraction of individual associative memory related dominant theta frequency for personalized transcranial brain stimulation
Get PDFNon-invasive brain stimulation (NIBS) has gained increased interest in research and therapy of associative memory (AM) and its impairments. However, the one-size-fits-all approach yields inconsistent findings, thus putting forward the need for the development of personalized frequency-modulated NIBS protocols to increase the focality and the effectiveness of the interventions. There have been only a few attempts to deliver theta frequency-personalized tES. The current study explores the feasibility of determining dominant individual theta-band frequency (ITF) based on AM task evoked EEG activity. In a sample of 42 healthy young adults, we extracted the frequencies (2-15 Hz, in 0.5 Hz steps) with the highest event-related spectral perturbation from the EEG recorded during successful encoding in the AM task. The developed method for extraction of the dominant theta-band frequency based on the AM-evoked EEG changes is able to reliably determine the AM-related ITF and can be used for personalization of the oscillatory NIBS techniques.Preprint:[https://www.biorxiv.org/content/10.1101/2022.03.07.483124v2
Dietary patterns, caloric restrictions for management of cardiovascular disease and cancer; a brief review
Get PDFCardiovascular disease (CVD) and cancers are overall still identified as the two most prevalent non-communicable diseases globally. Their prevention and potential reversal (in particular CVD risk) was seen effective with the modification of dietary intake that was applied in several different populations. Although the findings from epidemiological studies provide support that adhering to dietary patterns such as the Mediterranean diet can reduce incidence and prevalence of CVD and some forms of cancer, the mechanistic aspects of disease modulation associated with both diseases can be seen in dietary management. Several studies have already explored the potential modes of action of certain nutrients in well controlled large clinical trials. However, the clinical trials designed to determine the effects of adhering to a particular diet are relatively hard to conduct and these studies are faced with several obstacles particularly in the populations that are identified with a high risk of CVD or different cancers. Therefore, it is important to understand potential underlying and shared mechanisms of action and to explore how healthy dietary patterns may modulate the occurrence, initiation, and progression of such diseases. The aim of this review is to summarise and conceptualize the current understanding relating to healthy dietary patterns, and briefly discuss the opportunities that epigenetic research may bring and how it may assist to further interpret epidemiological and clinical evidence
Epidemiology of Toxoplasmosis in SERBIA: A Cross-Sectional Study on Blood Donors
Get PDFToxoplasmosis is a globally distributed parasitic zoonosis, affecting approximately one third of the human population. Epidemiological studies on toxoplasmosis conducted in Serbia so far have been focused on women of childbearing age, without a clear insight into the prevalence in the general population. We conducted a cross-sectional study in a representative sample of the healthy adult population consisting of 1095 blood donors of both genders to establish the prevalence and risk factors for Toxoplasma gondii infection. Data on the demographic and clinical characteristics of all study participants, as well as on their lifestyle habits, were collected by means of a questionnaire. The overall prevalence of infection was 20.5% (224/1095) and the avidity of the specific IgG antibodies detected was high in a vast majority of the seropositive donors (98.2%). Interestingly, the remaining 1.8% of the specific IgG positive samples were of borderline avidity (4/224), in complete absence of specific IgM. The multivariate logistic regression analysis showed that independent risk factors included age (from OR (95% CI) 1.9 (1.13–3.28) in the 30–39 age group, to 6.8 (3.27–14.24) in the age group of >60 years), suburban living (OR (95% CI) 2.2 (1.43–3.34)) and contact with soil (OR (95% CI) 1.4 (1.01–1.94)). This first large-scale study on toxoplasmosis in the general population in Serbia shows the lowest prevalence ever reported in this country. Moreover, the novel perspective on risk factors provides an updated basis for future prevention programs
Transforming growth factor-beta1 and myeloid-derived suppressor cells: A cancerous partnership
Get PDFTransforming growth factor-beta1 (TGF-beta 1) plays a crucial role in tumor progression. It can inhibit early cancer stages but promotes tumor growth and development at the late stages of tumorigenesis. TGF-beta 1 has a potent immunosuppressive function within the tumor microenvironment that largely contributes to tumor cells' immune escape and reduction in cancer immunotherapy responses. Likewise, myeloid-derived suppressor cells (MDSCs) have been postulated as leading tumor promoters and a hallmark of cancer immune evasion mechanisms. This review attempts to analyze the prominent roles of both TGF-beta 1 and MDSCs and their interplay in cancer immunity. Furthermore, therapies against either TGF-beta 1 or MDSCs, and their potential synergistic combination with immunotherapies are discussed. Simultaneous TGF-beta 1 and MDSCs inhibition suggest a potential improvement in immunotherapy or subverted tumor immune resistance
Exosomes and exosome-mimetics as targeted drug carriers: Where we stand and what the future holds?
No full textExosomes are a sub-group of extracellular vesicles, playing an important part in a cell-cell communication in many physiological and pathological conditions. Their size and competence for transferring material to recipient cells make them a promising nanocarrier for clinical use. Their non-immunogenic nature, similar to the body's own structure make them far superior transporters compared to liposomes and polymeric nanoparticles. This review, will provide an overview of exosome biogenesis, biological role, and purification methods. The focus of this manuscript will be to summarize specific applications of exosomes and exosome-mimetics as drug delivery systems in pharmaceutical drug development. We will describe drug-loading approaches, in vivo and in vitro exosome tracing methods, specific modifications and examples of the delivery of therapeutic and imaging molecules from a variety of biological origins. Challenges in the translation of exosome-based drug carriers to clinical use will also be discussed in this review
Oral supplementation with organically modified clinoptilolite during prepartum period influences the redox status of peripheral blood and colostrum of primiparous dairy cows
Get PDFRedox imbalance in peripartum period influences health of dairy cows and their foetus and, through the colostrum, health of new-born calves. Oxidative stress in cattle can be suppressed by dietary supplementation with natural minerals, and we investigated the effect of supplementation with organically modified clinoptilolite on redox status parameters in healthy pregnant primiparous dairy cows. Holstein cows were randomly assigned to receive daily oral drenching, with 1 L of water containing either 0 g/L (n = 14; control group) or 150 g/L of clinoptilolite (n = 17; supplemented group). Treatment lasted from 24 ± 4 days prior to parturition until 2 days postpartum (pp). Blood samples were collected on days 24 ± 4 (–24 D) and 4 ± 2 (–4 D) prior to parturition and on days 1 (+1 D), 2 (+2 D), and 7 (+7 D) pp, and colostrum were collected at 2, 12, 24 and 36 h pp. Total antioxidant capacity, lipid peroxides, and advanced oxidation protein products (AOPP) levels were determined in peripheral blood plasma, erythrocytes, and colostrum whey. The concentration of antioxidants in the peripheral blood of supplemented cows was increased by 41% and 19% on (+2 D) and (+7 D), respectively, while the concentration of lipid peroxides on (+7 D) was lowered by 57% compared with the control group. In addition, this supplementation increased erythrocyte AOPP level on (–4 D) 61%) and colostral lipid peroxides level (90%) at 24 h pp. The results of this study showed that applied short-term supplementation with clinoptilolite influences redox homeostasis and may contribute to effective adaptation of primiparous cows to redox imbalance in the peripartum period. Highlights Short-term dietary supplementation with clinoptilolite in the prepartum period modulates redox homeostasis of the dairy cows’ blood plasma. Short-term dietary supplementation with clinoptilolite contributes to adaptation of dairy cows to redox imbalance in the peripartum period. Short-term dietary supplementation with clinoptilolite increase the level of lipid peroxides in colostrum of dairy cows