Dendrimer Platforms for Targeted Doxorubicin Delivery-Physicochemical Properties in Context of Biological Responses.

The unique structure of G4.0 PAMAM dendrimers allows a drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin hydrochloride (DOX) were optimized. The physicochemical properties of the system were monitored using dynamic light scattering (DLS), circular dichroism (CD), and fluorescence spectroscopy. The Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier's surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the Isothermal calorimetry (ITC) isotherm. Fluorescence spectra and release curves identified the reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of the G4.0-DOX complex was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is essential from a therapeutic point of view.

Two-step conversion of uridine and cytidine to variously C5-C functionalized analogs.

C5-substituted pyrimidine nucleosides are an important class of molecules that have practical use as biological probes and pharmaceuticals. Herein we report an operationally simple protocol for C5-functionalization of uridine and cytidine via transformation of underexploited 5-trifluoromethyluridine or 5-trifluoromethylcytidine, respectively. The unique reactivity of the CF3 group in the aromatic ring allowed the direct incorporation of several distinct C5-C "carbon substituents": carboxyl, nitrile, ester, amide, and amidine.

Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study.

In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According to the results, all the tested compounds exhibited inhibitory activity on the proliferation of all lines of cancer cells (colon adenocarcinoma (LoVo), resistant colon adenocarcinoma (LoVo/DX), breast cancer (MCF-7), lung cancer (A549), cervical cancer (HeLa), human leukemic lymphoblasts (CCRF-CEM) and human monocytic (THP-1)). In particular, their feature stronger influence on the activity of P-glycoprotein of cell cultures resistant to doxorubicin than doxorubicin. Tested compounds have more lipophilic character than doxorubicin, which determines their affinity for the molecular target and passive transport through biological membranes. Moreover, the inhibitory potential against topoisomerase II and DNA intercalating properties of synthesized compounds were analyzed via molecular docking.

Reconstructing GRACE-type time-variable gravity from the Swarm satellites.

The Gravity Recovery and Climate Experiment (GRACE) mission has enabled mass changes and transports in the hydrosphere, cryosphere and oceans to be quantified with unprecedented resolution. However, while this legacy is currently being continued with the GRACE Follow-On (GRACE-FO) mission there is a gap of 11 months between the end of GRACE and the start of GRACE-FO which must be addressed. Here we bridge the gap by combining time-variable, low-resolution gravity models derived from European Space Agency's Swarm satellites with the dominating spatial modes of mass variability obtained from GRACE. We show that the noise inherent in unconstrained Swarm gravity solutions is greatly reduced, that basin averages can have root mean square errors reduced to the order of [Formula: see text] of equivalent water height, and that useful information can be retrieved for basins as small as [Formula: see text]. It is found that Swarm data contains sufficient information to inform the leading three global mass modes found in GRACE at the least. By comparing monthly reconstructed maps to GRACE data from December 2013 to June 2017, we suggest the uncertainty of these maps to be [Formula: see text] of equivalent water height.

The Potential Antimicrobial Action of Human Mucin 7 15-Mer Peptide and Its Metal Complexes.

Mucin 7 (encoded byMUC7) is a human salivary protein that has a role in the natural immune system. Fragments of mucin 7 exhibit antimicrobial activity against bacteria and yeast. Although the antimicrobial properties of peptides have been known and studied for decades, the exact mechanism of action of antimicrobial peptides (AMPs) is still unclear. It is known that some AMPs require divalent metal ions to activate their activity. Herein, we investigated three 15-mer MUC7 peptides, one of which (mother peptide, sequence, L3) is a synthetic analog of a fragment naturally excised from MUC7 (with His3, His8, and His 14) and its two structural analogs, containing only two histidine residues, His3, His13 and His8, His13 (L2 and L1, respectively). Since there is a correlation between lipophilicity, the presence of metal ions (such as Cu(II) and Zn(II)) and antimicrobial activity of AMP, antimicrobial properties of the studied peptides, as well as their complexes with Cu(II) and Zn(II) ions, were tested for activity against Gram-positive (Enterococcus faecalis, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans). The results were correlated with their lipophilicity. Coordination and thermodynamic studies (potentiometry, UV-Vis, CD) revealed the formation of mainly mononuclear complexes in solution for all studied systems with different stability in the physiological pH range.

Functional anatomy, histology and biomechanics of the human Achilles tendon - A comprehensive review.

OBJECTIVES: The aim of this study was to provide a comprehensive overview of the anatomical, histological, and biomechanical aspects of the Achilles tendon. METHODS: A comprehensive search on the relevant aspects of the Achilles tendon was performed through the main electronic databases up to October 2019. Data from relevant articles was gathered, analyzed, and included in this review. RESULTS: This review outlines crucial topics on the anatomy, histology, and biomechanics of the Achilles tendon. The first part, focusing on clinically relevant anatomy, describes the tendon as well as its surrounding structures. Particular focus is made on anatomical divisions. The second part discusses histologic features, contrasting normal morphology with pathologic changes. The third part summarizes various biomechanical aspects of the Achilles tendon, especially those crucial to understanding the key functionality of the tendon. These components make up this review aimed to aggregate relevant information regarding the Achilles tendon to provide an up to date assessment of current knowledge, as well as visions for future directions of Achilles tendon research. CONCLUSIONS: Comprehensive knowledge regarding the Achilles tendon is crucial whilst rates of injury continue to be relevant. A proper understanding of the anatomy, histology, and biomechanics is vital for clinical perception as well as establishing the direction of further research in new therapies.

Human salivary MUC7 mucin fragment and its analogues. Coordination and biological studies.

Mucin 7 (called MUC7 or MG2) is a salivary protein whose fragments exhibit a strong antimicrobial activity and is a natural protection of organisms against pathogens. Up to date however the exact mechanism of their actions is unknown. One hypothesis covers an involvement of biologically occurring metal ions in this process. Herein, three 12-mer peptides have been included in the study, one of which (mother-peptide sequence, L3) is a direct analogue of a fragment naturally cut out from the MUC7 (with His3 and His8) and its two structural analogues, containing only one histidine residues His3 or His8 (L2 and L1, respectively), which are essential for binding to metal ions. Antimicrobial properties of the studied peptides as well as their complexes have been tested against bacterial and fungal strains revealing activity towards Gramm-positive bacteria (Enterococcus faecalis and Staphylococcus epidermidis) which were slightly enhanced upon Cu(II) or Zn(II) ions coordination. The study of both the biological and thermodynamic properties of considered systems has not been measured before. Exact coordination studies (potentiometry, ultraviolet/visible spectroscopy - UV-Vis, circular dichroism spectroscopy - CD) revealed the formation of mainly mono-nuclear complexes in solution for all studied systems in which the binding abilities turned out to be inversely proportional to the antimicrobial properties exhibited. However, distinctly different lipophilicity of peptides, the reduction of which (also upon metal coordination) increases the ability to inhibit the growth of E. faecalis and S. epidermidis strains, seems to be the most important factor of their activity.

An assessment of energy expenditure of soldiers serving in the Polish chemical units, performing training tasks in 2 types of personal chemical protective clothing - comparative studies.

OBJECTIVES: Individual protection against contamination is the kind of protection provided to persons in an environment contaminated with radioactive substances, and war toxic or biological agents, including the use of gas masks, and insulating or filtration skin protection agents. The aim of this work was to perform a comparative assessment of energy expenditure of chemical troop soldiers wearing L-2 insulating personal protective clothes (PPC) and FOO-1 filter-sorptive PPC during training in the training ground conditions. Surveys on the subjective assessment of comfort related to using the L-2 and FOO-1 PPC were carried out as well. MATERIAL AND METHODS: A total of 29 men doing the same training tasks, wearing the L-2 PPC and FOO-1 filter-sorptive protective clothing with an MP-5 filter gas mask, underwent the examination. Measurements of energy expenditure values were done based on the frequency of heart contractions, recorded by the Polar Sport Tester 810 heart rate monitor. RESULTS: It was found that an average energy expenditure of soldiers, resulting from performing training tasks, was lower among the subjects wearing the FOO- 1 filter-sorptive PPC, compared to the energy load of the ones using the L-2 PPC. CONCLUSIONS: According to Christensen's classification of work severity, the average energy expenditure makes it possible to qualify works performed by soldiers using both types of PPC to moderate work. In the opinion of the examined soldiers serving in the chemical troops, the FOO-1 filter-sorptive PPC increases the sense of security while on a threatened ground. The FOO-1 filter-sorptive PPC is assessed by chemical troop soldiers as better because it hinders tasks fulfillment to a lesser extent. Int J Occup Med Environ Health. 2019;32(5):645-52.

TIMP-1 association with collagen type I overproduction in hereditary gingival fibromatosis.

OBJECTIVES: To investigate the processes associated with the excessive production of collagen I in hereditary gingival fibromatosis (HGF). MATERIALS AND METHODS: Three HGF subjects and five controls were enrolled in the study. Histomorphological and immunohistological analyses were performed on gingival tissues. The expression of heat-shock protein 47 (HSP47), collagen I, transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) by gingival fibroblasts isolated from HGF and controls was analysed using qRT-PCR, Western blotting and ELISA. RESULTS: Considerable accumulation of fibrotic fibrils and increased synthesis of HSP47 were noted in HGF gingival tissues. The synthesis of collagen I, HSP47, TGF-ß1, CTGF and TIMP-1 was significantly elevated in HGF gingival fibroblasts compared with controls, while the production of MMP-1 was decreased. CONCLUSIONS: We report that fibrosis in HGF gingival tissues is associated with increased synthesis of HSP47. This finding was confirmed by an in vitro study, where excessive production of collagen I was associated with increased synthesis of HSP47, TGF-ß1 and CTGF by HGF gingival fibroblasts. Moreover, the shift in the TIMP-1/MMP-1 ratio identifies increased synthesis of TIMP-1 as one of the processes associated with collagen I overproduction in HGF fibroblasts.

Effect of 3-year education in the Main Fire Service School on the fitness level of students.

INTRODUCTION AND OBJECTIVE: The aim of the study was to determine changes in the fitness level among students of the Main Fire Service School during 3-year's education. MATERIAL AND METHODS: A total of 75 male and 5 female students took part in the study. Fitness level measurements were carried out before beginning the studies (Measurement 0) and after the 1st, 2nd and 3rd years at the school (Measurement 1, 2, 3). The following tests were performed to estimate level of physical fitness for men: pull-ups on a bar, a 50 m sprint and 1,000 m run, and for women: sit-ups, medical ball (2 kg) throw from above the head and a 4 x10 m shuttle run. RESULTS: General fitness level (average number of points from 3 attempts) of the male and female students improved. Improvement of fitness level between Measurement 0 (male students 60.3p.±7.58; female students 61.60p.±3.08), and Measurements 1, 2, 3 (men 64.59p.±6.87; 64.41p.±7.17; 64.03p.±7.65 and women 68.40p.±1.99; 66.67p.±2.36; 68.87±1.87 respectively), was found. The same relationship was found while analysing results of individual competitions. Only speed endurance (anaerobic-aerobic) assessed during Measurement 0 at 64.03p.±10.23, decreased after the 1st year at the school (Measurement 1 - 59.29p.±14.14) and remained on the same level during Measurements 2 and 3 (60.25p.±11.20 and 58.56p. ±12.80, respectively). CONCLUSIONS: Speed endurance (anaerobic-aerobic) is a capability which decreased among the students in the subsequent years. Because this capability highly correlates with activities that a fire-fighter will perform during rescue operations, it should be treated as a matter of priority during physical education classes in the Main Fire Service School.

Influence of protein deficient diet, vitamin B[sub]2[/sub] supplementation and physical training on serum composition of polyunsaturated fatty acids (PUFAs) in rats.

[b]Introduction[/b]. Prolonged shortages of protein in the diet significantly alter the composition and content of polyunsaturated fatty acids (PUFA) in tissues and body fluids. One of nutritional factors which may reduce negative effects of protein malnutrition might be vitamin B[sub]2[/sub] due to its influence on lipids metabolism. [b]Objective. [/b]The aim of the study was to investigate the influence of low protein (LP) diet enriched with vitamin B[sub]2[/sub] on the content and composition of PUFA in the blood serum of rats treated with dosed physical exercise. [b]Materials and method. [/b]The experiment was carried out for 3 months on 72 growing male Wistar rats divided into 5 groups. Animals were fed ad libitum on a diet with an energy value of 350 kcal/100 g, in which 4.5% of the energy was provided by protein. In the control diet, 20% of the energy was provided by protein. Two groups were fed the diet enriched with vitamin B2. The two groups of tested animals were trained for 5 days a week. [b]Results.[/b] LP diet caused a decrease in α-linolenic acid (ALA) after 30 days, and a decrease in docosahexaenoic acid (DHA) after 60 days of experiment, compared with rats fed the control diet. After 60 and 90 days of the experiment, a significant decrease was noted in arachidonic acid (AA) in serum of trained rats, compared with sedentary rats fed the LP diet. Physical activity increased LA (mainly on day 30), EPA (on day 90) and reduced AA content (on day 90) in serum of rats fed the LP diet. B2 supplementation in the trained LP group did not change the EPA and AA dependence; however, there was a decrease in LA content in comparison to the non-supplemented trained group. [b]Conclusions. [/b] Results of this study suggest that all investigated factors (protein deficiency, physical exercise and supplementation of vitamin B2) have significant impact on PUFA composition of serum in rats.

Influence of Military Training and Standardized Nutrition in Military Unit on Soldiers' Nutritional Status and Physical Fitness.

Tomczak, A, Bertrandt, J, Klos, A, and Klos, K. Influence of military training and standardized nutrition in military unit on soldiers' nutritional status and physical fitness. J Strength Cond Res 30(10): 2774-2780, 2016-Despite suspension of conscription in Polish Army, trainings of soldiers are still carried out. It is expected that they will be effective and will contribute to obtaining optimum level of psychophysical efficiency that enables fulfillment of military tasks. Total of 60 soldiers took part in the study. During the 9-month military service, soldiers had 200 hours of physical training and basic military training (shooting, drill, anti-chemical training, topography, general tactics, and military equipment operation). The training lasted 8 hours everyday. To assess fitness level, 4 trials were done: long jump, pull-ups, sit-ups, and 1,000 m run. Evaluation of food was based on the analysis of full board menus using the "Tables of composition and nutritional value of food products." Energy value was assessed, and content of basic nutrients was calculated. Assessment of nutritional status was based on anthropometric measurements, such as body height, body mass, and thickness of 4 selected skinfolds. Body height and body mass were the basis for the body mass index calculation. Soldiers serving in the mechanized infantry unit, after completing the training, got better results only in 1,000 m run (from 250.3 to 233.61 seconds). During the research, an average energy value of a daily food ration planned for consumption was 4,504 kcal. This value consisted of 13.2% of energy from protein, 31.9% of energy from fat, and 54.9% from carbohydrates. In the course of military service, percentage of subjects indicating overweight increased from 10.2 to 25.4%.

The influence of vitamin B12 supplementation on the level of white blood cells and lymphocytes phenotype in rats fed a low-protein diet.

Protein malnutrition has a negative effect on body composition and some blood parameters, especially in the young growing organism. One of nutritional factors which could protect against negative consequences of protein deficiency may be B group vitamins. The aim of the study was to investigate the effect of vitamin B12 supplementation on the immune system in rats fed a standard and a low-protein diet. Rats were fed a control (20% of energy from protein) or a protein-deficient diet (4.5% of energy from protein). Half of animals in each group were additionally supplemented with vitamin B12 (300% of the daily intake). The white blood cells analysis and lymphocytes immunophenotyping (number and percentage) were performed. Low-protein diets caused disturbances in WBC and lymphocyte subpopulations in both short- (30-day) as well as long-term periods (90-day). Vitamin B12 supplementation significantly reduced the negative impact of protein malnutrition after 30 days, however had no effect on long-term malnutrition. Furthermore, vitamin B12 addition in rats fed a control diet did not affect the studied parameters. This observation opens the promise of use of vitamin B12 supplementation to improve immune system parameters in protein malnourished organisms.

The unusual stabilization of the Ni2+ and Cu2+ complexes with NSFRY.

The binding mode provided by an unprotected peptide with non-coordinating side-chains is simple and well understood. However, when particular residues are inserted into the peptide sequence, they can have a significant impact on the stability of the formed complexes. The presence of non-bonding side chains of amino acids close to the metal binding centre in the peptide/protein can provide special interactions which result in increasing the stabilization of the formed species. Moreover, these interactions can play a crucial role in generating particular protein structures and in influencing biological activity. In the present paper it is shown how peptides with no specific predisposition for metal binding, like ANF peptides, can form metal complexes with a very high thermodynamic stability. For better understanding this peculiar behavior, a combined pH-metric and spectroscopic method was used to determine the stability and the solution structure of Cu(2+) and Ni(2+) complexes with NSFRY-NH(2) (ANF peptide) and a series of analogue peptides. All obtained data support the hypothesis that the complex-formation process is very similar for both metal ions and all the ligands, involving some intramolecular interactions among the different side chains. The two-dimensional NMR analysis of nickel complexes showed the occurrence of many inter-residue correlations and suggested the presence of a direct interaction between the d electrons of the metal ion and the π-ring system of the aromatic side-chains of the ligand.

[Dressler syndrome following pulmonary embolism]. / Zespól Dresslera po zatorowosci plucnej.

A case of a 73-year-old woman with fibrinous pericardial effusion which developed four weeks following severe pulmonary embolism. Clinical and echocardiographic data as well as an inclination to self-limited course were suggestive of Dressler syndrome diagnosis. Although there were no data that oral vitamin K antagonist use was involved in presented pericardial syndrome, pericardial effusion size required its temporary substitution by heparin.

Zn(II) ions bind very efficiently to tandem repeat region of "prion related protein" (PrP-rel-2) of zebra-fish. MS and potentiometric evidence.

Multi-histidine peptide fragments of zebra-fish prion protein are effective ligands for Zn(II) ions. Moreover the formation of a dinuclear complex species with a longer peptide can suggest the existence of the cooperative effect in the metal ion binding.

NMR studies of the Zn2+ interactions with rat and human beta-amyloid (1-28) peptides in water-micelle environment.

Alzheimer's disease is a fatal neurodegenerative disorder involving the abnormal accumulation and deposition of peptides (amyloid-beta, Abeta) derived from the amyloid precursor protein. Here, we present the structure and the Zn2+ binding sites of human and rat Abeta(1-28) fragments in water/sodium dodecyl sulfate (SDS) micelles by using 1H NMR spectroscopy. The chemical shift variations measured after Zn2+ addition at T>310 K allowed us to assign the binding donor atoms in both rat and human zinc complexes. The Asp-1 amine, His-6 Ndelta, Glu-11 COO-, and His-13 Nepsilon of rat Abeta28 all enter the metal coordination sphere, while His-6 Ndelta, His-13, His-14 Nepsilon, Asp-1 amine, and/or Glu-11 COO- are all bound to Zn2+ in the case of human Abeta28. Finally, a comparison between the rat and human binding abilities was discussed.

[The assessment of nutritional status of the selected navy warship crew]. / Antropometryczna ocena stanu odzywienia zalogi wybranej jednostki plywajacej marynarki wojennej.

The aim of the work was the assessment of nutritional status of the ORP "PULASKI" frigate crew before long lasting training cruise. Crew of the warship consisting of 156 men, aged 22-42, underwent the nutritional status examination. The nutritional status was estimated based on the anthropometrical measurements. Body mass and body height of examined men was the base to calculate the Body Mass Index (BMI). Based on this index, using the Ferro-Luzzi classification, examined soldiers were classified into groups indicating overweight or obesity. It was observed that percentage of persons indicating overweight increased with the age. Overweight was found among 49% of examined aged up to 30, 54.3% of men aged up to 40 indicated overweight. Obesity was found among 13.5% of examined sailors aged up to 30 and among 10.9% sailors aged 40. Obesity found among sailors creates necessity to carry on large-scale prophylaxis operations including propagation of rational nutrition and healthy life style education.

Ephedrine-caffeine mixture in wet-cold stress.

Our investigations were aimed at studying the possibility of enhancement of homeostatic processes protecting against excessive body cooling by using thermogenic drugs. We studied the influence of ephedrine (1 mg/kg) and caffeine (2.5 mg/kg) mixture in males immersed in cold water (12 degrees C) on core temperature and plasma catecholamines, cortisol, energy substrates and chosen cognitive functions in subjects without or after previous submission to short cold acclimation procedure by five repeated brief cold-water immersions. The tested drugs did not significantly influence core temperature during immersion both in acclimated and non-acclimated subjects, however, they enhanced metabolic response. There were observed faster mobilization and higher increase in energy substrates, more pronounced in acclimated subjects (free fatty acids, glucose). Tested drugs slightly improved some psychosomatic reactions. Although the results of our study suggest that a single application of ephedrine-caffeine mixture might probably support physiological mechanisms protecting against excessive body cooling when used in people in wet-cold conditions, further research is needed to confirm the clinical significance.

Polyunsaturated fatty acid (PUFA) changes in serum and liver of undernourished rats given dietary vitamin B6 supplementation.

The influence of vitamin B6 on linoleic (LA), alpha-linolenic (ALA), arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid content in serum and liver of rats fed with protein-energy deficient diets for 90 d, was studied. To estimate the effect of dietary supplementation with vitamin B6 on the composition and level of fatty acids in the serum and liver of rats, two experiments were performed. In these experiments control rats were fed ad libitum semisynthetic isocaloric diets of 1,466.5 kJ/100 g (350 kcal/100 g) throughout 90 d while the examined rats were offered 50% and 30% of the previously determined daily intake of the diet consumed in the control group. The experimental diet was supplemented with vitamin B6 to the level 4-times higher than in the control diet. A reduction to the half consumption of a standard diet supplemented with vitamin B6 caused a significant decrease of LA and ALA in blood serum at 30 and 60 d. At 90 d of the experiment the value of LA was lower and the content of AA was higher in comparison to the control group. After 30 d of consumption of vitamin B6 enriched diet in rats subjected to feed restriction to only 30% of the control intake, an increase of ALA and a decrease of AA, EPA and DHA were noticed in serum. At 60 d an increase of DHA was observed. Ninety days of feeding this diet caused a significant increase of AA level. Feeding animals for 90 d with a vitamin B6 enriched diet, with limited consumption to 50%, caused a significant increase of ALA content in liver. Further limitation of this diet consumption to 30%, caused a significant decrease of LA and ALA and an increase of EPA content.