Mast Cell Involvement in the Pathogenesis of Selected Musculoskeletal Diseases.

In recent years, there has been a noteworthy revival of interest in the function of mast cells (MCs) in the human body. It is now acknowledged that MCs impact a wide array of processes beyond just allergies, leading to a shift in research direction. Unfortunately, some earlier conclusions were drawn from animal models with flawed designs, particularly centered around the receptor tyrosine kinase (Kit) pathway. Consequently, several subsequent findings may have been unreliable. Thus, what is now required is a re-examination of these earlier findings. Nevertheless, the remaining data are fascinating and hold promise for a better comprehension of numerous diseases and the development of more effective therapies. As the field continues to progress, many intriguing issues warrant further investigation and analysis. For instance, exploring the bidirectional action of MCs in rheumatoid arthritis, understanding the extent of MCs' impact on symptoms associated with Ehlers-Danlos syndrome, and unraveling the exact role of the myofibroblast-mast cell-neuropeptides axis in the joint capsule during post-traumatic contractures are all captivating areas for exploration. Hence, in this review, we summarize current knowledge regarding the influence of MCs on the pathogenesis of selected musculoskeletal diseases, including rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, gout, muscle and joint injuries, tendinopathy, heterotopic ossification, and Ehlers-Danlos syndrome. We believe that this review will provide in-depth information that can guide and inspire further research in this area.

SERS performance of GaN/Ag substrates fabricated by Ag coating of GaN platforms.

The results of comparative studies on the fabrication and characterization of GaN/Ag substrates using pulsed laser deposition (PLD) and magnetron sputtering (MS) and their evaluation as potential substrates for surface-enhanced Raman spectroscopy (SERS) are reported. Ag layers of comparable thicknesses were deposited using PLD and MS on nanostructured GaN platforms. All fabricated SERS substrates were examined regarding their optical properties using UV-vis spectroscopy and regarding their morphology using scanning electron microscopy. SERS properties of the fabricated GaN/Ag substrates were evaluated by measuring SERS spectra of 4-mercaptobenzoic acid molecules adsorbed on them. For all PLD-made GaN/Ag substrates, the estimated enhancement factors were higher than for MS-made substrates with a comparable thickness of the Ag layer. In the best case, the PLD-made GaN/Ag substrate exhibited an approximately 4.4 times higher enhancement factor than the best MS-made substrate.

Investigation of organic monoradicals reactivity using surface-enhanced Raman spectroscopy.

Surface-enhanced Raman spectroscopy (SERS) and self-assembled monolayer (SAM) approaches were used to investigate the reactions of organic monoradicals with methanol. An attempt was made to generate monoradicals from thiophenols and phenylmethanethiols substituted with bromine, iodine, and nitro groups by irradiation with UV light. Monolayers of radical precursors were deposited on SERS substrates, which were then immersed in methanol and irradiated for 1 and/or 3, 6, 12 and 24 h in a UV photochemical reactor. Pre- and postreaction SERS spectra were obtained by using a confocal Raman microscope and compared with the spectra of expected products of the radical reaction with methanol. Our studies have shown that the efficiency of monoradical generation is highly dependent on the chemical structure of the precursor. In addition, it is shown that both the SERS substrate and experimental conditions used strongly influence the obtained results.

Recognized and Potentially New Biomarkers-Their Role in Diagnosis and Prognosis of Cardiovascular Disease.

Atherosclerosis and its consequences are the leading cause of mortality in the world. For this reason, we have reviewed atherosclerosis biomarkers and selected the most promising ones for review. We focused mainly on biomarkers related to inflammation and oxidative stress, such as the highly sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA2). The microRNA (miRNA) and the usefulness of the bone mineralization, glucose, and lipid metabolism marker osteocalcin (OC) were also reviewed. The last biomarker we considered was angiogenin (ANG). Our review shows that due to the multifactorial nature of atherosclerosis, no single marker is known so far, the determination of which would unambiguously assess the severity of atherosclerosis and help without any doubt in the prognosis of cardiovascular risk.

ABG Assistant-Towards an Understanding of Complex Acid-Base Disorders.

The ability to diagnose acid-base imbalances correctly is essential for physicians and other healthcare workers. Despite its importance, it is often considered too complex and confusing. Although most people dealing with arterial blood gases (ABGs) do not usually have problems with acid-base disorder assessment, such an analysis is also carried out by other healthcare workers for whom this can be a challenging task. Many aspects may be problematic, partly due to multiple data analysis methods and no definitive statement on which one is better. According to our survey, the correctness of arterial blood gas analysis is unsatisfactory, especially in mixed disorders, which do not always manifest an obvious set of symptoms. Therefore, ABG parameters can be used as an established biomarker panel, which is considered to be a powerful tool for personalized medicine. Moreover, using different approaches to analyze acid-base disorders can lead to varying diagnoses in some cases. Because of these problems, we developed a mobile application that can spot diagnostic differences by taking into account physiological and chemical approaches, including their variants, with a corrected anion gap. The proposed application is characterized by a high percentage of correct analyses and can be an essential aid for diagnosing acid-base disturbances.

Systems Approach to Study Associations between OxLDL and Abdominal Aortic Aneurysms.

Although abdominal aortic aneurysm (AAA) is a common vascular disease and is associated with high mortality, the full pathogenesis of AAA remains unknown to researchers. Abdominal aortic aneurysms and atherosclerosis are strongly related. Currently, it is more often suggested that development of AAA is not a result of atherosclerosis, however, individual factors can act independently or synergistically with atherosclerosis. One of such factors is low-density lipoprotein (LDL) and its oxidized form (oxLDL). It is known that oxLDL plays an important role in the pathogenesis of atherosclerosis, thus, we decided to examine oxLDL impact on the development of AAA by creating two models using Petri-nets. The first, full model, contains subprocess of LDL oxidation and all subprocesses in which it participates, while the second, reduced model, does not contain them. The analysis of such models can be based on t-invariants. They correspond to subprocesses which do not change the state of the modeled system. Moreover, the knockout analysis has been used to estimate how crucial a selected transition (representing elementary subprocess) is, based on the number of excluded subprocesses as a result of its knockout. The results of the analysis of our models show that oxLDL affects 55.84% of subprocesses related to AAA development, but the analysis of the nets based on knockouts and simulation has shown that the influence of oxLDL on enlargement and rupture of AAA is negligible.

Adaptation of bacteria Escherichia coli in presence of quaternary ammonium ionic liquids.

This paper presents the adaptation of Escherichia coli Gram-negative bacteria to increased concentrations of ionic liquids. Theophylline-based quaternary ammonium salts were used as an example of an ionic liquid that on the one hand includes an anion of natural origin and on the other hand is characterized by amphiphilic properties due to aliphatic chains in its structure. Theophylline-based ionic liquids can be synthesized relatively cheaply and easily and can exhibit strong antibacterial properties depending on the alkyl chain length. These compounds can also strongly affect bacterial membrane properties, including changes in electrokinetic potential as well as net surface charge. The experiments performed in this study succeeded in obtaining bacterial cultures growing at a tetradecyltrimethylammonium theophyllinate concentration three times higher than the minimum inhibition and bactericidal concentration. The adapted bacteria were characterized by intriguing changes in morphology and grew in the form of almost one-millimeter spheres in a liquid medium. It was shown that cultivation of adapted bacteria with tetradecyltrimethylammonium theophyllinate resulted in changes in the lipid membrane composition and protein patterns of the bacterial lysates, depending on the ionic liquid concentration. This study also revealed that such bacterial adaptation can increase sensitivity to antibiotics by affecting membrane properties like ionophores. These results can be potentially important with regard to synergistic or antagonistic action with other bactericidal compounds like antibiotics and nanoparticles.

5,5',6,6'-Tetranitro-2,2'-bibenzimidazole: A Thermally Stable and Insensitive Energetic Compound.

A new energetic compound, namely a secondary explosive (5,5',6,6'-tetranitro-2,2'-bibenzimidazole, TNBBI) with high thermal stability is described. TNBBI is synthesized through direct nitration of 2,2'-bibenzimidazole with nitric acid. TNBBI decomposes exothermically at 394 °C without visible melting. The heat of combustion and the standard enthalpy of formation are determined experimentally. The detonation parameters calculated for the new compound are slightly lower than those for TNT. However, the combination of TNBBI's high decomposition temperature and low sensitivity make it a promising thermally stable energetic compound. The structure of the new compound is confirmed by NMR and IR spectroscopy.

Assessing the environmental fate of S-metolachlor, its commercial product Mercantor Gold® and their photoproducts using a water-sediment test and in silico methods.

Pesticides enter surface and groundwater by several routes in which partition to sediment contributes to their fate by abiotic (e.g. photolysis, hydrolysis) and biotic processes. Yet, little is known about S-metolachlor (SM) transformation in water-sediment systems. Therefore, a newly developed screening water-sediment test (WST) was applied to compare biodegradation and sorption processes between pure SM and Mercantor Gold® (MG), a commercial formulation of SM. Photolysis in water was performed by Xe lamp irradiation. Subsequently, the biodegradability of SM and MG photolysis mixtures was examined in WST. The primary elimination of SM from water phase was monitored and structures of its TPs resulting from biotransformation (bio-TPs) were elucidated by LC-MS/MS. SM was extracted from sediment in order to estimate the role of sorption in WST for its elimination. A set of in silico prediction software tools was applied for toxicity assessment of SM and its bio-TPs. Obtained results suggest that the MG adjuvants do not significantly affect biodegradation, but do influence diffusion of SM into sediment. 50% of SM could not be re-extracted from sediment with 0.01 M CaCl2 aqueous solution recommended in OECD test guideline for adsorption. Neither the parent compound nor the photo-TPs were biodegraded. However, new bio-TPs have been generated from SM and MG photo-TPs due to bacterial activity in the water-sediment interphase. Moreover, according to in silico assessment of the bio-TPs the biotransformation might lead to an increased toxicity to the water organisms compared with the SM. This might raise concerns of bio-TPs presence in the environment.

Photolytic transformation products and biological stability of the hydrological tracer Uranine.

Among many fluorescence tracers, Uranine (sodium fluorescein, UR) has most widely been used in hydrological research. Extensive use of UR for tracing experiments or commercial use might cause a potential risk of long-term environmental contamination. As any organic substance released to the environment, also UR is subjected to chemical and physical reactions that can be chemical, biological and photolysis processes. These processes transform the parent compound (PC) and have not been extensively investigated for UR. This study applies two OECDs (301 D and 301 F) tests and a screening water sediment test (WST) to investigate the biodegradability of the PC. Photolysis in water was explored by Xe lamp irradiation. Subsequently, the biodegradability of the photolysis mixtures was examined. The primary elimination of UR was monitored and structures of its transformation products (TPs) were elucidated by HPLC-FLD-MS/MS. UR was found not readily biodegradable, although small degradation rates could be observed in the OECD 301 D and WST. HPLC-FLD analysis showed high primary elimination of the tracer during photolysis. However, the low degree of mineralization found indicates that the UR was not fully degraded, instead transformed to TPs. A total of 5 photo-TPs were identified. According to MS/MS data, chemical structures could be proposed for all identified photo-TPs. Likewise the parent compound it was demonstrated that photo-TPs were largely recalcitrant to microbial degradation. Although we did not find indications for toxicity, target-oriented studies on the environmental impact of these photo-TPs are warranted. Results obtained in this study show that deeper investigations are necessary to fully understand fate and risk connected to the use of UR.

A comparative assessment of the transformation products of S-metolachlor and its commercial product Mercantor Gold(®) and their fate in the aquatic environment by employing a combination of experimental and in silico methods.

Even appropriately used, pesticides can enter the surface and groundwater by several routes where photochemical degradation along with biotic processes contributes to their fate, resulting sometimes in the formation of stable transformation products (TPs). Yet, little is known about S-metolachlor (SM) transformation in the aquatic environment. Furthermore, commercial formulation of a pesticide might have different physical and biological properties compared to its pure grade. The present study assessed the biodegradability of the pure SM and its commercial product Mercantor Gold(®) (MG) by employing two OECD biodegradation (301D, F) tests. Photolysis in water was investigated by using a Xe lamp. Subsequently the biodegradability of the photolysis mixtures was examined. The primary elimination of SM was monitored and structures of its TPs were elucidated by HPLC-UV-MS/MS. Additionally, a set of in silico prediction programs was applied for supporting analytical results and toxicity assessment of SM and TPs. S-metolachlor and Mercantor Gold(®) were not biodegraded. HPLC-UV analysis showed higher elimination of SM in MG compared to pure SM during photolysis. A total of 10 photo-TPs of SM and MG were identified. According to MS data and in silico predictions, chemical structures were proposed for all found photo-TPs. Likewise for the parent compounds, no biodegradation has been observed for their photo-TPs. However, in the 301F test new bio-TPs have been generated from photo-TPs which were observed for the first time according to authors' best knowledge. The results suggest that the MG formulation does not affect the biodegradation process, but it influences the photolysis efficiency and potentially might result in faster formation of TPs in the environment. This study also demonstrates that photo-TPs can be further transformed into new products due to bacterial activity in the water phase. Moreover biotransformation might lead to an increased toxicity compared with the parent compound.