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The aetiology of polycystic ovary syndrome (PCOS) remains uncertain and thus dedicated studies are still of much importance. Patients in this group are at high risk for metabolic syndrome, diabetes and ischemic heart disease. Our goal was to use a dietary intervention, facilitating the regression of the disease, through the observation of lipid and hormonal profiles, carbohydrate metabolic parameters and metabolomics of plasma fatty acids. There were 39 Caucasian women with PCOS aged 26.76 ±5.08 that qualified for this study. Fatty acid profiles were investigated using gas chromatography. The results of plasma fatty acids were compared with the initial results and the control group. A three-month caloric reduction diet with low glycemic index (GI) reduces the level of nervonic acid and is a great alternative in PCOS therapy. The introduction of rapeseed oil and olive oil to the lowered GI reduction diet caused the increase in the ratio of average length chain fatty acids (C10:0, C14:0) and the enhancement of synthesis pathways for pentadecanoic acid (C15:0) and gamma-linolenic acid (GLA, C18:3n-6), but did not inhibit the synthesis of the derivatives of arachidic acid (C20:0). Additionally, a decrease in the level of nervonic acid (C24:1) was observed. Biochemical analysis of blood showed the improvement of plasma lipid fractions, but a significant reduction of androgen levels was not observed.

The aim of this study was to create a new computational model capable of evaluating the affinity of imprinted materials to the specific target. A 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone (L1), the main metabolite of voriconazole (L2) – a modern antifungal drug, was proposed as a template. In a computational analysis of polymerization systems composed of the template, the monomers and the cross-linker molecules the appropriate porogens were simulated. A non-covalent approach for the formation of a polymer matrix from eight functional monomers was employed in the theoretical and experimental studies. The binding affinities towards the template were measured for eight synthesized polymers. The experimental results confirmed that the proposed theoretical model properly showed isopropenylbenzene 1 as the most suitable monomer to synthesize the polymer with the best affinity to L1. The novel computational protocol was more suitable to predict the properties of polymer systems than the simple analysis of template–monomer interactions. On the basis of the polymerization complex PMC1 (template–isopropenylbenzene 1–cross-linker), the adsorption cavity was modeled and the intermolecular interactions of the template molecule and the other voriconazole metabolites inside the cavity were analyzed to get an insight into the polymer matrix selectivity. [ABSTRACT FROM AUTHOR]

This study is aimed at determining the content of water soluble vitamins in amateur sportsmen before and after the use of reduction diet. Twenty adult male amateur sportsmen aged between 20 and 43 qualified for this study. The participants adhered to individually adjusted reduction diets for 3 months. Diet supplements were excluded from the diet during that time. Vitamins were analyzed before and after the reduction diet using HPLC. The following vitamins were analyzed: B1, B2, B3, PP, B5, B6, B7, B9, B12 and vitamin C. Statistically significant increase of riboflavin in blood plasma (p=0.0254) and statistically significant (p=0.048) decrease in the concentration of niacin was found when compared to the period before the diet. Appropriate level of riboflavin can be obtained by the consumption of proper amount of diary in the diet. Supplementation with PP is advised and, in case of improper diet, the supplementation of B1, B7 and B12 may also be considered.

The crystal structure of 1-(3′-methylphenylazo)-2-naphthylamine 1 was determined by the X-ray diffraction method. No dynamic disorder was observed in the crystal of 1, and the azo group adopts trans azo conformation with six-membered ring formed by the intramolecular hydrogen bond. In the solid state, 13C CP/MAS NMR spectrum of its acetamide derivative 2 the double signals were found, in opposition to the other two acetamides of 1-arylazo-2-naphthylamines 3 and 4, in which only a simple pattern of resonances was detected. The DFT computations were employed to the conformational analysis of the title azocompounds. [Copyright &y& Elsevier]

Abstract Introduction Fluorides are common in the environment and are absorbed mostly in the stomach and gut, it can easily move through cell membranes and its accumulation can cause harmful effects in skeletal and soft tissues. One of the most important F- accumulation sites is the liver. The aim of this study was to determine whether F- can cause inflammation in rat liver by affecting the activity of antioxidant enzymes and changes in the synthesis of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). Materials and methods An in vivo model of prenatal and postnatal exposure to sodium fluoride (NaF) was used to carry out the experiment. Animals from control group received tap water to drink, while animals exposed to F- received drinking water containing NaF, 50 mg/L. In serum and liver we analyzed F- concentration, in liver - antioxidant enzymes activity, PGE2 and TXB2 concentration and immunolocalization of COX1 and COX2 proteins were measured. Results We observed significant changes in F- concentration only in liver. The results of this study showed that F- affects antioxidant enzymes activity, COX2 protein expression and PGE2 synthesis in liver. Also, in some regions of the liver of rats exposed to F-, the hepatocytes were diffusely altered, with changes resembling microvesicular steatosis. Conclusion Chronic exposure to F− during development causes an accumulation of this element in the liver and changes in antioxidant enzymes activity and cyclooxygenase expression. Long term exposure to this element is toxic to the liver and can cause disturbances in its homeostasis. Highlights • Exposure of rats to NaF caused an accumulation of F− in liver, but not in serum. • The changes may be caused by COX-2 dependent PGE2 synthesis. • F− caused inhibition of antioxidative enzymes activity. • Small vesicles were apparent in liver, indicating the early phase of steatosis. [ABSTRACT FROM AUTHOR]

Extreme inflammation that continues even after infections can lead to a cytokine storm. In recent times, one of the most common causes of cytokine storm activation has been SARS-CoV-2 infection. A cytokine storm leads to dysregulation and excessive stimulation of the immune system, producing symptoms typical of post-COVID syndrome, including chronic fatigue, shortness of breath, joint pain, trouble concentrating (known as "brain fog"), and even direct organ damage in the heart, lungs, kidneys, and brain. This work summarizes the current knowledge regarding inflammation and the cytokine storm related to SARS-CoV-2 infection. Additionally, changes in lipid metabolism and microbiota composition under the influence of inflammation in COVID-19, along with the possible underlying mechanisms, are described. Finally, this text explores potential health implications related to changes in eating behaviors and nutritional status in COVID-19 patients. Although research on the cytokine storm is still ongoing, there is convincing evidence suggesting that severe immune and inflammatory responses during the acute phase of COVID-19 may lead to long-term health consequences. Understanding these links is key to developing treatment strategies and supporting patients after infection.

We developed a procedure for selective 2,4-dimethylphenol, DMPh , direct electro-oxidation to 3,3',5,5'-tetramethyl-2,2'-biphenol, TMBh , a C-C coupled product. For that, we used an electrode coated with a product-selective molecularly imprinted polymer (MIP). The procedure is reasonably selective toward TMBh without requiring harmful additives or elevated temperatures. The TMBh product itself was used as a template for imprinting. We followed the template interaction with various functional monomers (FMs) using density functional theory (DFT) simulations to select optimal FM. On this basis, we used a prepolymerization complex of TMBh with carboxyl-containing FM at a 1:2 TMBh- to-FM molar ratio for MIP fabrication. The template-FM interaction was also followed by using different spectroscopic techniques. Then, we prepared the MIP on the electrode surface in the form of a thin film by the potentiodynamic electropolymerization of the chosen complex and extracted the template. Afterward, we characterized the fabricated films by using electrochemistry, FTIR spectroscopy, and AFM, elucidating their composition and morphology. Ultimately, the DMPh electro-oxidation was performed on the MIP film-coated electrode to obtain the desired TMBh product. The electrosynthesis selectivity was much higher at the electrode coated with MIP film in comparison with the reference nonimprinted polymer (NIP) film-coated or bare electrodes, reaching 39% under optimized conditions. MIP film thickness and electrosynthesis parameters significantly affected the electrosynthesis yield and selectivity. At thicker films, the yield was higher at the expense of selectivity, while the electrosynthesis potential increase enhanced the TMBh product yield. Computer simulations of the imprinted cavity interaction with the substrate molecule demonstrated that the MIP cavity promoted direct coupling of the substrate to form the desired TMBh product.

Research in recent years has shown that some species of predatory mites, considered to be typically associated with soil and litter, can also be found on plants. Such species include Blattisocius mali , which is an effective predator of acarid mites, nematodes and the eggs of moths and which can disperse by means of drosophilid fruit flies. Apart from soil and litter or storage, it has also been recorded on the bark of apple trees and the leaves of strawberries, thus suggesting its possible predation of/feeding on herbivorous mites and insects. Our goal was to examine whether B. mali could consume different development stages of two polyphagous herbivores, the two-spotted spider mite, Tetranychus urticae , and the western flower thrips, Frankliniella occidentalis , as well as the drosophilid fruit fly Drosophila hydei . In 24 h cage tests, single, starved B. mali females consumed all types of prey offered, i.e., the eggs, males and females of spider mites; the first-instar larvae and prepupae of thrips; and the eggs and first-instar larvae of fruit flies. The potential for B. mali to prey upon these insects and mites was confirmed. However, to estimate whether it can also effectively reduce their population, additional tests on the predator's survival, fecundity and prey preference are needed.

An electrochemical chemosensor for cilostazol (CIL) determination was devised, engineered, and tested. For that, a unique conducting film of the functionalized thiophene-appended carbazole-based polymer, molecularly imprinted with cilostazol (MIP-CIL), was potentiodynamically deposited on a Pt disk electrode by oxidative electropolymerization. Thanks to electro-oxidation potentials lower than that of CIL, the carbazole monomers outperformed pyrrole, thiophene, and phenol monomers, in this electropolymerization. The pre-polymerization complexes quantum-mechanical and molecular dynamics analysis allowed selecting the most appropriate monomer from the three thiophene-appended carbazoles examined. The electrode was then used as a selective CIL chemosensor in the linear dynamic concentration range of 50 to 924 nM with a high apparent imprinting factor, IF = 10.6. The MIP-CIL responded similarly to CIL and CIL's pharmacologically active primary metabolite, 3,4-dehydrocilostazol (dhCIL), thus proving suitable for their determination together. Simulated models of the MIP cavities binding of the CIL, dhCIL, and interferences' molecules allowed predicting chemosensor selectivity. The MIP film sorption of CIL and dhCIL was examined using DPV by peak current data fitting with the Langmuir (L), Freundlich (F), and Langmuir-Freundlich (LF) isotherms. The LF isotherm best described this sorption with the sorption equilibrium constant ( K LF ) for CIL and dhCIL of 12.75 × 10 -6 and 0.23 × 10 -6 M, respectively. Moreover, the chemosensor cross-reactivity to common interferences study resulted in the selectivity to cholesterol and dehydroaripiprazole of 1.52 and 8.0, respectively. The chemosensor proved helpful in determining CIL and dhCIL in spiked human plasma with appreciable recovery (99.3-134.1%) and limit of detection (15 nM).

We devised, fabricated, and tested differential pulse voltammetry (DPV) and impedance spectroscopy (EIS) chemosensors for duloxetine (DUL) antidepressant determination in human plasma. Polyacrylic nanoparticles were synthesized by precipitation polymerization and were molecularly imprinted with DUL (DUL-nanoMIPs). Then, together with the single-walled carbon nanotube (SWCNT) scaffolds, they were uniformly embedded in polytyramine films, i.e., nanoMIPs-SWCNT@(polytyramine film) surface constructs, deposited on gold electrodes by potentiodynamic electropolymerization. These constructs constituted recognition units of the chemosensors. The molecular dynamics (MD) designing of DUL-nanoMIPs helped select the most appropriate functional and cross-linking monomers and determine the selectivity of the chemosensor. Three different DUL-nanoMIPs and non-imprinted polymer (nanoNIPs) were prepared with these monomers. DUL-nanoMIPs, synthesized from respective methacrylic acid and ethylene glycol dimethyl acrylate as the functional and cross-linking monomers, revealed the highest affinity to the DUL analyte. The linear dynamic concentration range, extending from 10 pM to 676 nM DUL, and the limit of detection (LOD), equaling 1.6 pM, in the plasma were determined by the DPV chemosensor, outperforming the EIS chemosensor. HPLC-UV measurements confirmed the results of DUL electrochemical chemosensing.

The paper describes the formation of six aromatic N -(2-arylethyl)-2-methylprop-2-enamides with various substituents in benzene ring, viz., 4-F, 4-Cl, 2,4-Cl 2 , 4-Br, 4-OMe, and 3,4-(OMe) 2 from 2-arylethylamines and methacryloyl chloride in ethylene dichloride with high yields (46-94%). The structure of the compounds was confirmed by 1 H NMR, 13 C NMR, IR, and HR-MS. Those compounds were obtained to serve as functionalized templates for the fabrication of molecularly imprinted polymers followed by the hydrolysis of an amide linkage. In an exemplary experiment, the imprinted polymer was produced from N-(2-(4-bromophenyl)ethyl)-2-methylprop-2-enamide and divinylbenzene, acting as cross-linker. The hydrolysis of 2-(4-bromophenyl)ethyl residue proceeded and the characterization of material including SEM, EDS, 13 C CP MAS NMR, and BET on various steps of preparation was carried out. The adsorption studies proved that there was a high affinity towards the target biomolecules tyramine and L-norepinephrine, with imprinting factors equal to 2.47 and 2.50, respectively, when compared to non-imprinted polymer synthesized from methacrylic acid and divinylbenzene only.

Glioblastoma multiforme (GBM) represents the most malignant type of astrocytoma, with a life expectancy of two years. It has been shown that Poly (ADP-ribose) polymerase 1 (PARP-1) protein is over-expressed in GBM cells, while its expression in healthy tissue is low. In addition, perezone, a phyto-compound, is a PARP-1 inhibitor with anti-neoplastic activity. As a consequence, in the present study, both in vitro and computational evaluations of perezone and its chemically related compound, perezone angelate, as anti-GBM agents were performed. Hence, the anti-proliferative assay showed that perezone angelate induces higher cytotoxicity in the GBM cell line (U373 IC 50 = 6.44 μM) than perezone (U373 IC 50 = 51.20 μM) by induction of apoptosis. In addition, perezone angelate showed low cytotoxic activity in rat glial cells (IC 50 = 173.66 μM). PARP-1 inhibitory activity (IC 50 = 5.25 μM) and oxidative stress induction by perezone angelate were corroborated employing in vitro studies. In the other hand, the performed docking studies allowed explaining the PARP-1 inhibitory activity of perezone angelate, and ADMET studies showed its probability to permeate cell membranes and the blood-brain barrier, which is an essential characteristic of drugs to treat neurological diseases. Finally, it is essential to highlight that the results confirm perezone angelate as a potential anti-GBM agent.

Research aimed at developing potent di-indol-3-yl disulphides for cancer diseases makes use of various theoretical techniques to evaluate the drug-likeness parameters and the mode of action. A drug-likeness filter helps evaluate the therapeutic potency of four bis -indole derivatives, structurally related to 3,3'-methanediyl- bis -indole (DIM) but having the S-S instead of the methylene linker and showing a high inhibitory impact on the variants of cancer cell lines (among them HL-60 and DU-145). Based on in vitro experimental results for their close analogues, a correlation was found between the epidermal growth factor receptor kinase (EGFR) inhibition and the theoretical energy of complexation. Docking studies of ligands followed by molecular dynamics were performed at the ATP-binding site of EGFR tyrosine kinase to scrutinize the inhibition of the di-indol-3-yl disulphides at a molecular level. Derivatives with bromine or iodine substituents at C-5 positions of the indole moieties made strong complexes by interaction with the most important hinge region residues Met-793 and Cys-733. The inhibition model for EGFR kinase and the proposed procedures can be very informative in the biological testing of selected bis -indoles and may be useful for future research on effective inhibitors for the treatment of EGFR-related cancer.Communicated by Ramaswamy H. Sarma.

Introduction: Dietary fiber is one of the most important components of food. Fulfilling regulatory and nutritional functions for the intestinal microbiota, it appears to be an essential ingredient for people with a sedentary lifestyle., Aim: We hypothesized that regular intake of a snack containing high amounts of soluble fibre in parallel to a regular diet may rapidly improve bowel habits with simultaneous elevation of synthesis of short-chain fatty acids (SCFA)., Material and Methods: A total of 20 healthy volunteers, with a stool frequency of less than 3 spontaneous bowel movements per week, completed a 14-day double-blind, parallel-arm, randomized clinical trial with the intervention comprising daily intake of 2 doses (9.99% per 100 g or 13.91% per 100 g) of fibre. Food consumption was evaluated via 72-hour recall diaries at baseline and after 14 days of intervention. Gastrointestinal symptoms (abdominal comfort, distension, bloating, flatulence, stomach rumbling, number of bowel movements) were monitored via the IBS/VAS scale every day., Results: We found that the elevated fibre intake improved bowel habits significantly (defecation frequency increased from 0.28 to 0.87 times/day; p = 0.0002) in both study arms. After 14 days of the trial, an increase in SCFA concentration (for whole study group: acetic p < 0.036, propionic p < 0.019, and butyric acid p < 0.0012 compared to baseline parameters) with no adverse gastrointestinal symptoms was reported., Conclusions: Short-term, regular intake of a snack containing soluble fibre improves the SCFA synthesis and bowel habits in healthy people living a sedentary lifestyle. The exact mechanism behind this observation requires further investigation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

Molecularly imprinted polymer (MIP) nanoparticles-based differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) chemosensors for antiplatelet drug substance, cilostazol (CIL), and its pharmacologically active primary metabolite, 3,4-dehydrocilostazol (dhCIL), selective determination in human plasma were devised, prepared, and tested. Molecular mechanics (MM), molecular dynamics (MD), and density functional theory (DFT) simulations provided the optimum structure and predicted the stability of the pre-polymerization complex of the CIL template with the chosen functional acrylic monomers. Moreover, they accounted for the MIP selectivity manifested by the molecularly imprinted cavity with the CIL molecule complex stability higher than that for each interference. On this basis, a fast and reliable method for determining both compounds was developed to meet an essential requirement concerning the personalized drug dosage adjustment. The limit of detection (LOD) at the signal-to-noise ratio of S/N = 3 in DPV and EIS determinations using the ferrocene redox probe in a "gate effect" mode was 93.5 (±2.2) and 86.5 (±4.6) nM CIL, respectively, and the linear dynamic concentration range extended from 134 nM to 2.58 μM in both techniques. The chemosensor was highly selective to common biological interferences, including cholesterol and glucose, and less selective to structurally similar dehydroaripiprazole. Advantageously, it responded to dhCIL, thus allowing for the determination of CIL and dhCIL together. The EIS chemosensor appeared slightly superior to the DPV chemosensor concerning its selectivity to interferences. The CIL DPV sorption data were fitted with Langmuir, Freundlich, and Langmuir-Freundlich isotherms. The determined sorption parameters indicated that the imprinted cavities were relatively homogeneous and efficiently interacted with the CIL molecule., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bis-benzamidines are a diverse group of compounds with high potential in pharmacotherapy, and among them, pentamidine is a drug of great therapeutic significance in Pneumocystis jiroveci pneumonia (PJP) prophylaxis and therapy. Pharmacokinetic properties of these cationic species such as transport, acid/base equilibria, and interactions with potential target molecules are still of interest, especially for recently designed compounds. To broaden our knowledge drug-likeness, human serum albumin binding, and acidity constants (K a ) were experimentally and theoretically examined for five pentamidine analogues 1 - 5 with -NH-CO-chain-CO-NH-bridges of increasing length and O, N, and S atoms in the chain. The studied analogues display very marked activity against Pneumocystis carinii without cytotoxicity that inspired us to perform an in silico analysis of their mode of action based on the hypothesis that the small DNA groove of rich in adenine-thymine pairs is their molecular target. These studies allowed us to classify them as very promising lead molecules., (Copyright © 2021. Published by Elsevier B.V.)

Short-chain fatty acids (SCFAs) mediate the transmission of signals between the microbiome and the immune system and are responsible for maintaining balance in the anti-inflammatory reaction. Pregnancy stages alter the gut microbiota community structure, which also synthesizes SCFAs. The study involved 90 pregnant women, divided into two groups: 48 overweight/obese pregnant women (OW) and 42 pregnant women with normal BMI (CG). The blood samples for glucose, insulin, and HBA1c were analyzed as well as stool samples for SCFA isolation (C2:0; C3:0; C4:0i; C4:0n; C5:0i; C5:0n; C6:0i; C6:0n) using gas chromatography. The SCFA profile in the analyzed groups differed significantly. A significant positive correlation between C2:0, C3:0, C4:0n and anthropometric measurements, and between C2:0, C3:0, C4:0n, and C5:0n and parameters of carbohydrate metabolism was found. SCFA levels fluctuate during pregnancy and the course of pregnancy and participate in the change in carbohydrate metabolism as well. The influence of C2:0 during pregnancy on anthropometric parameters was visible in both groups (normal weight and obese). Butyrate and propionate regulate glucose metabolism by stimulating the process of intestinal gluconeogenesis. The level of propionic acid decreases with the course of pregnancy, while its increase is characteristic of obese women, which is associated with many metabolic adaptations. Propionic and linear caproic acid levels can be an important critical point in maintaining lower anthropometric parameters during pregnancy.

Appropriate nutrition is a key component of burn treatment and should be regarded as an integral part of the therapeutic process in burn patients. A nutritional intervention plan should not only allow for adequate quantities of energy and protein but also carefully consider the supply of macro- and micronutrients. As a result of the severe inflammatory response, oxidative stress, and hypermetabolic state, accompanied by often extensive exudation in burn patients, there is a considerable loss of macro- and micronutrients, including essential trace elements. This leads to certain complications, involving e.g. more frequent infections and impaired wound healing. Our current body of knowledge is still insufficient, and the studies carried out to date focus for the most part on the imbalances in trace elements, such as copper (Cu), selenium (Se), and zinc (Zn). Nevertheless, there are many other trace elements involved in immune functions, regulating gene expression or antioxidant defense, and many of those have not been properly investigated in a clinical setting. Due to the insufficient amount of unambiguous literature data and relatively few, often dated, studies carried out with small patient groups, further evaluation of macro- and microelements in burn patients seems indispensable, e.g. to bring up to date local nutritional protocols., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

New thiophene-carbazole functional and cross-linking monomers electropolymerizing at potentials sufficiently low for molecular imprinting of an electroactive aripiprazole antipsychotic drug were herein designed and synthesized. Numerous conducting molecularly imprinted polymer (MIP) films are deposited by electropolymerization at relatively low potentials by electro-oxidation of pyrrole, aniline, phenol, or 3,4-ethylenedioxythiophene (EDOT). However, their interactions with templates are not sufficiently strong. Hence, it is necessary to introduce additional recognizing sites in these cavities to increase their affinity to the target molecules. For that, functional monomers derivatized with substituents forming stable complexes with the templates are used. However, oxidation potentials of these derivatives are often, disadvantageously, higher than that of parent monomers. Therefore, we designed and synthesized new functional and cross-linking monomers, which are oxidized at sufficiently low potentials. The deposited MIP and non-imprinted polymer (NIP) films were characterized by PM-IRRAS and UV-vis spectroscopy and imaged with AFM. The structure of the aripiprazole pre-polymerization complex with functional monomers was optimized with density functional theory (DFT), and aripiprazole interactions with imprinted cavities were simulated with molecular mechanics (MM) and molecular dynamics (MD). MIP-aripiprazole film-coated electrodes were used as extended gates for selective determination of aripiprazole with the extended-gate field-effect transistor (EG-FET) chemosensor. The linear dynamic concentration range was 30-300 pM, and the limit of detection was 22 fM. An apparent imprinting factor of the MIP-1 was IF = 4.95. The devised chemosensor was highly selective to glucose, urea, and creatinine interferences. The chemosensor was successfully applied for aripiprazole determination in human plasma. The results obtained were compared to those of the validated HPLC-MS method., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Burned tissue is necrotic and it is surrounded by a zone of stasis and hyperaemia with changed cell metabolism. The removal of burned tissue using an electric knife releases large amounts of surgical smoke. The aim of the research was to analyse volatile, nonpolar, organic compounds that are released during the excision of burned tissue using an electric knife (mono- and bipolar). The study includes analysis from 40 solid-phase microextraction (SPME) fibres, exposed during 10 interventions (6 escharotomy and 4 necrectomy). The analysis of volatile compounds was performed using mass spectrometry gas chromatography (GCxGC-ToFMS).The total analysis covered 432 compounds, whereas after the removal of the "background" compounds - 153 volatile organic substances remained. The analysis of surgical smoke showed that, including derivatives, benzene constituted as much as 17.65% of all of the studied compounds. Cyclic compounds constituted on average 22.5% of the analysed substances, out of which cycloheptatrien constituted 20.26%. Alkanes, alcohols and their derivatives constituted nearly 25% of volatile organic compounds, with chloromethane constituting as much as 13.7%. Permutational multivariate analysis of variance (PERMANOVA) revealed statistically significant differences between escharotomy and necrectomy patients (F(1.9) = 5.91, p = 0.007).Our study revealed the presence of complex toxic hydrocarbon derivatives in surgical smoke. We also observed that the content of surgical smoke is different depending on the type of the conducted intervention. So far, no studies focusing on hazards posed by surgical smoke that is released during the resection of burned tissue are in the literature., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

The epidemic that broke out in Chinese Wuhan at the beginning of 2020 presented how important the rapid diagnosis of malnutrition (elevating during intensive care unit stay) and the immediate implementation of caloric and protein-balanced nutrition care are. According to specialists from the Chinese Medical Association for Parenteral and Enteral Nutrition (CSPEN), these activities are crucial for both the therapy success and reduction of mortality rates. The Chinese have published their recommendations including principles for the diagnosis of nutritional status along with the optimal method for nutrition supply including guidelines when to introduce education approach, oral nutritional supplement, tube feeding, and parenteral nutrition. They also calculated energy demand and gave their opinion on proper monitoring and supplementation of immuno-nutrients, fluids and macronutrients intake. The present review summarizes Chinese observations and compares these with the latest European Society for Clinical Nutrition and Metabolism guidelines. Nutritional approach should be an inseparable element of therapy in patients with COVID-19., Competing Interests: The authors declare no conflict of interest.

We aimed to systematically review the effectiveness of probiotic/synbiotic formulations to counteract cardiometabolic risk (CMR) in healthy people not receiving adjunctive medication. The systematic search (PubMed/MEDLINE/Embase) until 1 August 2019 was performed for randomized controlled trials in >20 adult patients. Random-effect meta-analysis subgroup and meta-regression analysis of co-primary (haemoglobin A1c (HbA1C), glucose, insulin, body weight, waist circumference (WC), body mass index (BMI), cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, and blood pressure) and secondary outcomes (uric acid, plasminogen activator inhibitor-1-PAI-1, fibrinogen, and any variable related to inflammation/endothelial dysfunction). We included 61 trials (5422 persons). The mean time of probiotic administration was 67.01 ± 38.72 days. Most of probiotic strains were of Lactobacillus and Bifidobacterium genera. The other strains were Streptococci , Enterococci , and Pediococci . The daily probiotic dose varied between 10 6 and 10 10 colony-forming units (CFU)/gram. Probiotics/synbiotics counteracted CMR factors (endpoint data on BMI: standardized mean difference (SMD) = -0.156, p = 0.006 and difference in means (DM) = -0.45, p = 0.00 and on WC: SMD = -0.147, p = 0.05 and DM = -1.21, p = 0.02; change scores on WC: SMD = -0.166, p = 0.04 and DM = -1.35, p = 0.03) in healthy persons. Overweight/obese healthy people might additionally benefit from reducing total cholesterol concentration (change scores on WC in overweight/obese: SMD: -0.178, p = 0.049). Poor quality of probiotic-related trials make systematic reviews and meta-analyses difficult to conduct and draw definite conclusions. "Gold standard" methodology in probiotic studies awaits further development.

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but gastrointestinal symptoms and hepatic injury have also been reported. The mechanism of liver injury is poorly understood and may result as a consequence of viral hepatitis, systemic inflammatory response, gut barrier and microbiome alterations, intensive care treatment or drug toxicity. The incidence of hepatopathy among patients with coronavirus disease 2019 (COVID-19) is unclear, but studies have reported liver injury in patients with SARS and Middle East respiratory syndrome (MERS). We aimed to systematically review data on the prevalence of hepatic impairments and their clinical course in SARS and MERS Coronaviridae infections. A systematic literature search (PubMed/Embase/Cinahl/Web of Science) according to preferred reporting items for systematic review and meta-analysis protocols (PRISMA) was conducted from database inception until 17/03/2020 for studies that evaluated the incidence of hepatic abnormalities in SARS CoV-1, SARS CoV-2 and MERS infected patients with reported liver-related parameters. A total of forty-three studies were included. Liver anomalies were predominantly mild to moderately elevated transaminases, hypoalbuminemia and prolongation of prothrombin time. Histopathology varied between non-specific inflammation, mild steatosis, congestion and massive necrosis. More studies to elucidate the mechanism and importance of liver injury on the clinical course and prognosis in patients with novel SARS-CoV-2 infection are warranted.

Nonalcoholic fatty liver disease (NAFLD) is becoming a major public health problem worldwide. The study aimed to evaluate the concentration of eicosanoids in serum and liver tissue during steatosis progression and to assess whether eicosanoid change scores may predict liver tissue remodeling. Thirty six eight-week-old male Sprague Dawley rats were enrolled and sacrificed at different stages of NAFLD. Eicosanoid concentrations, namely lipoxin A 4 , hydroxyeicosatetraenoic acids (HETE), hydroxyloctadecadienoic acids (HODE), protectin DX, Maresine1, leucotriene B 4 , prostaglandin E 2 , and resolvin D 1 measurement in serum and liver tissue with Agilent Technologies 1260 liquid chromatography were evaluated. For the liver and serum concentrations of 9-HODE and 13-HODE, the correlations were found to be strong and positive (r > 0.7, p < 0.05). Along with NAFLD progression, HODE concentration significantly increased, and change scores were more abundant in the liver. The moderate positive correlation between liver and serum (r = 0.52, p < 0.05) was also observed for resolvin E1. The eicosanoid concentration decreased during NAFLD progression, but mostly in serum. There were significant correlations between HETE concentrations in liver and serum, but their associations were relatively low and changes the most in liver tissue. Eicosanoids profile, predominantly 9-HODE and 13-HODE, may serve as a potential biomarker for NAFLD development.

Exposure of neural cells to harmful and toxic factors promotes oxidative stress, resulting in disorders of metabolism, cell differentiation, and maturation. The study examined the brains of rats pre- and postnatally exposed to sodium fluoride (NaF 50 mg/L) and activity of NADPH oxidase 4 (NOX4), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), concentration of glutathione (GSH), and total antioxidant capacity (TAC) in the cerebellum, prefrontal cortex, hippocampus, and striatum were measured. Additionally, NOX4 expression was determined by qRT-PCR. Rats exposed to fluorides (F-) showed an increase in NOX4 activity in the cerebellum and hippocampus, a decrease in its activity in the prefrontal cortex and hippocampus, and upregulation of NOX4 expression in hippocampus and its downregulation in other brain structures. Analysis also showed significant changes in the activity of all antioxidant enzymes and a decrease in TAC in brain structures. NOX4 induction and decreased antioxidant activity in central nervous system (CNS) cells may be central mechanisms of fluoride neurotoxicity. NOX4 contributes to blood-brain barrier damage, microglial activation, and neuronal loss, leading to impairment of brain function. Fluoride-induced oxidative stress involves increased reactive oxygen speciaes (ROS) production, which in turn increases the expression of genes encoding pro-inflammatory cytokines., Competing Interests: The authors declare they have no actual or potential competing financial interests.

Background: It was previously shown that a bodyweight reduction among patients with nonalcoholic fatty liver (NAFLD) was connected to the lower concentration of arachidonic and linoleic acid derivatives in their blood. We hypothesized that the concentration of these lipids was correlated with the extent of their body mass reduction and, thus, liver steatosis. Methods: We analyzed 68 individuals who completed the dietary intervention. Patients were divided into two groups depending on their body mass reduction (more or less than 7%). Before and after the dietary intervention, all patients had the following measurements recorded: body mass, waist circumference, stage of steatosis, fatty liver index, liver enzymes, lipid parameters, insulin and glucose. Concentrations of lipoxins A4 (LTX A4), hydroxyeicosatetraenoic fatty acids (5(S)-HETE, 12(S)-HETE and 16(S)-HETE), hydroxyoctadecaenoic acids (9(S)-HODE and 13(S)-HODE) and 5-oxo-eicosatetraenoic acid (5-oxo-ETE) were measured in serum samples collected before and after the dietetic intervention using high-performance liquid chromatography (HPLC). Results: Patients who reduced their body mass by more than 7% revealed a significant improvement in their steatosis stage, waist circumference, fatty liver index, triglycerides and cholesterol. Conclusion : A reduction in body mass by more than 7% but not by less than 7% revealed a significant improvement in steatosis stage; waist circumference; fatty liver index; and levels of triglycerides, cholesterol, 5-oxo-ETE and LTXA-4.

This work presents drug-likeness and the cardiotoxicity profiles of six potent pentamidine analogs 1-6 and three new compounds 7-9 as chemotherapeutics for therapy of Pneumocystis jiroveci pneumonia. A combination of experimental and computational approaches was used in the cardiotoxicity examination. The hERG trafficking and functionality of the hERG currents were tested by western blot analyses, immunofluorescent staining procedures, and patch-clamp electrophysiological assays. Cardiotoxicity combined with blocking the hERG K + channel was predicted, and then simulated by docking to the CSM-TM model 732 protein. Location of pentamidines in the proximity of Leu622, Thr623, Ser649, Tyr652, Ala653, and Phe656, and the high energies of interactions were in accordance with probable blocking of the hERG channel. However, in the biochemical experiments, no significant changes in I hERG densities and a minor effect on hERG maturation were observed. Predicted metabolic transformation of pentamidines with S atoms in the aliphatic linker leads to oxidation of one S atom, but those with the phenyl sulfanilide moiety can be oxidized to chinones. The tested pentamidines characterized by the presence of sulfur atoms or sulfanilide groups, have favorable drug-likeness parameters and are promising lead structures in the development of new potent chemotherapeutics against PJP., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders in industrialized Western countries. The prevalence of the disease is estimated to range from 4% to 46% worldwide. The aim of study was to develop an animal model with gradual NAFLD development., Methods: Sprague-Dawley rats were fed a high-fat and high-cholesterol (HFHCh) diet. The rats from the study and control groups were sacrificed after 2, 4, 8, 12, 16, and 20 weeks of dietary exposure., Results: Analysis of biochemical parameters showed that after only two weeks, ALT and cholesterol concentration in serum were elevated. After 4 weeks, TNF-α and HOMA-IR were significantly higher compared to the control group. NAFLD progression started after 12 weeks of diet-weight gain and increased LPS secretions were noticed. During the experiment, rats induced steatosis (from stage 0/1 after 4 weeks to stage 2/3 after 20 weeks), inflammation (from stage 0/1 after 4 weeks to stage 1/2 after 20 weeks), and fibrosis (from stage 1 after 12 weeks to stage 2 after 20 weeks)., Conclusion: We can assume that the presented model based on the HFHCh diet induced gradual development of NAFLD. We confirmed that the animal NAFLD model increases LPS secretions during disease progression., Competing Interests: The authors declare no conflict of interest.

Background: Existing data show a correlation between the profile of fatty acids, liver, and blood. Therefore, the aim of our study was to investigate the correlation between the fatty acids profile in blood pallets and the liver., Methods: The experiment was performed on 60 eight-week-old male Sprague-Dawley rats. The study group ( n = 30, 5 groups, 6 rats each) received a cholesterol diet; the control group ( n = 30, 5 groups, 6 rats each) received standard food for laboratory rats. The rats from both the study and control groups were sacrificed after 2, 4, 8, 12, and 16 weeks of dietary exposure. The fatty acids profile was measured using gas chromatography (GC)., Results: In both the control and study group, the highest correlations were observed in palmitoleic acid (RHO = 0.68), heptadecanoic acid (RHO = 0.65), vaccenic acid (RHO = 0.72), eicosapentaenoic acid (RHO = 0.68), docosapentaenoic acid (RHO = 0.77), and docosahexaenoic (RHO = 0.77). Among liver indexes, the highest correlations were desaturase-18 (0.61)., Conclusions: Fatty acids profile is a sensitive marker of the development of potentially pathological changes in the liver. The potential markers of fatty liver are: oleic acid, vaccenic acid, EPA, DHA, docosapentaenoic acid, and desaturase index (SCD-18 index).

Background and Objectives: The causative factors or conditions leading to increased intestinal permeability (IIP) have only been partly elucidated, suggesting excessive zonulin release to be a key factor among them. Likewise, it is known that athletic activity predisposes individuals towards the development of IIP; however, little is understood about the nature of this phenomenon. We decided to test the actual coincidence between IIP and increased stool zonulin (ISZ) in actively training athletes. Materials and Methods : We compared intestinal permeability tested with lactulose/mannitol differential absorption (lactulose/mannitol (L/M) test) and zonulin concentration in stool in 20 professional athletes (PRO), 9 amateur athletes (AMA), and 9 non-athletes (CTR). Results : The results confirmed that professional athletic activity showed significant positive association with intestinal permeability. ISZ was observed exclusively in athletes (CTR vs. AMA vs. PRO, respectively, 0% vs. 22% vs. 55%), and its prevalence was significantly higher in PRO than CTR. When we divided the participants into four categories related to exceeding the upper reference limits for both tested parameters (ISZ + or - and IIP + or -), significant differences were found between CTR and PRO; however, no significant differences were found between CTR and AMA or AMA and PRO. Conclusions : Our trial confirmed previous findings that professional athletic activity predisposes individuals to IIP. We also demonstrated that although ISZ was associated with intense training, there was no statistically significant association between ISZ and IIP in the tested group of professional athletes, which suggests the existence of additional mechanisms causing IIP., Competing Interests: All authors declare no conflict of interest.

Obesity and type-2 diabetes are often associated with nonalcoholic fatty liver disease (NAFLD). Soya isoflavones act as antidiabetic agents and protect against NAFLD. There are data suggesting that inulin may increase the plasma concentration and effect of soya isoflavones. The aim of the present study was to compare the effect of soya isoflavones, as opposed to the effect of soya isoflavones with inulin, on plasma lipid profile, liver morphology, and liver fatty acids in rats with induced type-2 diabetes mellitus. Data were collected on thirty-six male Sprague-Dawley rats divided into control and diabetic groups. Animals in the diabetic (DM) group were on a high-fat diet and were injected with low doses of streptozotocin. Animals in the control groups were fed a regular diet and were injected with a buffer. After the injections, the animals were divided into three groups of nondiabetic rats (nDM)-controls (c-nDM), rats treated with isoflavones (IS-nDM), and rats treated with isoflavones plus inulin (IS+IN-nDM)-and three parallel diabetic (DM) subgroups: controls (c-DM), rats treated with isoflavone (IS-DM), and rats treated with isoflavones plus inulin (IS+IN-DM). Hepatic steatosis and fibrosis were examined using hematoxylin-eosin staining and Mallory's trichrome methods respectively. Liver fatty acids were extracted and analyzed by gas chromatography. A lipid blood test was performed. The study showed significant changes in liver fatty acids, liver morphology, and plasma lipid profile. The estimated SCD-18 index significantly decreased in both the control and DM groups after isoflavone supplementation. The level of liver steatosis and fibrosis also decreased after isoflavone supplementation in the DM groups. The plasma lipid profile showed increased levels of HDL-C after isoflavone supplementation in the DM groups. These results support the protective use of isoflavones in liver steatosis and as beneficial to plasma lipid profile in individuals with diabetes. A novelty of this work is its comparison of supplementation using soya isoflavones with supplementation using both soya isoflavones and inulin. Surprisingly, additional supplementation with inulin modulates the positive effect of isoflavones.

We were interested whether fluorine, at the concentrations regarded as normal, can play a role in PCOS pathogenesis. The effect was not described in PCOS. Women with PCOS were diagnosed according to Rotterdam's criteria. The average age of 40 examined women with PCOS was 26.3 ± 5.5 years, BMI-29.16 ± 0.8, WHR-0.91 ± 0.08. Main Outcome Measures: ECLIA was used to analyse testosterone, FSH, LH, oestradiol, TSH, prolactin, insulin and SHBG. Fluorine content was analysed by potentiometry using ion selective electrode. Fluorine content in serum of women with PCOS did not statistically significantly differ from that of the control group and amounted to 0.224 ± 0.043 and 0.228 ± 0.023 ppm, respectively. There were significant differences in the levels of TSH and HOMA-IR between the groups. Based on the correlation matrix, a negative correlation with the level of SHBG protein and the level of glucose on fasting was showed for the group with a lower of fluorine, and a positive correlation with HDL level was observed in the group with higher concentration of fluorine. In the phenotype with a higher level of androgens, there was a negative correlation with triglycerides level and a positive correlation with HDL. Fluorine, even in concentrations regarded as proper, takes part in PCOS pathogenesis. It increases the synthesis of TSH and increases insulin resistance. Higher insulin resistance leads to the reduced synthesis of SHBG transport protein. Therefore, the key factor in PCOS pathogenesis is testosterone, but fluorine facilitates disruptions in carbohydrates and lipids metabolism leading to increased levels of androgens in blood., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale: Multiple drugs are known to induce metabolic malfunctions, among them second-generation antipsychotics (SGAs). The pathogenesis of such adverse effects is of multifactorial origin., Objectives: We investigated whether SGAs drive dysbiosis, assessed whether gut microbiota alterations affect body weight and metabolic outcomes, and looked for the possible mechanism of metabolic disturbances secondary to SGA treatment in animal and human studies., Methods: A systematic literature search (PubMed/Medline/Embase/ClinicalTrials.gov/PsychInfo) was conducted from database inception until 03 July 2018 for studies that reported the microbiome and weight alterations in SGA-treated subjects., Results: Seven articles reporting studies in mice (experiments = 8) and rats (experiments = 3) were included. Olanzapine was used in five and risperidone in six experiments. Only three articles (experiments = 4) in humans fit our criteria of using risperidone and mixed SGAs. The results confirmed microbiome alterations directly (rodent experiments = 5, human experiments = 4) or indirectly (rodent experiments = 4) with predominantly increased Firmicutes abundance relative to Bacteroidetes, as well as weight gain in rodents (experiments = 8) and humans (experiments = 4). Additionally, olanzapine administration was found to induce both metabolic alterations (adiposity, lipogenesis, plasma free fatty acid, and acetate levels increase) (experiments = 3) and inflammation (experiments = 2) in rodents, whereas risperidone suppressed the resting metabolic rate in rodents (experiments = 5) and elevated fasting blood glucose, triglycerides, LDL, hs-CRP, antioxidant superoxide dismutase, and HOMA-IR in humans (experiment = 1). One rodent study suggested a gender-dependent effect of dysbiosis on body weight., Conclusions: Antipsychotic treatment-related microbiome alterations potentially result in body weight gain and metabolic disturbances. Inflammation and resting metabolic rate suppression seem to play crucial roles in the development of metabolic disorders.

Fatty acid (FA) profiles in the plasma of patients with metabolic syndrome and chronic kidney disease (CKD) seem to be identical despite their different etiology (dietary mistakes vs. cachexia). The aim of this study was to compare both profiles and to highlight the differences that could influence the improvement of the treatment of patients in both groups. The study involved 73 women, including 24 patients with chronic kidney disease treated with haemodialysis, 19 patients with metabolic syndrome (MetS), and 30 healthy women in the control group. A total of 35 fatty acids and derivatives were identified and quantified by gas chromatography. Intensified elongation processes from acid C10:0 to C16:0 were noted in both groups (more intense in MetS), as well as an increased synthesis of arachidonic acid (C20:4n6), which was more intense in CKD. Significant correlations of oleic acid (C18:1n9), gamma linoleic acid (C18:3n6), and docosatetraenoate acid (C22:4n6) with parameters of CKD patients were observed. In the MetS group, auxiliary metabolic pathways of oleic acid were activated, which simultaneously inhibited the synthesis of eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) from alpha lipoic acid (ALA). On the other hand, in the group of female patients with CKD, the synthesis of EPA and DHA was intensified. Activation of the synthesis of oleic acid (C18: 1n9 ct) and trans-vaccinic acid (C18:1) is a protective mechanism in kidney diseases and especially in MetS due to the increased concentration of saturated fatty acid (SFA) in plasma. The cause of the increased amount of all FAs in plasma in the CKD group, especially in the case of palmitic (C16:0) and derivatives stearic (C18:0) acids, may be the decomposition of adipose tissue and the progressing devastation of the organism, whereas, in the MetS group, dietary intake seems to be the main reason for the increase in SFA. Moreover, in MetS, auxiliary metabolic pathways are activated for oleic acid, which cause the simultaneous inhibition of EPA and DHA synthesis from ALA, whereas, in the CKD group, we observe an increased synthesis of EPA and DHA. The higher increase of nervonic acid (C24:1) in CKD suggests a higher degree of demyelination and loss of axons.