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Interactions of Different Urolithins With Bovine Serum Albumin
Backgound/Objectives: Urolithins (UROs) are the metabolites derived from the gut microbial action on ellagitannins and ellagic acid-rich foods. Following their absorption in the intestine, UROs are transported through the systemic circulation to various tissues where they can express their biological function as antimicrobial, anti-inflammatory, and anticancer agents. In addition to blood plasma, where they can be found as glucuronide and sulfate conjugates, they are also found in urine. Therefore, the interactions of UROs with serum proteins are of great clinical interest. Methods: A powerful technique for examining these urolithin-serum protein interactions is fluorescence spectroscopy. Bovine serum albumin (BSA) is a particularly suitable model protein because it is readily available, affordable, and similar to human serum albumin. This work aimed to study the binding of UROs (urolithin A, UROA and urolithin B, UROB) and their glucuronide conjugates (UROAG and UROBG) to BSA by quenching the intrinsic fluorescence of protein. Results: The spectra obtained showed that the binding process is influenced by the polyphenol's structure and the conjugation process with the glucuronide. The calculated Stern Vollmer binding constants (Ksv): UROA and UROB Ksv were 59236 ± 5706 and 69653 ± 14922, respectively, while for UROAG and UROBG, these values were 15179 ± 2770 and 9462 ± 1955, respectively, which showed that the binding affinity decreased with glucuronidation. Molecular docking studies confirmed that all of the studied molecules will bind favorably to BSA. The preferential binding site for both UROs and UROGs is Sudlow I, while UROs will also bind to Sudlow II. URO-Gs can bind to BSA in the cleft region with lower binding scores than for the Sudlow I binding site. Conclusion: The aglycone's higher hydrophobicity increases the binding affinity to BSA, thus reducing its bioavailability in the blood
Interactions of ultrashort laser pulses with hemoglobin: Photophysical aspects and potential applications
Hemoglobin (Hb), a life-sustaining and highly abundant erythrocyte protein, is not readily fluorescent. A few studies have already reported Two-Photon Excited Fluorescence (TPEF) of Hb, however, the mechanisms through which Hb becomes fluorescent upon interaction with ultrashort laser pulses are not completely understood. Here, we characterized photophysically this interaction on Hb thin film and erythrocytes using fluorescence spectroscopy upon single-photon/two-photon absorption, and UV-VIS single-photon absorption spectroscopy. A gradual increase of the fluorescence intensity, ending up with saturation, is observed upon prolonged exposure of Hb thin layer and erythrocytes to ultrashort laser pulses at 730 nm. When compared to protoporphyrin IX (PpIX) and oxidized Hb by H2O2, TPEF spectra from a thin Hb film and erythrocytes showed good mutual agreement, broad peaking at 550 nm, supporting hemoglobin undergoes degradation and that same fluorescent specie(s) originating from the heme moiety are generated. The uniform square shaped patterns of the fluorescent photoproduct exhibited the same level of the fluorescence intensity even after 12 weeks from the formation, indicating high photoproduct stability. We finally demonstrated the full potential of the formed Hb photoproduct with TPEF scanning microscopy towards spatiotemporally controlled micropatterning in HTF and single human erythrocyte labelling and tracking in the whole blood
Macrophages Provide Essential Support for Erythropoiesis, and Extracellular ATP Contributes to a Erythropoiesis-Supportive Microenvironment during Repeated Psychological Stress
Psychological stress is a significant contributor to various chronic diseases and affects multiple physiological processes including erythropoiesis. This study aimed to examine the tissue-specific contributions of macrophages and extracellular ATP, as a signal of disturbed tissue homeostasis, to erythropoiesis under conditions of repeated psychological stress. Adult male BALB/c mice were subjected to 2 h daily restraint stress for seven consecutive days. Clodronate-liposomes were used to deplete resident macrophages from the bone marrow and spleen two days prior to the first restraint procedure, as well as newly recruited macrophages, every third day for the duration of the experiment. Repeated stress induced a considerable increase in the number of erythroid progenitor cells as well as in the percentage of CD71+/Ter119+ and CD71−/Ter119+ cells in the bone marrow and spleen. Macrophage depletion completely abolished the stimulative effect of repeated stress on immature erythroid cells, and prevented stress-induced increases in ATP levels, P2X7 receptor (P2X7R) expression, and ectonucleotidase CD39 activity and expression in the bone marrow and spleen. The obtained results demonstrate the stimulative effects of repeated stress on erythroid cells, extracellular ATP levels, P2X7R expression, CD39 activity and expression within the bone marrow and spleen, as well as the essential role of macrophages in stress-induced changes
Nutrition and Physical Activity as Modulators of Osteosarcopenic Adiposity: A Scoping Review and Recommendations for Future Research
Osteosarcopenic adiposity (OSA) syndrome denotes the confluence of bone, muscle, and adipose tissue deterioration. Being a complex entity, numerous uncertainties about OSA still exist, despite the extensive research on the topic. Our objectives were to evaluate human studies addressing dietary intake/nutritional status and the quantity/types of physical activity related to OSA. The search in PubMed, Scopus, and Web of Science databases was conducted to examine relevant articles published from inception to the end of December 2022, utilizing the MeSH strings in the search strategy. Only studies published in English and conducted in humans (≥18 years) without chronic conditions (cancers, kidney/liver disease) or pregnancy were used. Book chapters, abstracts-only, and studies in which participants did not have all three body composition components measured to identify OSA or when body composition components could not be related to the independent/exposure variables were excluded. A total of n = 1020 articles were retrieved from all three databases and eight more from the reference lists. After the exclusion of duplicates and other unsuitable articles, n = 23 studies were evaluated. Among those, eleven were from epidemiological or cross-sectional studies relating nutrients/dietary intake or nutritional status with OSA. Another four examined the relationship between serum biomarkers (vitamin D and ferritin) with OSA, while eight articles presented the results of the interventional studies with resistance training. Overall, higher protein, calcium, potassium, and vitamins D and C intakes emerged as nutrients positively modifying OSA, along with a diet higher in fruits and low-fat dairy foods. Higher serum vitamin D and ferritin were respectively positively and negatively related to OSA. Resistance training was a safe intervention yielding several beneficial outcomes for the OSA syndrome in older women
Relationships between the structural characteristic of curcumins that affect cell proliferation of hepatocarcinoma cells
Relationships between the structural characteristic of curcumin and dimethoxycurcumin and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with the curcumin and dimethoxycurcumin resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated docking and the DFT method, suggest a structure-activity relationship between the activities of dimethoxycurcumin and curcumin structure and the apoptosis in HepG2 cell
Dietary Intake of Salt from Meat Products in Serbian Population
Salt intake above 5 g/day correlates with prevalence of hypertension and cardiovascular diseases (CVD). CVD, the leading cause of mortality and morbidity in Europe, account for 45% of all deaths, while, in Serbia in 2021, CVD accounted for 47.3%. The objective was to investigate salt content labelled on meat products from the Serbian market and estimate dietary exposure to salt from meat products in the Serbian population using consumption data. Data on salt content were collected from 339 meat products and classified in eight groups. Consumption data were collected using the EFSA EU Menu methodology (2017–2021) from 576 children and 3018 adults (145 pregnant women) in four geographical regions of Serbia. The highest salt content was in dry fermented sausages and dry meat, average 3.78 ± 0.37 g/100 g and 4.40 ± 1.21 g/100 g, respectively. The average intake of meat products is 45.21 ± 39.0 g/day and estimated daily salt intake from meat products per person is 1.192 g, which is 24% of the daily recommended amount. The actual meat product consumption and content of salt in meat products in Serbia present a risk factor for development of CVD and related comorbidities. A targeted strategy, policy and legislation for salt reduction are needed
Beneficial properties of zeolite
Our focus was to obtain an overall picture of the different beneficial properties of zeolite, based on its chemical and physical characteristics, which depend on zeolite absorption and exchange of ions. These characteristics make them very useful for various applications, including agriculture (as an animal feed additive and in food technology production), veterinary and human medicine, ecology, certain manufacturing, and cosmetics. Zeolite has pleiotropic effects, and the most important of them are detoxifying, antioxidant, and anti-inflammatory roles. We wanted to underline, with the review of the scientific literature, the positive medical beneficial effects of zeolite on the general health status
Immunohistochemical Pattern of Histone H2A Variant Expression in an Experimental Model of Ischemia–Reperfusion-Induced Acute Kidney Injury
Ischemia–reperfusion injury (IRI) is a frequent cause of AKI, resulting in vasoconstriction, cellular dysfunction, inflammation and the induction of oxidative stress. DNA damage, including physical DNA strand breaks, is also a potential consequence of renal IRI. The histone H2A variants, primary H2AX and H2AZ participate in DNA damage response pathways to promote genome stability. The aim of this study was to evaluate the immunohistochemical pattern of histone H2A variants’ (H2AX, γH2AX(S139), H2AXY142ph and H2AZ) expression in an experimental model of ischemia–reperfusion-induced acute kidney injury in spontaneously hypertensive rats. Comparing the immunohistochemical nuclear expression of γH2AX(S139) and H2AXY142ph in AKI, we observed that there is an inverse ratio of these two histone H2AX variants. If we follow different regions from the subcapsular structures to the medulla, there is an increasing extent gradient in the nuclear expression of H2AXY142ph, accompanied by a decreasing nuclear expression of γH2AX. In addition, we observed that different structures dominated when γH2AX and H2AXY142ph expression levels were compared. γH2AX was expressed only in the proximal tubule, with the exception of when they were dilated. In the medulla, H2AXY142ph is predominantly expressed in the loop of Henle and the collecting ducts. Our results show moderate sporadic nuclear H2AZ expression mainly in the cells of the distal tubules and the collecting ducts that were surrounded by dilated tubules with PAS (periodic acid–Schiff stain)-positive casts. These findings may indicate the degree of DNA damage, followed by postischemic AKI, with potential clinical and prognostic implications regarding this condition
Bioraspoloživost azotnog monoksida i antioksidativna odbrana kao ciljevi terapije u udruženom modelu akutne bubrežne slabosti i hipertenzije
Hipertenzija, koja se izmedu ostalog karakteriše i deficitom vasodilatatornog azotnog monoksida
(AM), mačajno pogoršava kliničku sliku postishernične akutne bubrežne slabosti (ABS) kod ljudi. Ponovno vraćanje krvi u bubrežno tkivo, samo po sebi dovodi do masovne produkcije slobodnih vrsta kiseonika (SVK) i pogoršanja ishemijske povrede. Ispitivali smo potencijalni zaštitni efekat primene donora AM-a, kao i uklanjanja SVK na sistemske i bubrežne hemodinamske parametre, kao i na strukturu i funkciju bubrega pacova sa urodenom hipertenzijom (PUH), kojima je izazivana postishemična ABS. Za navedene potrebe, PUH su dobijali donor AM, L-arginin, prirodni sakupljač SRK vitamin C (Vit C) ili sintetski mimetik enzima superoksid dismutase TEMPOL, tokom ishemije-reperfuzije bubrega u trajanju od 40 minuta. Tretman L-argininom je poboljšao sistemsku i bubreżnu hemodinarniku, ali nije uspeo da smanji ośtećenje bubrega. Nasuprot tome, intenzitet nekroze i dilatacije tubula su bili mačajno smanjeni kod pacova u ABS+Vit C grupi u poredenju sa kontrolnom ABS grupom. Uprkos smanjenju lipidne peroksidacije u plazmi, kao i renalnog vaskularnog otpora, tretman TEMPOL-om nije uspeo da ublaži reperfuzijom nastala oštećenja bubreżnog tkiva kod PUH. Naši rezultati ukazuju na to da SVK učestvuju u reperfuzionim oštećenjima bubrega, a da su sintetski mimetik superoksid dismutaze i donor AM neefikasni u zaštiti glomerula i tubula nakon nastanka ABS kod PUH. Sa druge strane, naši rezultati sugerišu daje Vit C, prirodni antioksidant, hemoprotektant umerenog zaśtitnog dejstva protiv ishemijsko-reperfuzionih povreda bubrega u hipertenzivnim okolnostima. Ova zaštita je većinski povezana sa direktnim uklanjanjem SVK.Hypertension, which is among others characterized by reducing of nitric oxide (NO) mediated vasodilatation, strongly aggravates postischemic acute kidney injury (AKI) in humans. Kidney reperfusion itself increases ischemic injury through the massive production of oxygen-free radicals. We investigated protective potential of NO supplementation and superoxide radical scavenging on systemic and renal haemodynamic parameters as well as kidney function and structure in spontaneously hypertensive rats (SHR) with induced postischemic AKI. For these purposes, SHR were subjected to NO donor L-arginine, natural oxidant scavenger vitamin C (Vit C) or synthetic superoxide dismutase mimetic TEMPOL during 40 minutes kidney ischaemia-reperfusion period. L-arginine supplementation improves systemic and renal hemodynamic but failed to reduce kidney tubular injuries. In opposite, intensity of tubular necrosis and dilatation was markedly reduced in AKI+Vit C group in comparison to AKI control. Despite blunting of lipid peroxidation in plasma and diminishing of renal vascular resistance, TEMPOL treatment also failed to reduce kidney tissue injuries induced by reperfusion in SHR. Our results suggest that superoxide radicals participate in kidney reperfusion injuries while synthetic superoxide dismutase and NO supplementation are ineffective in glomerular and tubular protection after AKI episode in hypertensive rats. On the other hand, our results promote natural antioxidant, vitamin C, as a moderately effective chemoprotectant against kidney ischemia-reperfusion injuries in hypertensive surrounding. Protection is mainly related to the direct superoxide radical scavenging