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Oligopyridine based copper(II) complexes are of interest to scientists as possible anticancer agents due to promising cytotoxic and DNA binding/cleaving properties. In this study, copper(II) complex [Cu(phendione)L2]·C2H5OH with 1,10-phenanthroline-5,6-dione (phendione) and 4,5-dichloro-isothiazole-3-carboxylic acid (HL) was synthesized and characterized by elemental analysis, IR-spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. According to X-ray diffraction data, obtained compound is mononuclear complex with square pyramidal coordination environment of the central atom which is surrounded by two isothiazolate molecules and one phendione ligand. The X-ray diffraction data are confirmed by IR-spectroscopy data showing the presence of characteristic stretching vibration bands of the carbonyl and carboxyl groups of oligopyridine ligand and isothiazolate ions, respectively. Density functional theory (DFT) calculations for complex were carried out using the ADF software package to perform geometry optimization and frequency calculations that were in a good agreement with experimental IR spectrum. Cytotoxicity of complex and initial reagents was tested in vitro against HepG2 (human hepatocellular carcinoma) and MCF-7 (human breast adenocarcinoma) cell lines. The complex showed high dose-dependent cytotoxic activity with the IC50 values of 0.60±0.03 µM and 0.96±0.13 µM, respectively, which is higher than the activity of cisplatin against these cell lines. The activity of the complex is due to the presence of phendione ligand, which exhibits a similar cytotoxic activity.

The radical SAM superfamily (RSS), arguably the most functionally diverse enzyme superfamily, is also one of the largest with ~700K members currently in the UniProt database. The vast majority of the members have uncharacterized enzymatic activities and metabolic functions. In this Perspective, we describe RadicalSAM.org, a new web-based resource that enables a user-friendly genomic enzymology strategy to explore sequence-function space in the RSS. The resource attempts to enable identification of isofunctional groups of radical SAM enzymes using sequence similarity networks (SSNs) and the genome context of the bacterial, archaeal, and fungal members provided by genome neighborhood diagrams (GNDs). Enzymatic activities and in vivo functions frequently can be inferred from genome context given the tendency for genes of related function to be clustered. We invite the scientific community to use RadicalSAM.org to (i) guide their experimental studies to discover new enzymatic activities and metabolic functions, (ii) contribute experimentally verified annotations to RadicalSAM.org to enhance the ability to predict novel activities and functions, and (iii) provide suggestions for improving this resource.

Crude β-D-galactosidase from Lactobacillus leichmannii 313 was used to synthesise galacto-oligosaccharides (GOS) from lactose. Using an initial lactose concentration of 170 g/L, the yield of GOS was 52 g/L (i.e. 62% lactose conversion) after 2 h of enzymatic reaction. The highest number of unique individual GOS were generated after 48 h of reaction. ESI-MS and HPAEC analysis of the GOS enriched fractions obtained from 48 h mixtures showed the presence of sugars with degrees of polymerization (DP) ranging from 2 to 6. Further analysis (by NMR spectroscopy) of GOS in fraction 3 (containing ~ 96% w/w GOS) showed non-reducing terminals that were mostly Galp; and reducing ends that were →4)-Glcp, and →6)-Glcp. The most abundant internal linkages in fraction 3 were deduced to be →3)-Galp-(1→, and →6)-Galp-(1→. The predominance of β-D-(1→3, or 6) linkages in GOS fractions suggests that β-D-galactosidase from LL313 is suitable for generating unique GOS from lactose.

HMG-CoA reductase (Hmgcr) is the rate-limiting enzyme in the mevalonate pathway and is inhibited by statins. In addition to cholesterol, Hmgcr activity is also required for synthesizing nonsterol isoprenoids, such as dolichol, ubiquinone, and farnesylated and geranylgeranylated proteins. Here, we investigated the effects of Hmgcr inhibition on nonsterol isoprenoids in the liver. We have generated new genetic models to acutely delete genes in the mevalonate pathway in the liver using AAV-mediated delivery of Cre-recombinase (AAV-Cre) or CRISPR/Cas9 (AAV-CRISPR). The genetic deletion of Hmgcr by AAV-Cre resulted in extensive hepatocyte apoptosis and compensatory liver regeneration. At the biochemical level, we observed decreased levels of sterols and depletion of the nonsterol isoprenoids, dolichol and ubiquinone. At the cellular level, Hmgcr-null hepatocytes showed ER stress and impaired N-glycosylation. We further hypothesized that the depletion of dolichol, essential for N-glycosylation, could be responsible for ER stress. Using AAV-CRISPR, we somatically disrupted dehydrodolichyl diphosphate synthase subunit (Dhdds), encoding a branch point enzyme required for dolichol biosynthesis. Dhdds-null livers showed ER stress and impaired N-glycosylation, along with apoptosis and regeneration. Finally, the combined deletion of Hmgcr and Dhdds synergistically exacerbated hepatocyte ER stress. Our data show a critical role for mevalonate-derived dolichol in the liver and suggest that dolichol depletion is at least partially responsible for ER stress and apoptosis upon potent Hmgcr inhibition.

The sources of the nitric oxide (NO) formation in the uterus and the dynamics of changes in its content in different periods of organ functioning in human and animals are analyzed. The biochemical mechanisms of NO action on the myometrium contractile activity, the significance of NO in the physiological processes during pregnancy and labor, the importance of mitochondria as a reliable NO source in the smooth muscle and the possible ways of NO influence on Ca2+ transport and bioenergetic processes in mitochondria are considered. The authors’ data concerning ionic and membrane mechanisms of NO action on Ca2+-homeostasis of uterine myocytes, identification of nitric oxide in uterine smooth muscle mitochondria, biochemical characteristics of the NO-synthase reaction and the possible role of NO in the regulation of Ca2+ transport in these subcellular structures and in the electron transport chain functioning are presented and discussed.

Extracellular vesicles (EVs) are secreted by most cell types under both physiological and pathological conditions and were proposed to be actively involved in intercellular communication. The mode of EVs action is dependent on their cargos composition. EVs play an important role in tumor initiation, recurrence, metastasis and therapeutic resistance. EVs marker proteins Alix and Tsg101 and cortactin are the binding partners of adaptor protein Ruk/CIN85. The present study aims to analyze the regulatory effects of EVs produced by 4T1 cells with overexpression (RukUp) or down-regulation (RukDown) of adaptor protein Ruk/CIN85 on proliferation rate, migration and invasion activity of parental 4T1 WT cells. EVs from conditioned medium of 4T1 RukUp or RukDown cells were isolated by differential centrifugation followed by further purification using Exo-spin™ kit (Cell Guidance Systems). The number and size of EVs were characterized by NTA (Malvern Panalytical NanoSight NM300) instrument. The content of marker proteins and Ruk/CIN85 in isolated EVs was analyzed by Western-blotting. The viability, migration and invasion activity of 4T1 WT cells were studied using MTT-test, scratch-test and Boyden chamber assay, respectively. It was demonstrated for the first time that adaptor protein Ruk/CIN85 is a constitutive component of EVs produced by 4T1 cells. It was also shown that EVs produced by 4T1 cells with different levels of Ruk/CIN85 expression are characterized by a specific profile of the content of its multiple molecular forms. It turned out that the ability of EVs to modulate the proliferative activity, motility and invasiveness of 4T1 WT cells was tightly correlated with the biological properties of 4T1 cells that produce EVs (highly aggressive 4T1 RukUp cells or weakly invasive 4T1 RukDown cells). Our data suggest that adaptor protein Ruk/CIN85 is not only a constitutive component of cargos composition of EVs produced by tumor cells but, depending on its content in EVs, plays an active role in the control of carcinogenesis.

The aim of this work was the development of an efficient analytical method for the determination of bisoprolol and related substances in the finished drug product using HPLC/DAD. Different bonded phases (alkyl and phenyl) with variable pore sizes and column dimensions, temperatures, and mobile phases with variable pH and additives were tested. Experiments that included using Hypersil 3 BDS C18 100 × 4 mm, 3 mm; Zorbax SB C18 150 × 4.6 mm, 3.5 mm; Acquity UPLC BEH C18 50 × 2.1 mm, 1.7 mm; and Xterra MS C18 100 × 4.6 mm, 3.5 mm gave the best results when considering the separation and resolution of the tested analytes within a reasonable run time. The method using Xterra MS C18 100 × 4.6 mm, 3.5 mm was validated as the most suitable when taking into account the mobile phase preparation and versatility, analysis time, and equipment maintenance.Validation parameters (linearity, accuracy, precision, selectivity) confirmed the method as suitable for its intended use.

In this study, the preparation of tin(II) oxide/reduced graphene oxide (SnO/rGO) hybrid electrodes was simultaneously performed by a one-pot electrodeposition process for the first time by using a single cell. The morphological and structural characterizations of SnO/rGO were performed by scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDS), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). Additionally, the electrocatalytic activities of the electrode materials for the determination of DA were tested by the linear sweep voltammetry technique. Furthermore, the amperometric sensing of DA was carried out with a detection limit of 0.32 µM. The results suggest that our fabricated biosensor exhibited an ultrahigh sensitivity, low detection limit, and excellent selectivity.

The role of an amphiphilic environment in the functional regulation of integral membrane proteins is well appreciated but how specific amphiphilic surrounding influences the conformational plasticity and function of a protein is less obvious. We focus on the Salmonella phosphoglycerate transport system (pgt)-encoded outer membrane protease E (PgtE), which plays an important role in tissue infiltration and survival of Salmonella enterica. Despite our understanding of its physiological functions, elucidation of its enzymatic behavior in response to the immediate amphiphilic surrounding is lacking. We monitor the proteolytic activity of PgtE reconstituted in Zwittergent 3-12 detergent micelles or a 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) bilayer and examine factors that influence its activity. We find, to our surprise, that PgtE, which is thought to elicit a rapid response toward various substrates, showed hysteretic enzymatic behavior, characterized by a prominent lag phase prior to achieving the exponential steady state in its detergent-stabilized form as well as in the outer membrane embedded native state in live bacteria. The lag phase was abolished under three conditions: preformation of an inactive detergent-stabilized PgtE-substrate complex without lipopolysaccharide (LPS), LPS-bound detergent-stabilized PgtE that had reached steady state velocity, or PgtE reconstituted into a POPC bilayer environment. Interestingly, detergent- and bilayer-stabilized PgtE showed comparable steady-state activity. And strikingly, lipopolysaccharide (LPS) becomes nonessential for the activation of PgtE when the protein is reconstituted in the phospholipid bilayer, contrasting a long-standing notion that LPS is required for proteases belonging to the omptin family to be proteolytically active. These findings suggest intriguing biological nuances for the proteolytic function of PgtE that were not well appreciated previously and offer new perspectives that may generally be applicable for omptins.

Owed to current environmental concerns and crude oil price fluctuations, the design of feasible substitutes to petroleum-based polymeric materials is a major challenge. A lot of effort has been focused on transforming natural vegetable oils (VOs), which are inexpensive, abundant, and sustainable, into polymeric materials. Different nanofillers have been combined with these bio-based polymer matrices to improve their thermal, mechanical, and antibacterial properties. The development of multifunctional nanocomposites materials facilitates their application in novel areas such as sensors, medical devices, coatings, paints, adhesives, food packaging, and other industrial appliances. In this work, a brief description of current literature on polymeric nanocomposites from vegetable oils reinforced with carbon nanomaterials is provided, in terms of preparation, and properties. Different strategies to improve the nanomaterial state of dispersion within the biopolymer matrix are discussed, and a correlation between structure and properties is given. In particular, the mechanical, thermal, and electrical properties of these natural polymers can be considerably enhanced through the addition of small quantities of single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), graphene (G), or its derivatives such as graphene oxide (GO) or fullerenes (C60). Finally, some current and potential future applications of these materials in diverse fields are briefly discussed.

Objectives The present study set out to build a machine learning model to incorporate conventional quality control (QC) rules, exponentially weighted moving average (EWMA), and cumulative sum (CUSUM) with random forest (RF) algorithm to achieve better performance and to evaluate the performances the models using computer simulation to aid laboratory professionals in QC procedure planning. Methods Conventional QC rules, EWMA, CUSUM, and RF models were implemented on the simulation data using an in-house algorithm. The models’ performances were evaluated on 170,000 simulated QC results using outcome metrics, including the probability of error detection (Ped), probability of false rejection (Pfr), average run length (ARL), and power graph. Results The highest Pfr (0.0404) belonged to the 1–2s rule. The 1–3s rule could not detect errors with a 0.9 Ped up to 4 SD of systematic error. The random forest model had the highest Ped for systematic errors lower than 1 SD. However, ARLs of the model require the combined utility of the RF model with conventional QC rules having lower ARLs or more than one QC measurement is required. Conclusions The RF model presented in this study showed acceptable Ped for most degrees of systematic error. The outcome metrics established in this study will help laboratory professionals planning internal QC.

COVID-19 is the most devastating pandemic situation we have experienced in our age, affecting all systems. Although it affects all systems, it shows its most important effect through thrombophilia. Therefore, the possible cause of sudden death due to COVID-19 may be embolism caused by thrombophilia. D-dimer amounts increase due to COVID-19. The thrombosis is associated with sudden death in COVID-19 disease in populations. Since individuals with thrombophilia will be more prone to death due to COVID-19, it may be appropriate to administer low doses of Clexane (Enoxaparin sodium) or low-weight heparin for prophylactic purposes in order to consider these individuals at high risk and to prevent deaths. Moreover, in order not to risk the lives of healthcare professionals with thrombophilia, it would be appropriate to keep them away from individuals with COVID-19 disease and to employ them in different healthcare services according to their fields of expertise. It should also not be forgotten that different symptoms related to COVID-19 appear day by day, these different symptoms probably show that the virus has undergone mutations in order to survive, but no matter what, its effect on thrombophilia has not been eliminated yet. This compilation aims to present the reasons and causes of death due to COVID-19, possible treatment options, and thrombophilia panel tests and new parameters that may have a place in the meticulous interpretation of these tests and possible etiopathology in the light of current information. Therefore, presenting this information in a rational manner and keeping the parameters of the thrombophilia panel under strict control predict that the deaths due to the virus will be partially reduced.

PURPOSE: Anterior cruciate ligament (ACL) injuries are the most common in sports and have doubled in the past 20 years. This study aimed to analyze the latest trends and changes in training programs for ACL injury prevention.METHODS: In this study, literature was searched using academic search sites, such as ‘PubMed’, ‘Google Scholar’, and ‘Wiley Online Library’. The literature published between 2015 and 2021 was used.RESULTS: Eleven papers were selected based on the literature selection criteria. Five warm-up exercise papers and six ACL injury prevention training program papers emphasized neuromuscular training.CONCLUSIONS: The ACL injury prevention program can be applied in warm-up exercises and training programs. It consists of an exercise form that includes multidimensional components such as plyometrics, muscle strength, balance, and agility. The key to the ACL injury prevention program is to reflect multidimensional components in neuromuscular training and to obtain a significant effect, and it is recommended to participate in regular training for 12-18 sessions and at least 6 months. In addition, it is suggested to utilize the ACL injury prevention program presented in this study until an individual study for ACL injury prevention by sports type is conducted.

PURPOSE: This study aimed to investigate the relationship of physical activity level with arterial stiffness, cerebral blood flow, and cognitive function in young adults.METHODS: Forty-six young adults participated in this cross-sectional study. Physical activity levels were assessed for seven consecutive days using accelerometers. To assess arterial stiffness, the carotid–femoral artery pulse wave velocity (cfPWV) and augmentation index (AIx) were measured. Cognitive function was assessed using the Stroop Color-Word test, and cerebral blood flow was evaluated using near-infrared spectroscopy devices during the cognitive function test.RESULTS: AIx was inversely associated with axis-1 counts, vector magnitude counts, moderate-intensity physical activity (MPA) time, and moderate-to-vigorous intensity physical activity (MVPA) time (r≤-0.31, p≤.04). The AIx adjusted to the heart rate of 75 beats per minute was inversely correlated with axis-1 counts, vector magnitude counts, step counts, MPA time, and MVPA time (r≤-0.33, p≤.03). There was no relationship between cfPWV and physical activity level parameters (r≤0.10, p≥.51). The difference between oxygenated and deoxygenated hemoglobin levels was positively related to axis-1 counts, step counts, MPA time, and MVPA time (r≥0.31, p≤.04). Regarding cognitive function, the response time for the presented words was negatively associated with step counts (r=-0.42, p

PURPOSE: This study evaluates the differences in the expression of genes frequently analyzed in the field of exercise science between the skeletal muscle tissue and various cell types that comprise the skeletal muscle tissue.METHODS: We summarized the genes and proteins expressed in the skeletal muscle that were published in “Exercise Science” journal from 2015 to present. Thereafter, we selected 15 genes and proteins that were the most analyzed genes and proteins in the skeletal muscle. These genes and proteins were horizontally compared for expression differences in skeletal muscle components and cultured cells based on NCBI Gene Expression Omnibus DataSets.RESULTS: The most analyzed genes (encoding analyzed proteins) in skeletal muscle tissues in “Exercise Science” were PPARGC1A, PPARD, MTOR, MAP1LC3A, MAP1LC3B, PRKAA1, AKT1, SLC2A4, MAPK1, COX4I1, MAPK14, MEF2A, MAPK8, RPS6KB1, and SOD1. Among them, PPARGC1A, AKT1, SLC2A4, MAPK1, and COX4I1 were specifically expressed in the skeletal muscle. However, expression of other genes was found to be significantly affected in other cell types of the skeletal muscle tissue.CONCLUSIONS: Genes such as PPARGC1A, which are specifically expressed in the skeletal muscle, may be analyzed without pretreating (such as perfusion) the skeletal muscle tissue. However, expression of other genes may depend on the skeletal muscle cell type. Thus, in such instances, pretreatment, such as perfusion and isolation, should be considered.

PURPOSE: This study aimed to examine changes in pulmonary function induced by an internal nasal dilator (IND) and to determine whether an IND enhances exercise performance.METHODS: Young, healthy men (n=13) were randomly assigned either an IND or control (CON) session to perform a pulmonary function test (PFT). All participants then completed treadmill exercise tests that consisted of maximal and submaximal running with or without an IND.RESULTS: Some variables of PFTs were increased in men that used INDs compared to those in the CON group (p

PURPOSE: This study aimed to examine the associations between participation in physical education (PE) classes and the psychological well-being and sleep satisfaction of Korean adolescents.METHODS: Cross-sectional data from 127,804 Korean adolescents (aged 12–18 years) who participated in the 2016 and 2017 Korea Youth Risk Behavior Web-based Surveys (KYRBS) were analyzed. The exploratory variable was the frequency of participation in PE classes every week, while the dependent variables included the psychological well-being and sleep satisfaction, as assessed by the KYRBS questionnaire. Sex- and grade-stratified logistic regression analyses were conducted to generate the odds ratios (ORs) and 95% confidence intervals (CI).RESULTS: Overall 16.9% of adolescents reported that they did not participate in PE classes while 33.0% reported participating for more than three times a week. After adjusting for the academic achievements, family’s economic status, consumption frequency of breakfast and highly caffeinated drinks, and physical activity level, a greater participation in the PE classes was found to be associated with happiness in a dose-response fashion in both sexes and grades (p

Alzheimer’s disease manifests itself in brain tissue by neuronal death, due to aggregation of β-amyloid, produced by senile plaques, and hyperphosphorylation of the tau protein, which produces neurofibrillary tangles. One of the genetic markers of the disease is the gene that translates the presenilin-2 protein, which has mutations that favor the appearance of the disease and has no reported crystallographic structure. In view of this, protein modeling is performed using prediction and structural refinement tools followed by an energetic and stereochemical characterization for its validation. For the simulation, four reported mutations are chosen, which are Met239Ile, Met239Val, Ser130Leu, and Thr122Arg, all associated with various functional responses. From a theoretical analysis, a preliminary bioinformatic study is made to find the phosphorylation patterns in the protein and the hydropathic index according to the polarity and chemical environment. Molecular visualization was carried out with the Chimera 1.14 software, and the theoretical calculation with the hybrid quantum mechanics/molecular mechanics system from the semi-empirical method, with Spartan18 software and an AustinModel1 basis. These relationships allow for studying the system from a structural approach with the determination of small distance changes, potential surfaces, electrostatic maps, and angle changes, which favor the comparison between wild-type and mutant systems. With the results obtained, it is expected to complement experimental data reported in the literature from models that would allow us to understand the effects of the selected mutations.

PURPOSE: Arterial stiffness is an independent risk factor for cardiovascular disease and inversely associated with flexibility. Self-myofascial release (SMR) using a foam roller is a popular intervention to improve flexibility, restore the muscles, fascia, tendons, and ligaments, and regain soft-tissue extensibility. This study aimed to investigate whether a single bout of SMR has a beneficial effect on arterial stiffness and the function of the autonomic nervous system and the relationships among these variables in young and middle-aged women by age.METHODS: Ten healthy young (23.20±0.59 years) and 10 middle-aged women (44.50±0.91 years) completed an instructed SMR using a foam roller. Brachial-ankle pulse wave velocity (baPWV), augmentation index (AIx), trunk flexibility, shoulder flexibility, heart rate variability, including standard deviation of normal R-R intervals (SDNN), and the root mean square of the standard deviation of the time between heartbeats (RMSSD) were measured before and after one 30-minutes bout of SMR.RESULTS: After one bout of SMR, trunk and shoulder flexibility increased in both groups of women, while AIx decreased significantly (from 6.9±2.9 to -1.9±4.6%, p=.0072, young women group; from 22.1±3.4 to 14.7±1.7%, p=.0049, middle-aged women group). However, the baPWV, RMSSD, and SDNN did not change. In the analysis of correlations between all measured variables, changes in AIx showed negative correlations with flexibility and SDNN.CONCLUSIONS: This study suggests that one bout of SMR using a foam roller positively affected arterial stiffness in women by reducing AIx and improving flexibility.

BACKGROUND/AIMS: Liver is considered as the vital organ in the body as it performs various essential functions. Following an injury to the liver, the repair process even though initially beneficial becomes pathogenic when it is not controlled appropriately. Extensive accumulation of extracellular matrix (ECM) components can ultimately lead to cirrhosis and liver failure. Thus, the ideal strategy to treat a liver injury is to generate new hepatocytes replacing damaged cells without causing excessive ECM deposition. The objective of this study was to evaluate the potential of mesenchymal stem cells, conditioned media and murine epidermal growth factor (m-EGF) in liver regeneration following partial hepatectomy in a rat model. METHODS: The animals were anaesthetized and a midline laparotomy was done. The liver was exposed and the left lateral and median lobes were ligated and resected out (about 65-70% of total liver mass). The muscles and skin were sutured in routine fashion and thus the rat model of partial hepatectomy was prepared. The animal models were equally distributed into 4 different groups namely A, B, C and D and treated with PBS, conditioned media, mesenchymal stem cells and epidermal growth factor respectively. The liver regeneration was assessed based on clinical, haemato-biochemical, colour imaging, histopathological and immune-histochemical parameters. RESULTS: Partial hepatectomy model with surgical removal of 65-70% liver lobe was standardized and successfully used in this study. Alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin, transaminases were significantly higher (P

International audience; This Review focuses on the structure–function relationship of radical S-adenosyl-l-methionine (SAM) enzymes involved in the assembly of metallocofactors corresponding to the active sites of [FeFe]-hydrogenase and nitrogenase [MoFe]-protein. It does not claim to correspond to an extensive review on the assembly machineries of these enzyme active sites, for which many good reviews are already available, but instead deals with the contribution of structural data to the understanding of their chemical mechanism (Buren et al. Chem. Rev. 2020, 142 (25) 11006−11012; Britt et al. Chem. Sci. 2020, 11 (38), 10313–10323). Hence, we will present the history and current knowledge about the radical SAM maturases HydE, HydG, and NifB as well as what, in our opinion, should be done in the near future to overcome the existing barriers in our understanding of this fascinating chemistry that intertwine organic radicals and organometallic complexes.

Background: Diabetes is associated with chronic hyperglycaemia, long-term damage, dysfunction, and organ failure. This study aims to evaluate the antidiabetic activity of the twigs of Andrographis paniculata and its toxicological markers on Streptozotocin (STZ)-induced diabetic Albino rats. Methods: A total of thirty rats were randomly divided into five groups of six animals each. Non-diabetic animals were treated with distilled water as non-diabetic sham control group 1, while diabetic animals (group 2, 3, 4 and 5) were treated with 60 mg/kg bw STZ intravenous (iv) and 100 mg/kg body weight (bwt) of metformin orally for group 2, distilled water for group 3, and 250 and 500 mg/kg bwt of Andrograhis paniculata (A. paniculata) for groups 4 and 5, respectively. The animals were dosed for 28 days, after which they were sacrificed. Liver and kidney function tests as well as livid profile tests were used as the biomarkers of toxicological assessment. Fasting blood glucose was carried out weekly. Oral Glucose Tolerance Test (OGTT) was conducted on the 28th day of the antidiabetic assessment. Results: A. paniculata groups 4 and 5 were significant at different doses (p &lt, 0.05) in reducing the blood glucose level in comparison with metformin. There were significant changes in total and direct bilirubin, total protein, potassium, triglyceride and inorganic phosphorus in 500 mg/kg bwt of the treated group in comparison with the metformin and diabetic group groups. A. paniculata at 500 mg/kg bwt is most effective for its antidiabetic and organ protecting effects.

The correlation relationships between hemostatic potential parameters and concentrations of molecular markers of the hemostasis system: soluble fibrin (sf), D-dimer (DD), fibrinogen (Fg) and protein C (PC) in patients with stenosis of coronary artery 6 months after coronary angioplasty have been investigated. It was found three directions of changes in the state of the patients hemostasis system: an increasing in fibrinolytic activity (C) ~18% of patients; an increasing in coagulative activity (B) ~31% of patients; and maintaining of the balance between coagulation and fibrinolysis (A) ~51% of patients. In patients with signs of stenosis without angina pectoris, a strong Pearson correlation was shown between the half-life of the clot and the overall hemostatic potential (OHP) (r = 0.75, P << 0.05), a moderate relationship between concentrations of sf and D-dimer (r = 0.67, P

One out of eleven adults in the world has diabetes mellitus. 25% of them develop diabetic kidney disease. Thyroid hormones are involved in the regulation of almost all physiological processes in the body, including renal function. The aim of the research was to study the dependance of biochemical markers of renal function in patients with diabetic kidney disease on C/Т polymоrphism in the DIO1 gene. To assess the dependence of biochemical markers of renal function on the C/T polymorphism in the DIO1 gene, the following groups has been formed: 19 patients with CC genotype, 69 individuals – with CT and 14 ones- with TT genotypes. Content of urea and cleatinine in plasma, eGFR, as well as microalbumine and creatinine content in urine were sagnificantly higher in patients with TT genotype than in group of patients with CC genotype and control group (P < 0.05). Presence of the T allele in genotype is associated with violation of thyroid hormones metabolism with the development of nonthyroidal illness syndrome. Carriers of T allele with diabetic kidney disease had significantly worse biochemical indices of renal function, that indicates the dependence of these markers on DIO1 polymorphism.

Green synthesis of different nanoparticles using the plants aqueous extracts has several advantages over other methods due to the environmentally favorable nature of plants. Moreover, such approach is also cost effective. This work describes the biosynthesis of silver nanoparticles (Ag-NPs) with the use of the aqueous extract of dry pericarps of hot chili peppers (Capsicum sp. cv. Teja (S-17) and cv. Carolina Reaper) with different levels of pungency and their antibacterial effect on the antibiotic resistant Pseudomonas aeruginosa. Phytochemical screening of pericarp tissues showed great distinction in contents of phenolic compounds and capsaicinoids as potential reducing agents wich correlated with total antiradical activity as analyzed by reduction of DPPH radicals. The biosynthesized Ag-NPs were characterized by UV-vis spectrophotometry and scanning electron microscopy (SEM). The average size of the nanoparticles in both samples was less than 25 nm. Іnitial concentration of both samples of Ag-NPs inhibited P. aeruginosa growth with equal efficiency.

N-acetyl cysteine (NAC) drug has been used as an antioxidant and anti-inflammatory agent in clinical practice and more recently in the treatment of COVID-19 patients. Using docking analysis and molecular dynamics studies we compare the interaction between of N-acetyl cysteine and its derivatives with SARS-COV-2 main protease (Mpro) which is essential for processing the proteins translated from the viral RNA. The results obtained from this study showed that NAC benzyl ester (NACBn), NAC ethyl ester (NACEt) and NAC amide (NACA) could bind with SARS-COV-2 protease better than NAC drug.

According to modern knowledge, the biological effect of many peptides is mediated by their short-chain fragments – oligopeptides – ranging from 2 to 20 amino acids and the activity of short peptides often significantly exceeds the activity of the peptide precursor. Aim of the review was to summarize the uptodate data on the stability of short peptide sequences, mechanisms of cell penetration, interaction with cell receptors, biological effects and approaches to clinical application. Stability of short peptides is mediated by their structure and molecular weight. Some di-/tripeptides were reported to be able to permeate through intestinal membranes in their intact forms via peptide transporter systems, while others are vulnerable to protease degradation. Although pinocytosis is presumed to be the main mechanism how short peptide sequences enter the cell, some lipophilic oligopeptides were shown to penetrate the cell membrane by the same mechanism as steroid or thyroid hormones and specific extracellular receptors were also described. Low-weighing oligopeptides realize their effect on the cell, chromosomal, genome and molecular levels. The advantages of oligopeptides include oral availability (for low weight compounds), low immunogenicity, high tissue specifici­ty, faster biological effect, better cost efficiency and environmental friendliness of their synthesis. Hence, short peptide sequences are regarded as promising candidates for pharmacotherapy, cell cultures and drug delivery­ purposes.

Zinc (Zn) is involving in the suppressing of inflammation. However, its functionality in the knee joint under the gonarthritis (GA) is not elucidated. The aim of this study was to investigate the participation of Zn-buffering and stress responsive proteins metallothioneins (MTs) in the pathogenesis of the synovial tissues under the experimental acute GA. The inflammation was induced in rats by intra-articular administration of carrageenan. The concentrations of MTs total protein (MTSH), Zn-bound protein (Zn-MTs), total Zn concentration in the tissue, the indexes of oxidative stress and cholinesterase activity were determined. The level of sialic acids was indicated in the blood serum. The enhancing of sialic acids concentration by 42% and cholinesterase depletion confirmed the pathology. In the animals with GA, total level of Zn in the tissue was correspondent to control. However, the MTSH and Zn-MT levels were elevated (by 79 and 46% respectively). This disproportionate rate can be due to partial oxidation of thiols. The superoxide dismutase activity was elevated, radical scavenging activity and protein carbonylation were correspondent to control, but the levels of catalase, glutathione–S-transferase and glutathione were decreased by 28-44%, and lipid peroxidation (TBARS) was increased by 59% compared to control group. Principal Component Analysis confirmed the strong interrelations between MTs and peroxide-related oxidative stress indexes. This preliminary study provides the basis for the understanding of the reason for Zn imbalance in the acute GA as the result of the impairment of thiol redox balance and proposes these biomarkers for the evaluation of knee joint pathologies.

The maintenance of thyroid hormone homeostasis is essential in the regulation of skeletal system development, bone tissue mineralization and fracture risk prevention. This study was carried out to evaluate the serum level of osteoprotegerin (OPG), sclerostin (SOST), and osteocalcin (OC) in hypo- and hyperthyroidism patients. A total number of examined patients was 90 individuals, 30 of them were normal as a control group, the rest 60 individuals were arranged in two groups: 30 patients with hypothyroidism and 30 patients with hyperthyroidism. Serum assay tests for OPG, SOST, OC, thyroid stimulating hormone (TSH), total triiodothyronine (T3), and total thyroxine (T4) were used. The present study reported high levels of SOST, T3, and T4 and low levels of OPG, OC, and TSH in patients with hyperthyroidism compared to control. Whereas in patients with hypothyroidism only SOST and TSH levels were increased, but OPG, OC, T3, and T4 levels were low compared to control. The data obtained indicate the correlation on osteoprotegerin, sclerostin, and osteocalcin levels with thyroid hormones disturbances.

Direct reductive amination of ketones by reductive aminases (RedAms) is a promising method for the synthesis of primary, secondary and tertiary amines. In this work, five naturally occurring RedAms possessing reductive amination activity were identified using a structure-guided genome mining (SGGM) approach, which was based on highly conserved substrate binding and catalysis motif alignment. This RedAm toolbox facilitated the reductive amination of cyclohexanone and 4-fluoropropiophenone with various amine nucleophiles. In a preparative biotransformation (100 ​mg) with low stoichiometric ammonia donor and low catalyst loading, and three types of N-alkylcyclohexylamine were efficiently synthesized with a space-time yield up to 64.2 ​g ​L−1 ​d−1, demonstrating the potential of the RedAm enzymes as a biocatalyst toolbox for the synthesis of primary and secondary amines. Additionally, through protein engineering, the W205F variant of KfRedAm from Kribbella flavida was obtained with a 2-fold increased catalytic efficiency (kcat/Km), and the general applicability of the variant was verified, providing useful guidance for further evolution of RedAms within this family.

Transforming biomass waste into cost-effective catalysts for chemical reactions provides new opportunity for biomass waste valorization. In this work, we examined the possibility of using food waste solid digestate as raw materials for the production of a heterogeneous catalyst for glucose isomerization to fructose, which is one of the important intermediates for the production of platform chemicals, hydrocarbon fuels and synthetic materials from biomass. Hydroxyapatite-based catalysts were obtained from food waste digestate by a coupled hydrothermal-calcination approach. In the hydrothermal treatment process, the addition of exogenous calcium can adjust the alkalinity of the catalyst, which is beneficial to improve the activity of the catalyst. The reaction parameters such as reaction temperature, reaction time and catalyst dosage have also been optimized. The catalyst showed excellent catalytic performance in the glucose isomerization reaction resulting in a high fructose yield of 32.3% with a reaction time of only 20 ​min at 80 ​°C in water. The catalyst can be reused after a simple regeneration without significant activity. This work provides a win-win strategy, which not only solves the problem of the disposal and utilization of digestate, but also expands the synthesis method of the glucose isomerization reaction catalyst.

Herein, we have developed a novel B(C6F5)3-catalysed S–H bond insertion of thiophenols and thiols with α-aryl-α-diazoesters under mild conditions, furnishing various sulfides in moderate to excellent yield. This method features simple operation, mild conditions, broad substrate scope and easy scale-up, which provide an alternative approach for transition-metal catalysed reaction.

A practical and efficient two-step synthetic process for the preparation of (R)-(-)-denopamine has been developed. The key step asymmetric hydrogenation was conducted at mild temperature (60 ​°C) under a hydrogen pressure of 50 ​atm by using Ir/f-amphox as catalyst at low catalyst loading (S/C ​= ​20 ​000). Under the optimized condition, the desired product (R)-(-)-denopamine was obtained with 70% total yield and > 99.9% ee after crystallization. The pilot-scale experiment has been performed at 500 ​g level, showing great potential for the production of high quality active pharmaceutical ingredient (API).

An uncommon aza-Diels-Alder reaction of electron-deficient azoalkenes and electron-deficient 3-phenacylideneoxindoles was successfully developed for convenient construction of the heterocyclic spirooxindoles. The aza-Diels-Alder reaction of azoalkenes, which were in situ generated from base dehydrohalogenation of α-halogeno N-acylhydrazones, with 3-methyleneoxindoles afforded functionalized spiro[indoline-3,3′-pyridazin]-2-ones in good yields and with high diastereoselectivity. Under same reaction conditions, the base promoted reaction of α-halogeno N-acylhydrazones and 3-aryliminoindolin-2-ones in DCM at room temperature resulted in functionalized spiro[indoline-3,3'-[1,2,4]triazin]-2-ones in satisfactory yields.

Made available in DSpace on 2022-04-28T19:47:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background/Aims: Oxidative stress is associated with cardiometabolic alterations, and the involvement of excess glucose and fatty acids has been demonstrated in this process. Thus, the aim of this study was to investigate the effects of different hypercaloric diets on cardiac oxidative stress. Methods: Wistar rats were randomized into four groups: control (C), high-sucrose (HS), high-fat (HF), and high-fat with sucrose (HFS). Nutritional assessment, food profiles, histological analysis, comorbidities, and cardiovascular characteristics were determined. Cardiac oxidative stress was analyzed by malondialdehyde (MDA) and carbonylated proteins, and the cardiac protein expression levels of type 1 angiotensin receptor (AT-1), nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2), superoxide dismutase (SOD 1 e 2), glutathione peroxidase (GPX), and catalase (CAT) were determined by western blot. Results: The HF group showed an increase in adiposity; however, it did not present adipocyte hypertrophy and comorbidities. Cardiac MDA and carbonylated protein levels were higher in the HF and HFS compared with the C group. The levels of oxidant and antioxidant proteins showed no difference between the groups. Conclusion: HF and HFS dietary interventions promoted cardiac oxidative stress, in the presence and absence of obesity, respectively. However, this process was neither mediated by the pro-oxidants AT1 and Nox2, nor by the quantitative reduction of antioxidant enzymes. Postgraduate Program in Nutrition and Health Health Sciences Center Federal University of Espírito Santo, Espírito Santo São Paulo State University (UNESP) Medical School, São Paulo Center for Physical Education and Sports Federal University of Espírito Santo, Espírito Santo São Paulo State University (UNESP) Medical School, São Paulo CNPq: 402090/2016-0

Radical S-adenosylmethionine (radical SAM or rSAM) enzymes use their S-adenosylmethionine cofactor bound to a unique Fe of a [4Fe-4S] cluster to generate the hot 5-deoxyadenosyl radical, which drives highly selective radical reactions via specific interactions with a given rSAM enzymes substrate. This Perspective focuses on the two rSAM enzymes involved in the biosynthesis of the organometallic H-cluster of [FeFe] hydrogenases. We present here a detailed sequential model initiated by HydG, which lyses a tyrosine substrate via a 5-deoxyadenosyl H atom abstraction from those amino acids amino group, initially producing dehydroglycine and an oxidobenzyl radical. In this model, two successive radical cascade reactions lead ultimately to the formation of HydGs product, a mononuclear Fe organometallic complex: [Fe(II)(CN)(CO)2(cysteinate)]-, with the iron originating from a unique dangler Fe coordinated by a cysteine ligand providing a sulfur bridge to another [4Fe-4S] auxiliary cluster in the enzyme. In turn, in this model, [Fe(II)(CN)(CO)2(cysteinate)]- is the substrate for HydE, the second rSAM enzyme in the biosynthetic pathway, which activates this mononuclear organometallic unit for dimerization, forming a [Fe2S2(CO)4(CN)2] precursor to the [2Fe] H component of the H-cluster, requiring only the completion of the bridging azadithiolate (SCH2NHCH2S) ligand. This model is built upon a foundation of data that incorporates cell-free synthesis, isotope sensitive spectroscopies, and the selective use of synthetic complexes substituting for intermediates in the enzymatic assembly line. We discuss controversies pertaining to this model and some remaining open issues to be addressed by future work.

Objectives The aim of the study is to analyze the association of different bitter and sweet gene receptor polymorphisms and bitter and sweet food consumption on formation of dental caries in Turkish adult population. Methods This study included 205 adults whose detailed intraoral health examination was completed and decayed, missing, filled teeth (DMFT) index values were recorded. A mini questionnaire was applied to assess the consumption of bitter and sweet food. A venous blood sample from each participant was collected in Ethylenediamine tetraacetic acid (EDTA) tubes. Further, DNA samples were isolated from the blood samples by utilizing a DNA isolation kit, which were stored at +4 °C prior to the analysis. Taste receptor type 2 member 38 (TAS2R38; rs10246939, rs713598, rs1726866), Taste receptor type 1 member 2 (TAS1R2; rs35874116, rs9701796), and Taste receptor type 1 member 3 (TAS1R3; rs307355) gene polymorphisms were detected using real-time polymerase chain reaction (PCR). Results There was no statistically significant association between the TAS2R38, TAS1R2, and TAS1R3 gene polymorphism and the DMFT index (p>0.05). No significant difference was found between the consumption of bitter and sweet food and the DMFT index (p>0.05). Conclusions TAS2R38 (rs10246939, rs713598, rs1726866), TAS1R2 (rs35874116, rs9701796), and TAS1R3 (rs307355) gene polymorphism may not be associated with the formation of dental caries in the Turkish adult population.

The widespread prevalence of non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), as well as their combination, determines the need for a targeted analysis of this pathology in order to optimize approaches to the diagnosis and treatment of patients with NAFLD and T2DM. As components of the metabolic syndrome, these two diseases have largely similar mechanisms of development and progression, simultaneously increasing the risk of adverse outcomes in comorbid patients. Despite the common pathophysiological mechanisms, the question of the development of NAFLD and T2DM remains significant. Upon conducting literature analysis, two main theories have been identified: alimentary and metabolic. According to the alimentary theory, the primary link in the pathogenesis is obesity and the associated excessive accumulation of free fatty acids and triglycerides in the liver, which subsequently leads to insulin resistance and the development of T2DM. In contrast, the metabolic theory considers diabetes-related insulin resistance as the first hit, which, regardless of obesity, creates preconditions for liver damage. In addition, the review focuses on the consideration of the new concept of Metabolic associated fatty liver disease (MAFLD) as a hepatic manifestation of the metabolic syndrome and considers the clinical phenotypes identified within this pathology. In conclusion, pathogenically based treatment goals in patients with NAFLD and T2DM are overcoming insulin resistance, correcting atherogenic dyslipidemia, and restoring the structures and functions of liver cells.

Background: The use of testosterone replacement therapy (TRT) is widespread. Despite the positive changes, such as: an increase in testosterone levels, an improvement in erectile function and an increase in libido, it is possible to develop a negative manifestation — hyperestrogenism. To date, there are no studies assessing the prevalence of hyperestrogenism in the presence of TRT.Aim: To study the reliability of an increase in total testosterone and estradiol levels and changes in total weight, body mass index (BMI), waist circumference (WC) and hips (OB), depending on the type of TRT and hCG therapy.Materials and methods: For retrospective analysis, the medical records of patients with baseline testosterone deficiency and normal estradiol levels, who were prescribed TRT or hCG therapy, were selected. The patients were divided into 3 groups depending on the form of TRT and hCG therapy. The level of testosterone, estradiol, sex hormone binding globulin (SHBG), weight, OT, OB, BMI in each group was assessed 2 times — before the appointment of treatment and at different periods of treatment, for example, after 3–6–9 and 12 months. Most of the patients had a period of monitoring these parameters before the appointment of TRT or hCG therapy and after 6 months.Results: The increase in the levels of total testosterone and estradiol against the background of TRT in the total sample was 109.6% and 111.3%, respectively. In each group, increases in total testosterone and estradiol levels were significant, p ≤ 0.001. The level of total testosterone to physiological values increased only in the 2-nd group — reaching the average-normal, recommended levels, from 8.7 ± 0.5 (2.5) to 16 ± 2 (10). The maximum rises in total testosterone, as well as estradiol, were noted in the 1st group, from 9.5 ± 0.72 nmol / L (3) to 24.9 ± 2.7 nmol / L (11.62)) and with 24.19 ± 2 (8.5) to 58.1 ± 4 (18.1), respectively. TRT, like hCG therapy, promotes an increase in the level of estradiol, which was demonstrated in all groups, and not only in group 1-st: in group 2-nd from 28.1 ± 2.3 (11.3) to 55 ± 4 (20) and in the 3-rd group from 27.1 ± 2.5 (10.5) to 55.8 ± 4.6 (19.6). On average for the entire sample, from 26.6 ± 1.32 (10.2) to 56.2 ± 2.5 (19). Weight loss on TRT was significant only in the 2-nd group, and in all parameters — weight, BMI, waist and hip circumference. In the 3-rd group, BMI, WC and OB values also slightly decreased. In the 1-st group, the total weight slightly increased, while the BMI did not change, as did the OB value, and the OT value decreased slightly.Conclusion: TRT significantly increases the levels of total testosterone and estradiol, contributing to the normalization of testosterone levels, as in the 2-nd group, or the development of supraphysiological levels of total testosterone and hyperestrogenism, as in the 1st and 3-rd groups. Given that there is a strong belief that TRT leads to significant weight loss, our study confirmed this statement only in the 2-nd group.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases characterized by a defect in one of the enzymes or transport proteins involved in the cortisol synthesis in the adrenal cortex. The most common form of CAH, which occurs in more than 90% of cases, is a 21-hydroxylase enzyme deficiency. The latter is subdivided into nonclassical and classic (salt-losing and virilizing) forms. The prevalence of classic forms of 21-hydroxylase deficiency ranges from 1: 14,000 to 1:18,000 live births worldwide. According to the data of neonatal screening in the Russian Federation, the prevalence of the disease in some regions ranges from 1: 5000 to 1: 12000, in the country as a whole - 1: 9638 live newborns. The non-classical form of CAH occurs more often - from 1: 500 to 1: 1000 among the general population. In second place is the hypertensive form of CAH - a deficiency of 11β-hydroxylase, which, according to the literature, occurs in about 1 per 100,000 newborns. These clinical guidelines were compiled by a professional community of narrow specialists, approved by the expert council of the Ministry of Health of the Russian Federation, and updated the previous version published in 2016. The clinical guidelines are based on systematic reviews, meta-analyses and original articles, and scientific work on this issue in the Russian Federation and other countries. The purpose of this document is to provide clinicians with the most up-to-date, evidence-based guidelines for the CAH diagnosis and treatment

Some environmental chemicals capable of interfering with the endocrine regulation of energy metabolism and the structure of adipose tissue in the function of the reproductive, immune, cardiovascular and other systems are called endocrine disruptors or disruptors. According to the WHO definition, the term «endocrine disruptors» means: «Exogenous substances or mixtures thereof that alter the function (s) of the endocrine system and, as a result, cause adverse effects in the intact organism or in its offspring, or (sub) population.» This includes compounds to which humanity is exposed in daily life as a result of their use in pesticides, herbicides, industrial and household products, plastics, detergents, refractory impregnations and as ingredients in personal care products. This review will present the latest scientific data on various ERs, such as persistent organic pollutants (POPs): pesticides (mirex, chlordecane, endosulfan, hexachlorobenzene-HCB dichlorodiphenyltrichloroethane-DDT and its metabolites), industrial chemicals (bisphenol A, polybrominated ether -PBDE, polychlorinated biphenyls-PCB, nonylphenol, dioxins, perfluorooctanoic acid-PFOA, phthalates), pharmaceuticals (diethylstilbestrol-DES). ERs are regarded as compounds that cause obesity, since they have the ability to influence cellular processes associated with adipose tissue, initiating changes in lipid metabolism and adipogenesis. Analysis of scientific materials on this issue indicates that ERs are ubiquitous in the environment and have a detrimental effect on the health of animals and mankind. The scientific and practical interest in this article is based on the growing statistics of the development of such socially significant pathologies as obesity and related diseases, including diabetes mellitus, metabolic syndrome, cardiovascular diseases, menstrual irregularities, as well as cancer and infertility, for of which obesity is a risk factor.

Background: Considering the influence of visceral obesity on male infertility, the investigation of ejaculate quality indicators under obesity treatment is relevant.Objective: Evaluation of ejaculate quality indicators by obesity treatment with liraglutide in andrologically healthy men with infertility and post-pubertal visceral obesity.Methods: Infertile men with post-pubertal alimentary visceral obesity were included in a pilot observational prospective study. All patients were given recommendations for body weight loss (hypocaloric diet, daily aerobic physical activity) as well as an average daily dose of liraglutide 2.4 [2.4; 3.0] mg. Evaluation of waist circumference, antioxidant activity of ejaculate, spermogram was carried out initially and after 6 months. The differences were considered statistically significant at p Results: The body weight decrease was -11.7 [12.4; 11.0]%, the waist circumference decrease was 8 [12; 7] cm. In dynamics, increased content of living sperm in ejaculate from 92 [90; 95]% to 95 [92; 98]%, morphologically normal forms from 5 [3; 6]% to 6 [3; 8]%, mobility of A + B from 25 [15; 36] to 35 [19; 52]%, seminal antioxidant capacity, a decrease in reactive oxygen forms in the neat ejaculate were statistically significant. Increasing the sperm count in 1 ml and decreasing reactive oxygen forms in the washed ejaculate did not reach statistical significance.Conclusion: Ejaculate quality indicators improved by the complex obesity therapy with liraglutide in young andrologically healthy men with postpubertal visceral obesity.

Idiopathic hypoparathyroidism is a rare endocrine disease diagnosed when all possible causes of hypoparathyroidism are excluded.Data on the prevalence of idiopathic hypoparathyroidism is limited, there are several local studies in some countries. The variety and non-specificity of the hypoparathyroidism symptoms, similarity to other diseases (eg. epilepsy), causes the misdiagnosis and delay in pathogenetic therapy.Idiopathic hypoparathyroidism is rare. Therefore, the absence of neck surgery in the anamnesis practically excludes hypoparathyroidism from the diagnostic search. Moreover, it is necessary to rule out all known causes of decreased PTH hypoparathyroidism to determine the form of non-surgical hypoparathyroidism.We present a case series of idiopathic hypoparathyroidism, which demonstrates the difficulty in diagnosis, and the clinical features of the disease. The article covers also the problem of modern diagnostic approaches including the determination of the interferon-omega for patients with suspected autoimmune polyglandular syndrome type 1 as the most common cause of nonsurgical hypoparathyroidism.

The prevalence of metabolic syndrome (MS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnostics and approaches to the prevention and treatment of this pathology. Age, lifestyle, socioeconomic status, insulin resistance (IR), dyslipidemia, obesity and genetic predisposition are factors influencing the risk of developing and progression of MS. Features of the distribution and dysfunction of adipose tissue are important factors in the development of IR, with obesity, as well as the risk of the formation of cardiometabolic diseases and MS. ­Understanding of mechanisms is linked to advances in metabolic phenotyping. Metabolic phenotyping of obese persons is important for the development of important diseases in relation to the study of the pathophysiology of metabolic disorders, the possible concomitant disease and the search for innovative strategies for the prevention and treatment of MS. The understanding of MS mechanisms is associated with advances in metabolic phenotyping. Therefore, the relevance of further study of the pathophysiological mechanisms underlying various metabolic phenotypes of MS is one of the promising areas of modern scientific research. This review summarizes the current literature data on the prevalence of MS depending on gender, age, population, area of residence, education, level of physical activity, and many other parameters. Metabolic risks of MS development are detailed. Biological markers of MS are considered. The necessity of metabolic phenotyping of MS has been shown, which may have potential therapeutic value.

BACKGROUND/AIMS: The osmolytes involved in the volume regulation of hyposmotically-swollen fish cells are well identified. However, if a coordination and adjustments of their fluxes are obvious, few studies have clearly illustrated these aspects. METHODS: Trout red blood cells volume variations were estimated from water contents obtained by a gravimetric method. Intracellular K+ and Na+ contents, and Cl- content of haemolysed cells were determined by photometry and colorimetry, respectively. The taurine contribution to cell volume regulation was calculated from the net changes of water, K+, Cl- and Na+ contents. The intracellular pH was calculated from the chloride distribution across the cells membranes according to the Donnan equilibrium. RESULTS: Cells responses to a rapid change (from 296 to 176 mOsm.kg-1) of the saline osmolality were examined in three conditions designed to not impact (Hypo. I) or to reduce the K+ (Hypo. II) and Cl- (Hypo. III) contributions to the volume regulation. Hypo. I condition caused an immediate increase in water content, followed by a 90 min. full regulation, concomitant with gradual lowering of K+ and Cl- contents and a surprising increase in Na+ content. Hypo. II and III conditions showed a partial and complete volume regulation, respectively. This was made possible by an increase in the taurine involvement. These experiments allowed to confirm that K+ and Cl- were released via KCl cotransport and by separate channels. The comparison of Hypo. I and III conditions led to the observation that the partially amiloride-sensitive Na+ influx is proportional to the taurine efflux; the latter being sustained mainly by a Na+/taurine cotransport. The Hypo. II condition was suitable for the (Na+/K+)ATPase activity inhibition. This effect could explain the observed lack of Na+ uptake, the consecutive depletion of intracellular taurine stock and the incomplete volume regulation. Finally, the results support the importance of taurine in pH control under Hypo. I (physiologic) condition. The alkalosis observed in Hypo. II and III conditions were the consequences of changes in the salines compositions, not of physiologic adjustments. CONCLUSION: The regulatory volume decrease process of trout RBCs is complex and adjustable through coordinated osmolytes movements. The obliged decrease in K+ and/or Cl- contributions stimulates taurine and Na+ pathways. This study highlights the importance of taurine as a compensatory variable in cell volume regulation and explains for the first time the significance of the Na+ uptake during this process

Background/aims Binding of histones to molecular pattern recognition receptors on endothelial cells and leukocytes provokes proinflammatory responses and promotes activation of coagulation. Histones also bind therapeutic heparins, thereby neutralizing their anticoagulant functions. The aim of this study was to test the hypothesis that histones can interact with the antithrombin (AT)-binding vascular glycosaminoglycans (GAGs) to induce inflammation and inhibit the anti-inflammatory function of AT. Methods We evaluated the heparin-binding function of histones by an AT-dependent protease-inhibition assay. Furthermore, we treated endothelial cells with histones in the absence and presence of AT and monitored cellular phenotypes employing established signaling assays. Results Histones neutralized AT-dependent anticoagulant function of heparin in both purified protease-inhibition and plasma-based assays. Histones also disrupted endothelial cell barrier-permeability function by a GAG-dependent mechanism as evidenced by the GAG-antagonist, surfen, abrogating their disruptive effects. Further studies revealed histones and AT compete for overlapping binding-sites on GAGs, thus increasing concentrations of one protein abrogated effects of the other. Histones elicited proapoptotic effects by inducing nuclear localization of PKC-δ in endothelial cells and barrier-disruptive effects by destabilizing VE-cadherin, which were inhibited by AT, but not by a D-helix mutant of AT incapable of interacting with GAGs. Finally, histones induced release of Weibel-Palade body contents, VWF and angiopoietin-2, and promoted expression of cell adhesion molecules on endothelial cells, which were all downregulated by AT but not by D-helix mutant of AT. Conclusion We conclude that histones and AT compete for overlapping binding sites on vascular GAGs to modulate coagulation and inflammation.

The performance of CoCrMo alloy in orthopaedic implants may be unfavourably affected by hyaluronic acid (HA) in synovial fluid. In this study, the authors aimed to understand the interactions between HA and CoCrMo using dedicated electrochemical experiments and surface analyses. A sequence of electrochemical measurements (open‐circuit potential, linear polarization resistance, potentiodynamic and potentiostatic polarizations) was run on LC‐CoCrMo (ASTM F1537) in Dulbecco's phosphate‐buffered saline (DPBS) solution with and without HA and in DPBS mixed with newborn calf serum (NCS) and HA, partially under simultaneous recording of surface pH using custom‐made microelectrodes. Samples were analysed by optical and electron microscopy. HA had no significant impact on the corrosion potential of CoCrMo alloy (ECORR = −173 ± 8, −211 ± 16, and −254 ± 30 mVAg/AgCl, in DPBS, DPBS + HA, and DPBS + NCS + HA, respectively). Average current density values at the transpassive domain were double in DPBS compared to DPBS + HA and DPBS + NCS + HA. At potentials above +0.6 VAg/AgCl, surface pH values decreased from 7.5 to 6.5 in DPBS and from 7.5 to below 4 in DPBS + HA. In conclusion, the presence of HA did not compromise the corrosion resistance of CoCrMo alloy at free potential, but it enhanced acidic conditions at the near surface under anodic‐applied potential in the transpassive domain.

The cationic polymerization of isobutylene and its block copolymerization with styrene using DiCumCl/TiCl4/2,6-lutidine initiating system has been studied in open conditions. It was shown that a higher concentration of proton trap is required in open conditions as compared to the glove box technique in order to have good control over molecular weight and polydispersity. Polyisobutylenes with Mn ≤ 50,000 g mol−1 and low polydispersity (Đ ≤ 1.2) were prepared at [Lu] = 12 mM. The synthesis of poly(styrene-block-isobutylene-block-styrene) triblock copolymer (SIBS) in open conditions required the addition of proton trap into two steps, half at the beginning of the reaction and the second half together with styrene. Following this protocol, a series of triblock copolymers with different length of central polyisobutylene block (from Mn = 20,000 g mol−1 to 50,000 g mol−1) and side polystyrene blocks (Mn = 4000 g mol−1–9000 g mol−1) with low polydispersity (Đ ≤ 1.25) were synthesized. High molecular SIBS (Mn &gt, 50,000 g mol−1) with low polydispersity (Đ &lt, 1.3) containing longer polystyrene blocks (Mn &gt, 6000 g mol−1) demonstrated higher tensile strength (~13.5 MPa).

Edible insects have gained attention due to their impressive nutritional composition, as well as their efficient use of natural resources. However, a research gap remains on the applications of insect chitosan, especially as it relates to their potential use as food packaging material. Chitosan from two reared cricket species (Acheta domesticus and Gryllodes sigillatus) was evaluated for use as food packaging material. Cricket chitosan films (CCF) were structurally similar to commercial shrimp chitosan films (SCF) at controlled glycerol levels, as seen by shared spectral peaks in FT-IR analyses. Mechanical properties of CCF showed they had equal or greater tensile strength when compared to commercial SCF, although flexibility was lower. Scanning electron microscopy showed increased roughness of microstructure, likely increasing the tortuosity. As a result, CCF had improved water vapor permeability compared to commercial SCF. Melanin complexes present in cricket chitin and chitosan increased hydrophobicity and decreased light transmittance. This study also revealed that intrinsic species differences, which occur during insect and crustacean exoskeleton development, could have effects on the functionality of chitosan packaging materials. Overall, CCF were found to be as effective as commercial SCF, while providing additional advantages. CCF derived from reared crickets have good mechanical and barrier properties, and improved water resistance and light barrier characteristics. Edible cricket chitosan has the potential to be used as bio-based packaging material for food and pharmaceutical applications.

Background. The ultimate goal of the study was to approximate the burden and patterns of dyslipidemia in a subset of the elderly population (≥60–85 years) living in Asmara, Eritrea, and to identify modifiable risk drivers. Methods. A total of 319 (145 (45.5%) male vs. 174 (54.5%) female, mean age ± SD (68.06 ± 6.16 years), participants from randomly selected estates within Asmara were enrolled. Demographic and medical information was collected using a standardized questionnaire. Anthropometric, lipid panel, fasting plasma glucose (FPG), and blood pressure (BP) measurements were subsequently taken. Results. The prevalence of dyslipidemia was 70.5%. The proportions of dyslipidemias were (in order of decreasing frequency) high TC (51.2%), LDL-C (43.7%), low HDL-C (28.2%), and TG (27.6%). The average (±SD) concentrations in mg/dL of TC, LDL-C, non-HDL-C, TG, HDL-C, TC/HDL-C, and TG/HDL-C were 202.2 ± 40.63 , 125.95 ± 33.16 , 151.72 ± 37.19 , 129 ± 57.16 , 50.48 ± 10.91 , 4.11 ± 0.91 , and 2.72 ± 1.49 , respectively. Furthermore, 17.5%, 21.6%, 11.0%, and 5.0% had abnormalities in 1, 2, 3, and 4 lipid disorders with the copresence of TC+LDL-C abnormalities dominating. Regarding National Cholesterol Education Program Third Adult Treatment Panel risk strata, 18.5%, 14.5%, 28.2%, and 12.9% were in high or very high-risk categories for TC, LDL-C, TG, and HDL-C, respectively. The high burden of dyslipidemia coexisted with an equally high burden of abdominal obesity (43.1%), FPG ≥ 100 mg / dL (16%), hypertension (28.5%), and physical inactivity. Overall, dyslipidemia was associated with sex (females: aOR = 2.6 , 95 % CI = 1.1 – 6.1 , p = 0.017 ) and daily physical activity—higher in individuals undertaking physical activity for aOR = 2.6 , 95 % CI = 1.1 – 6.1 , p = 0.029 ), 1-2 hours ( aOR = 3.2 , 95 % CI = 1.24 – 8.5 , p = 0.016 ), and 2-3 hours ( aOR = 2.0 , 95 % CI = 0.7 – 5.8 , p = 0.192 ) (Ref: >3 hours). Additional associations included increasing FPG ( aOR = 1.02 , 95 % CI = 1.0 – 1.04 , p = 0.039 ), and BMI ( aOR = 1.19 , 95 % CI = 1.09 – 1.3 , p < 0.001 ). These factors, along with waist circumference (WC), consumption of traditional foods, systolic BP, and diastolic BP, were, with some variations, associated with disparate dyslipidemias. Conclusions. The burden of dyslipidemia in the elderly population in Asmara is high. Modifiable risk drivers included FPG, WC, physical inactivity, and low consumption of traditional food. Overall, efforts directed at scaling up early recognition and treatment, including optimal pharmacological and nonpharmacological therapy, at all levels of care, should be instituted.