Osseointegration of hydroxyapatite coatings doped with silver nanoparticles: scanning electron microscopy studies on a rabbit model

Background: Modern joint arthroplasties rely on osseointegration of metal components through bone ingrowth into hydroxyapatite (HA) layers. However, such surfaces are prone to colonisation by bacteria and formation of biofilms. Application of silver nanoparticles (SNs) to hydroxyapatite coatings could reduce the risk of infection; however, little is known about how this would affect the process of bone ingrowth. This study examined osseointegration of conventional and SN doped HA coatings in a rabbit model.  Materials and methods: In this study, 12 cylindrical implants coated with conven- tional and SN doped HA were implanted into New Zealand white rabbit femora, with each animal receiving both types of implants. After 12 weeks, rabbits were sacrificed, their femora were harvested and implants removed during pull-out testing. Retrieved samples were dehydrated, sputter coated and observed using a scanning electron microscope (SEM) to verify bony ingrowth and retention of SNs.  Results: The percentage of implant in direct contact with bone was measured in cross-sections of implants. The SEM analysis demonstrated that osseointegration of the SN doped coatings was similar to the conventional HA samples. A similar morphology of newly formed trabecular bone was observed in both implants, with silver doped HA-coated implants retaining multiple nanoparticles in areas which were not overgrown by bone. Analysis of the bone-implant contact area revealed comparable results for both types of coatings. These finding indicated that SN doped HA coatings are characterised by good osseointegrative properties.  Conclusions: Since SNs were found in areas not covered by mineralised bone, it is assumed that the antimicrobial properties of the modified coating may be retained for 12 weeks after implantation. Additional studies are required to fine--tune the composition of HA coatings with SNs, to ensure optimal osseointegrative and antimicrobial properties.

Metabolomic and transcriptomic response to imatinib treatment of gastrointestinal stromal tumour in xenograft-bearing mice

Background Although imatinib is a well-established first-line drug for treating a vast majority of gastrointestinal stromal tumours (GIST), GISTs acquire secondary resistance during therapy. Multi-omics approaches provide an integrated perspective to empower the development of personalised therapies through a better understanding of functional biology underlying the disease and molecular-driven selection of the best-targeted individualised therapy. In this study, we applied integrative metabolomic and transcriptomic analyses to elucidate tumour biochemical processes affected by imatinib treatment. Materials and methods A GIST xenograft mouse model was used in the study, including 10 mice treated with imatinib and 10 non-treated controls. Metabolites in tumour extracts were analysed using gas chromatography coupled with mass spectrometry (GC-MS). RNA sequencing was also performed on the samples subset (n=6). Results Metabolomic analysis revealed 21 differentiating metabolites, whereas next-generation RNA sequencing data analysis resulted in 531 differentially expressed genes. Imatinib significantly changed the profile of metabolites associated mainly with purine and pyrimidine metabolism, butanoate metabolism, as well as alanine, aspartate, and glutamate metabolism. The related changes in transcriptomic profiles included genes involved in kinase activity and immune responses, as well as supported its impact on the purine biosynthesis pathway. Conclusions Our multi-omics study confirmed previously known pathways involved in imatinib anticancer activity as well as correlated imatinib-relevant downregulation of expression of purine biosynthesis pathway genes with the reduction of respectful metabolites. Furthermore, considering the importance of the purine biosynthesis pathway for cancer proliferation, we identified a potentially novel mechanism for the anti-tumour activity of imatinib. Based on the results, we hypothesise metabolic modulations aiming at the reduction in purine and pyrimidine pool may ensure higher imatinib efficacy or re-sensitise imatinib-resistant tumours.publishedVersio

New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans

Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease.This research was supported by the Polish National Science Center (2014/13/N/NZ7/04231), the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2014-58920R), by the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional (FEDER) (PI14-01427), and by the quality-promoting subsidy from the Ministry of Science and Higher Education of Poland, Leading National Research Centre (KNOW programme 2012-2017). The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

2014 iAREA campaign on aerosol in Spitsbergen – Part 2: Optical properties from Raman-lidar and in-situ observations at Ny-Ålesund

In this work multi wavelength Raman lidar data from Ny-Ålesund, Spitsbergen have been analysed for the spring 2014 Arctic haze season, as part of the iAREA campaign. Typical values and probability distributions for aerosol backscatter, extinction and depolarisation, the lidar ratio and the color ratio for 4 different altitude intervals within the troposphere are given. These quantities and their dependencies are analysed and the frequency of altitude-dependent observed aerosol events are given. A comparison with ground-based size distribution and chemical composition is performed. Hence the aim of this paper is to provide typical and statistically meaningful properties of Arctic aerosol, which may be used in climate models or to constrain the radiative forcing. We have found that the 2014 season was only moderately polluted with Arctic haze and that sea salt and sulphate were the most dominant aerosol species. Moreover the drying of an aerosol layer after cloud disintegration has been observed. Hardly any clear temporal evolution over the 4 week data set on Arctic haze is obvious with the exception of the extinction coefficient and the lidar ratio, which significantly decreased below 2 km altitude by end April. In altitudes between 2 and 5 km the haze season lasted longer and the aerosol properties were generally more homogeneous than closer to the surface. Above 5 km only few particles were found. The variability of the lidar ratio is discussed. It was found that knowledge of the aerosol’s size and shape does not determine the lidar ratio. Contrary to shape and lidar ratio, there is a clear correlation between size and backscatter: larger particles show a higher backscatter coefficient

Treatment of overweight and obesity during and after a pandemic. Let’s not wait for the development of complications — new guidelines for doctors

Guidelines developed by Experts endorsed by the Polish Association for the Study of Obesity, Polish Psychiatric Association, Polish Society of Hypertension, Scientific Section of Telepsychiatry of the Polish Psychiatric Association, Polish Association of Cardiodiabetology, Polish Association of Endocrinology, and The College of Family Physicians in Poland Social patronage of the Foundation for People with Obesity OD-WAGA    The treatment of obesity in the pandemic era has become more important than ever. The current situation is conducive to the worsening of disease and the development of new diseases, mainly as a result of compensating negative emotions with food. Taking into account the data on the impact of obesity and its complications on the severity of the course and the risk of death due to COVID-19, we recommend using the 2016 American Endocrine Society’s criteria for the diagnosis of obesity instead of the 1998 WHO criteria. We also recommend diagnosing eating under the influence of emotions and the occurrence of eating disturbances, such as compulsive eating syndrome, night eating syndrome and food addiction, and complications of obesity, in any person with a BMI ≥ 25 kg/m2. The approach to treatment should be individualised and should not be limited to nutritional and physical activity education alone. Each patient should be offered appropriately selected pharmacotherapy, and, if necessary, also psychotherapy. The first-line drug should be a combined preparation containing naltrexone and bupropion (Mysimba®). Liraglutide in a dose of 3 mg (Saxenda®) should be considered as a second-line drug in a situation where eating under the influence of emotions is excluded (reaching for food in situations of experiencing negative and positive emotions and boredom, eating disturbances: compulsive eating syndrome, night eating syndrome, and food addiction) and depressed mood or there are permanent contraindications to the use of the first-line drug. It is unethical not to treat obesity or refer the patient to another doctor for treatment. The use of telemedicine tools can facilitate work in therapeutic teams (doctor, dietitian, psychotherapist), as well as improve patient compliance with pharmacotherapy and changes in eating habits and the level of physical activity recommendations

Leczenie nadwagi i otyłości w czasie i po pandemii. Nie czekajmy na rozwój powikłań — nowe wytyczne dla lekarzy

Wytyczne opracowane przez Ekspertów pod patronatem Polskiego Towarzystwa Badań nad Otyłością, Polskiego Towarzystwa Psychiatrycznego, Polskiego Towarzystwa Nadciśnienia Tętniczego, Sekcji Naukowej Telepsychiatrii Polskiego Towarzystwa Psychiatrycznego, Polskiego Towarzystwa Kardiodiabetologicznego, Polskiego Towarzystwa Endokrynologicznego i Kolegium Lekarzy Rodzinnych w Polsce Patronat społeczny Fundacji Osób Chorych na Otyłość OD-WAGA Leczenie otyłości w dobie pandemii stało się jeszcze ważniejsze niż do tej pory. Aktualna sytuacja sprzyja rozwojowi istniejącej choroby, jak również nowym zachorowaniom, przede wszystkim z powodu kompensowania negatywnych emocji jedzeniem. Biorąc pod uwagę dane dotyczące wpływu otyłości i jej powikłań na przebieg i ryzyko zgonu z powodu COVID-19, rekomendujemy diagnozowanie otyłości z zastosowaniem kryteriów Amerykańskich Towarzystw Endokrynologicznych z 2016 r. zamiast kryteriów WHO z roku 1998. Zalecamy również diagnozowanie jedzenia pod wpływem emocji oraz takich zaburzeń odżywiania, jak zespół kompulsywnego jedzenia, zespół nocnego jedzenia i nałogowe jedzenie, oraz powikłań otyłości u każdej osoby z BMI > 25 kg/m2. Podejście do leczenia powinno być zindywidualizowane i nie powinno ograniczać się do edukacji żywieniowej oraz wskazań dotyczących aktywności fizycznej. Każdemu choremu należy proponować odpowiednio dobraną farmakoterapię, a w razie potrzeby również psychoterapię. Lekiem I rzutu powinien być preparat złożony, który zawiera naltrekson i bupropion (Mysimba®). Liraglutyd w dawce 3 mg (Saxenda®) powinien być brany pod uwagę jako lek II rzutu, gdy zostaną wykluczone jedzenie pod wpływem emocji (sięganie po jedzenie w sytuacjach przeżywania emocji negatywnych i pozytywnych, nudy, zaburzenia odżywiania: zespół kompulsywnego jedzenia, zespół nocnego jedzenia i nałogowe jedzenie), obniżony nastrój lub istnieją trwałe przeciwwskazania do zastosowania leku I rzutu. Niepodejmowanie leczenia otyłości lub  nieskierowanie chorego do innego lekarza, który podejmie się jej leczenia, jest postępowaniem nieetycznym. Wykorzystanie narzędzi telemedycyny może ułatwić pracę w zespołach terapeutycznych (lekarz, dietetyk, psychoterapeuta), a także poprawić stosowanie się pacjentów do zaleceń dotyczących farmakoterapii, zmian nawyków żywieniowych i podjęcia aktywności fizycznej

New biochemical insights into the mechanisms of pulmonary arterial hypertension in humans

Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease

Chasing Graphene-Based Anticancer Drugs: Where are We Now on the Biomedical Graphene Roadmap?

Katarzyna Uzdrowska,1 Narcyz Knap,1 Jacek Gulczynski,2 Alicja Kuban-Jankowska,1 Wiktoria Struck-Lewicka,3 Michal J Markuszewski,3 Tomasz Bączek,3 Ewa Izycka-Swieszewska,2 Magdalena Gorska-Ponikowska1 1Department of Medical Chemistry, Medical University of Gdansk, Gdansk, 80-211, Poland; 2Faculty of Health Sciences with the Institute of Maritime and Tropical Medicine, Medical University of Gdansk, Gdansk, 80-211, Poland; 3Faculty of Pharmacy, Medical University of Gdansk, Gdansk, 80-416, PolandCorrespondence: Magdalena Gorska-Ponikowska, Department of Medical Chemistry, Medical University of Gdansk, 1 Debinki St, Gdansk, 80-211, Poland, Tel +48 58 349 14 50, Fax +48 58 349 14 56, Email [email protected]: Graphene and graphene-based materials have attracted growing interest for potential applications in medicine because of their good biocompatibility, cargo capability and possible surface functionalizations. In parallel, prototypic graphene-based devices have been developed to diagnose, imaging and track tumor growth in cancer patients. There is a growing number of reports on the use of graphene and its functionalized derivatives in the design of innovative drugs delivery systems, photothermal and photodynamic cancer therapy, and as a platform to combine multiple therapies. The aim of this review is to introduce the latest scientific achievements in the field of innovative composite graphene materials as potentially applied in cancer therapy. The “Technology and Innovation Roadmap” published in the Graphene Flagship indicates, that the first anti-cancer drugs using graphene and graphene-derived materials will have appeared on the market by 2030. However, it is necessary to broaden understanding of graphene-based material interactions with cellular metabolism and signaling at the functional level, as well as toxicity. The main aspects of further research should elucidate how treatment methods (e.g., photothermal therapy, photodynamic therapy, combination therapy) and the physicochemical properties of graphene materials influence their ability to modulate autophagy and kill cancer cells. Interestingly, recent scientific reports also prove that graphene nanocomposites modulate cancer cell death by inducing precise autophagy dysfunctions caused by lysosome damage. It turns out as well that developing photothermal oncological treatments, it should be taken into account that near-infrared-II radiation (1000– 1500 nm) is a better option than NIR-I (750– 1000 nm) because it can penetrate deeper into tissues due to less scattering at longer wavelengths radiation.Keywords: graphene-based materials, oncological therapies, cancer treatment, biomedical innovations, drugs delivery system

The state-of-the-art determination of urinary nucleosides using chromatographic techniques “hyphenated” with advanced bioinformatic methods

Over the last decade metabolomics has gained increasing popularity and significance in life sciences. Together with genomics, transcriptomics and proteomics, metabolomics provides additional information on specific reactions occurring in humans, allowing us to understand some of the metabolic pathways in pathological processes. Abnormal levels of such metabolites as nucleosides in the urine of cancer patients (abnormal in relation to the levels observed in healthy volunteers) seem to be an original potential diagnostic marker of carcinogenesis. However, the expectations regarding the diagnostic value of nucleosides may only be justified once an appropriate analytical procedure has been applied for their determination. The achievement of good specificity, sensitivity and reproducibility of the analysis depends on the right choice of the phases (e.g. sample pretreatment procedure), the analytical technique and the bioinformatic approach. Improving the techniques and methods applied implies greater interest in exploration of reliable diagnostic markers. This review covers the last 11 years of determination of urinary nucleosides conducted with the use of high-performance liquid chromatography in conjunction with various types of detection, sample pretreatment methods as well as bioinformatic data processing procedures