Identification of a new genetic variant (G231N, E232T, N235D) of peptidylarginine deiminase from P. gingivalis in advanced periodontitis.

Chronic periodontitis (CP), an inflammatory disease of periodontal tissues driven by a dysbiotic subgingival bacterial biofilm, is also associated with several systemic diseases, including rheumatoid arthritis (RA). Porphyromonas gingivalis, one of the bacterial species implicated in CP as a keystone pathogen produces peptidyl arginine deiminase (PPAD) that citrullinates C-terminal arginine residues in proteins and peptides. Autoimmunity to citrullinated epitopes is crucial in RA, hence PPAD activity is considered a possible mechanistic link between CP and RA. Here we determined the PPAD enzymatic activity produced by clinical isolates of P. gingivalis, sequenced the ppad gene, and correlated the results with clinical determinants of CP in patients from whom the bacteria were isolated. The analysis revealed variations in PPAD activity and genetic diversity of the ppad gene in clinical P. gingivalis isolates. Interestingly, the severity of CP was correlated with a higher level of PPAD activity that was associated with the presence of a triple mutation (G231N, E232T, N235D) in PPAD in comparison to W83 and ATCC 33277 type strains. The relation between mutations and enhanced activity was verified by directed mutagenesis which showed that all three amino acid residue substitutions must be introduced into PPAD expressed by the type strains to obtain the super-active enzyme. Cumulatively, these results may lead to the development of novel prognostic tools to assess the progress of CP in the context of associated RA by analyzing the ppad genotype in CP patients infected with P. gingivalis.

Medical Applications of Silver and Gold Nanoparticles and Core-Shell Nanostructures Based on Silver or Gold Core: Recent Progress and Innovations.

Nanoparticles (NPs) of noble metals such as silver (Ag NPs) or gold (Au NPs) draw the attention of scientists looking for new compounds to use in medical applications. Scientists have used metal NPs because of their easy preparation, biocompatibility, ability to influence the shape and size or modification, and surface functionalization. However, to fully use their capabilities, both the benefits and their potential threats should be considered. One possibility to reduce the potential threat and thus prevent the extinction of their properties resulting from the agglomeration, they are covered with a neutral material, thus obtaining core-shell nanostructures that can be further modified and functionalized depending on the subsequent application. In this review, we focus on discussing the properties and applications of Ag NPs and Au NPs in the medical field such as the treatment of various diseases, drug carriers, diagnostics, and many others. In addition, the following review also discusses the use and potential applications of Ag@SiO2 and Au@SiO2 core-shell nanostructures, which can be used in cancer therapy and diagnosis, treatment of infections, or tissue engineering.

SAM, SAH and C. elegans longevity: insights from a partial AHCY deficiency model.

Supplementation with S-adenosylhomocysteine (SAH) extends the lifespan of model organisms. To explore the impact of SAH on aging, we generated a Caenorhabditis elegans model by introducing the S-adenosylhomocysteine hydrolase (AHCY-1) variant Y145C, corresponding to the human AHCY Y143C pathogenic mutation. This mutation is anticipated to impair SAH hydrolysis, resulting in its increased levels. Our findings revealed that animals with this endogenous mutation exhibited delayed aging, accompanied by decreased S-adenosylmethionine (SAM) and moderately increased SAH levels. The extended lifespan of these worms depends on the AMP-activated protein kinase (AMPK), its activator Vaccinia virus-related kinase (VRK-1), and the DAF-16 transcription factor. The results underline the complex nature of SAH's influence on aging, proposing that the balance between SAM and SAH might play a pivotal role in defining the lifespan of C. elegans. Moreover, our partial AHCY-1 deficiency model offers a tool for studying the intersection of methionine metabolism and aging.

Analysis of miRNAs in Osteogenesis imperfecta Caused by Mutations in COL1A1 and COL1A2: Insights into Molecular Mechanisms and Potential Therapeutic Targets.

Osteogenesis imperfecta (OI) is a group of connective tissue disorders leading to abnormal bone formation, mainly due to mutations in genes encoding collagen type I (Col I). Osteogenesis is regulated by a number of molecules, including microRNAs (miRNAs), indicating their potential as targets for OI therapy. The goal of this study was to identify and analyze the expression profiles of miRNAs involved in bone extracellular matrix (ECM) regulation in patients diagnosed with OI type I caused by mutations in COL1A1 or COL1A2. Primary skin fibroblast cultures were used for DNA purification and sequence analysis, followed by analysis of miRNA expression. Sequencing analysis revealed mutations of the COL1A1 or COL1A2 genes in all OI patients, including four previously unreported. Amongst the 40 miRNAs analyzed, 9 were identified exclusively in OI cells and 26 in both OI patients and the controls. In the latter case, the expression of six miRNAs (hsa-miR-10b-5p, hsa-miR-19a-3p, hsa-miR-19b-3p, has-miR-204-5p, has-miR-216a-5p, and hsa-miR-449a) increased, while four (hsa-miR-129-5p, hsa-miR-199b-5p, hsa-miR-664a-5p, and hsa-miR-30a-5p) decreased significantly in OI cells in comparison to their expression in the control cells. The identified mutations and miRNA expression profiles shed light on the intricate processes governing bone formation and ECM regulation, paving the way for further research and potential therapeutic advancements in OI and other genetic diseases related to bone abnormality management.

Crystal Lattice Defects in Deuterated Zr in Presence of O and C Impurities Studied by PAS and XRD for Electron Screening Effect.

Low-energy nuclear reactions are known to be extremely dependent on the local crystal structure and crystal defects of the deuterated samples. This has a strong influence on both hydrogen diffusion and the effective electron mass. The latter determines the strength of the local electron-screening effect and can change the deuteron-deuteron reaction rates at very low energies by many orders of magnitude. In the present study, zirconium samples were exposed to various conditions and energies of deuteron beams using the unique accelerator system with ultra-high vacuum, installed in the eLBRUS laboratory at the University of Szczecin. Irradiated and virgin samples were investigated by means of the X-ray diffraction (XRD) and positron annihilation spectroscopy (PAS). While the first method delivers information about changes of crystal lattice parameters and possible production of hydrides accompanying the formation of dislocations that are produced during irradiation of the samples, the second one can determine the depth distribution of crystal defects, being especially sensitive to vacancies. The studied Zr samples were also implanted by carbon and oxygen ions in order to simulate the real situation taking place in nuclear reaction experiments and to investigate their influence on the kinetic of produced vacancies. The observed enhancement of the electron-screening effect in the deuteron fusion reaction at very low energies could be explained by formation of a high number of vacancies during the deuteron irradiation of samples. Possible carbon and oxygen impurities can affect this process in various ways by changing the depth distribution of vacancies and their diffusion, but they play only a minor role in the strength of the electron-screening effect.

Plutonium isotopes in the ground air layer in southern Poland (2010-2016): Source terms, seasonal variability and correlations with meteorological conditions.

In this study, the results of the analysis of Pu-238 and Pu-239 + 240 activity concentrations on aerosol filters collected from 2010 to 2016 in Krakow (Southern Poland) are presented and discussed. For the first time, the temporal variation of Pu-239 + 240 activity concentration in surface air in Poland was studied using Fourier analysis. The analysis clearly showed that the Pu-239 + 240 content in the near-ground air layer is subject to seasonal variations and demonstrates annual periodicity. Pu analyses were performed using alpha spectrometry. The measured values ranged from 1.93∙10-10 Bq/m3 to 1.31∙10-8 Bq/m3 with an average of 2.07∙10-9 Bq/m3 for Pu-239 + 240 and from 9.07∙10-11 Bq/m3 to 1.27∙10-9 Bq/m3 with the average 1.52∙10-10 Bq/m3 for Pu-238. The analysis of the potential sources of plutonium isotopes in the air aerosols samples indicated that only two samples are uniquely characterized by the ratio corresponding to spent nuclear fuel: February 2012 (0.59 ± 0.18) and February 2015 (0.68 ± 0.19). The remaining samples showed mixed origins, with global radioactive fallout appearing to contribute more than spent nuclear fuel. To study the relationship between Pu-239 + 240 and meteorological conditions, Pearson's correlation and circulation pattern analyses were performed. The analyses showed that the Pu-239 + 240 activity concentration depends on air temperature (R = 0.51), the sum of ice and snowfall (R = -0.45), relative humidity (R = -0.54) and mean total cloud cover (R = -0.56). High concentrations of Pu-239 + 240 were positively correlated with air advection from the southern and eastern sectors, whereas low concentrations were observed during dynamic weather conditions with intense circulation from the western sector. In case of Pu-238 no significant correlation was observed.

Factor VII Activating Protease (FSAP) and Its Importance in Hemostasis-Part I: FSAP Structure, Synthesis and Activity Regulation: A Narrative Review.

Factor VII activating protease (FSAP) was first isolated from human plasma less than 30 years ago. Since then, many research groups have described the biological properties of this protease and its role in hemostasis and other processes in humans and other animals. With the progress of knowledge about the structure of FSAP, several of its relationships with other proteins or chemical compounds that may modulate its activity have been explained. These mutual axes are described in the present narrative review. The first part of our series of manuscripts on FSAP describes the structure of this protein and the processes leading to the enhancement and inhibition of its activities. The following parts, II and III, concern the role of FSAP in hemostasis and in the pathophysiology of human diseases, with particular emphasis on cardiovascular diseases.

Chromosomal radiosensitivity of human breast carcinoma cells and blood lymphocytes following photon and proton exposures.

Breast carcinomas (BC) are among the most frequent cancers in women. Studies on radiosensitivity and ionizing radiation response of BC cells are scarce and mainly focused on intrinsic molecular mechanisms but do not include clinically relevant features as chromosomal rearrangements important for radiotherapy. The main purpose of this study was to compare the ionizing radiation response and efficiency of repair mechanisms of human breast carcinoma cells (Cal 51) and peripheral blood lymphocytes (PBL) for different doses and radiation qualities (60Co γ-rays, 150 MeV and spread-out Bragg peak (SOBP) proton beams). The radiation response functions obtained using the conventional metaphase assay and premature chromosome condensation (PCC) technique enabled us to determine the number of chromosomal breaks at different time after irradiation. Both cytogenetic assays used confirmed the higher biological radiosensitivity for proton beams in tumor cells compared to PBL, corresponding to higher values of the linear LQ parameter α. additionally, the ratio of the LQ parameters ß/α describing efficiency of the repair mechanisms, obtained for chromosome aberrations, showed higher numbers for PBL than for Cal 51 for all exposures. Similar results were observed for the ratio of PCC breaks determined directly after irradiation to that obtained 12 h later. This parameter (t0/t12) showed faster decrease of the repair efficiency with increasing LET value for Cal 51 cells. This finding supports the use of the proton therapy for breast cancer patients.

222Rn and 226Ra concentrations in selected shallow circulation groundwaters from the Fore-Sudetic Monocline area.

Natural radioactive isotopes occur in various components of the natural environment, including groundwater. The general population, not always aware of possible threats, can use its resources. The activity concentration of some of the radioactive isotopes should be monitored, especially in those intakes from which it is possible to obtain water for human consumption, e.g. in domestic wells. The conducted research was innovative due to the fact that in many countries, including Poland, there are no regulations on waters exploited from home wells using as a drinking water source. As the groundwaters from this area have not been examined for radon (222Rn) and radium (226Ra) occurrence yet, the goal of this research was to perform screening tests in this part of the Fore-Sudetic Monocline. For this purpose, the authors have measured the concentration of 222Rn and 226Ra activity in groundwater collected from this geological unit located in south-western Poland. 222Rn and 226Ra occurrence was researched, and specific electrolytic conductivity, redox potential, pH and temperature were measured in 52 groundwater samples. 222Rn activity concentration ranged from 0.18 to 19.78 Bq/dm3. Only in three cases, 226Ra activity concentration reached a value above the lower detection limit of the applied method, i.e. 0.05 Bq/dm3 (max. 0.77 Bq/dm3). The authors present completely new data on the occurrence of these radioactive isotopes in the waters of the first aquifer in the Fore-Sudetic Monocline, which is not without significance for the health of consumers of these waters.

Novelty Cosmetic Filters Based on Nanomaterials Composed of Titanium Dioxide Nanoparticles.

The following work describes the synthesis of new physical filters based on TiO2/SiO2 and TiO2/Ag nanostructures. Titanium dioxide nanoparticles (TiO2 NPs) were applied as control material and a popular physical UV filter. The advantage of using materials on the nanometer scale is the elimination of the skin whitening effect that occurs when using photoprotective cosmetics containing titanium dioxide on a macro scale. In addition, the silica coating makes the material less harmful, and the silver coating enriches the material with antibacterial properties. Nanoparticles and nanostructures have been characterized by Energy Dispersive X-Ray Analysis (EDX), the Scanning Electron Microscope (SEM), Transmission Electron Microscopy (TEM), and Fourier-Transform Infrared Spectroscopy (FT-IR) methods. Due to the use of physical filters in anti-radiation protection cosmetics, water-in-oil (W/O) emulsion has been prepared. All cosmetic formulations have been tested for stability. The sun protection research with the Sun Protection Diagnostic SP37 was carried out. These studies made it possible to determine the natural sun protection time and to compare the synthesized materials. Furthermore, one of the most important parameters when describing this type of cosmetic is water resistance, which has also been measured. The results show that the new type of material of TiO2/Ag used as a new physical filter in emulsion W/O shows the best sun protection compared with other obtained nanomaterials. It is most likely due to the improved optical properties of the combination of noble metals, for example, silver with TiO2.

The Hemisphere of the Brain in Which a Stroke Has Occurred Visible in the Heart Rate Variability.

The aim of this study was to assess whether heart rate variability (HRV) could predict which hemisphere of the brain was affected during an acute ischemic stroke (AIS). To achieve this goal, we compared HRV between patients with a right (RH) and left hemispheric (LH) stroke. The studied group consisted of 64 patients with AIS (25 with RH and 39 with LH stroke, with a mean age of 64 ± 12 and 66 ± 13, p = 0.3, respectively) using 24 h Holter ECG records at NN intervals performed at a mean of 4.3 ± 2 days following their AIS. Standard linear methods were used to analyze HRV in the time and frequency domains, as well as nonlinear methods, including sample entropy, detrended fluctuation analysis, and asymmetry measures. Patients with an LH stroke had significantly greater values for sample entropy compared to subjects with an RH stroke (1.31 ± 0.53 vs. 0.92 ± 0.46, p = 0.003, Bonferroni-corrected p = 0.033, effect size = 0.8). The LH stroke group also had higher RMSSD (113 ± 81 vs. 76 ± 61, p = 0.06), pNN50 (33.35 ± 28.54 vs. 18.52 ± 23.75, p = 0.02), and HFnu (48.42 ± 16.41 vs. 42.66 ± 17.88, p = 0.11) values, when compared to the RH group, which was possibly related to higher activity in the parasympathetic system in the LH group. Conversely, subjects with RH stroke had higher LFnu (57.34 ± 17.88 vs. 51.58 ± 16.41, p-value = 0.11) and LF/HF ratios (2.24 ± 2.87 vs. 1.68 ± 2.50, p-value = 0.11), which were likely related to higher activity in the sympathetic nervous system, when compared to the LH stroke group. Our pilot study demonstrated that patients with RH stroke had lower HRV complexity than those with LH stroke, indicating that HRV could be useful in the discrimination of hemispheric involvement in AIS.

Anti-IgLON5 Disease - The Current State of Knowledge and Further Perspectives.

Anti-IgLON5 disease is a relatively new neurological entity with the first cases reported in 2014. So far, less than 70 articles on this topic have been published. Due to its unspecific symptomatology, diverse progression, novelty and ambiguous character, it remains a difficulty for both clinical practitioners and scientists. The aim of this review is to summarize the current knowledge concerning anti-IgLON5 disease; mechanisms underlying its cause, symptomatology, clinical progression, differential diagnosis and treatment, which could be helpful in clinical practice and future research.

Case Report: Trichosporon japonicum Fungemia in a Pediatric Patient With Refractory Acute B Cell Lymphoblastic Leukemia.

Trichosporon japonicum is a very rare opportunistic yeast causing fungal disease in humans, especially in immunocompromised hosts. Here, we describe a new case of T. japonicum isolated from the blood of a pyrexial pediatric patient with refractory acute B cell lymphoblastic leukemia and acute respiratory distress. Prompt diagnosis through early clinical suspicion and appropriate molecular microbiology analysis allowed the yeast to be accurately identified at species level. Subsequent drug susceptibility testing and focused antifungal treatment with voriconazole and amphotericin B led to a complete clinical and mycological resolution of the infection, which represents the second successful case of T. japonicum bloodstream infection described in literature to date.

Comparison of responses to artificial spawning of ruffe (Gymnocephalus cernua) specimens captured from their natural habitat to those produced in cultured conditions.

Although ruffe (Gymnocephalus cernua) are widely distributed in Eurasia, in some regions (i.e., North America) ruffe are considered an invasive species. There have been no reports on artificial reproduction of this species. A study, therefore, was conducted to evaluate reproduction of ruffe with results of specimens captured from their natural habitat and cultured (F1 generation) specimens being compared. Spawning specimens from both stocks were treated with hormonal preparations: carp pituitary homogenate (CPH), Ovopel, Ovaprim and human chorionic gonadotropin (hCG) and results were analyzed by comparing response to the specimens of control groups. Spermiation outcomes and sperm motility of the captured and cultured ruffe were similar and with all hormonal treatments, there was a slightly greater sperm motility (55.6 %-57.1 %) in comparison to specimens of control groups (46.7 %-47.1 %). For captured specimens, there was no asynchronous development of oocytes, whereas in cultured specimens 32 % of females had asynchronous development of oocytes. The ovulation rate in specimens of all treated groups was 100 %, whereas specimens in the control groups did not reproductively mature and have ovulations. The latency time from time of hormonal treatments to initiation of reproductive functions depended on the spawning agent used and oocyte maturation stage and there was the shortest latency after using CPH and the longest with hCG treatment. The embryo survival and hatching rates varied with use of different hormonal preparations to induce reproduction: greatest hatching rates with hCG treatment (86.4 %-88.9 %), followed by Ovaprim (78.2 %-80.2 %) and least hatching rate with Ovopel and CPH treatments (66.0 %-67.1 % and 64.0 %-66.0 %, respectively).

Dietary ARA Improves COX Activity in Broodstock and Offspring Survival Fitness of a Model Organism (Medaka Oryzias latipes).

A 3-week feeding trial was conducted in medaka broodstock (age five months) to examine the effect of dietary arachidonic acid (ARA) level (range: 4-23 mg g-1 of total fatty acids (TFAs)) on fertility, cyclooxygenase (COX) activity, egg size, sperm motility parameters, hatching rate and weight of hatch, survival and growth of larvae. After spawn induction and dietary exposure to 4 mg ARA g-1 TFA, broodstock were fed a diet containing ARA in the amounts: 4 (continued, as control), 5, 14 and 23 mg g-1 TFA. COX1 activity in the liver and the number of COX2-positive cells in the ovaries was increased in females fed the diets containing the two highest amounts of ARA. The highest sperm motility parameters were observed in males fed a diet containing 23 mg ARA g-1 TFA. The hatchability rate and bodyweight of hatchlings were higher in the group obtained from broodstock fed a diet containing 23 mg ARA g-1 TFA (79% and 0.66 mg fish-1, respectively) compared with 4 mg ARA g-1 TFA (50% and 0.40 mg fish-1). The average mortality of offspring obtained from this group at 7 days post hatching was significantly higher than that of all other groups.

Modeling of chromosome aberration response functions induced by particle beams with different LET.

This study is based on our already published experimental data (Kowalska et al. in Radiat Environ Biophys 58:99-108, 2019) and is devoted to modeling of chromosome aberrations in human lymphocytes induced by 22.1 MeV/u 11B ions, 199 MeV/u 12C ions, 150 MeV and spread-out Bragg peak (SOBP) proton beams as well as by 60Co γ rays. The curvature of the dose-effect curves determined by the linear-quadratic model was considered in the frame of a simple analytical approach taking into account increase in the irradiation dose due to overlapping interaction regions of ion tracks. The model enabled to estimate effective interaction radius which could be compared with the physical expectations. The results were also compared to the Amorphous Track Structure Model of Katz which allows to get some additional information about the ion track structure. The analysis showed that the curvature of the experimental dose-effect curves mainly results from highly efficient repair processes of the DNA damage.

Production and distribution of chromosome aberrations in human lymphocytes by particle beams with different LET.

We investigated induction of chromosome aberrations (CA) in human lymphocytes when exposed to 150 MeV and spread out Bragg peak (SOBP) proton beams, and 199 MeV/u carbon beam which are currently widely used for cancer treatment and simultaneously are important components of cosmic radiation. For a comparison, the boron ions of much lower energy 22 MeV/u and a 60Co γ rays were used. Dose-effect curves as well as the distributions of CA were studied using Poisson and Neyman type A statistics. Systematics of experimentally determined parameters, their dependence on applied doses and irradiation quality are presented.

Dietary resveratrol improves immunity but reduces reproduction of broodstock medaka Oryzias latipes (Temminck & Schlegel).

Here, we investigated the effect of dietary resveratrol (20, 40, and 80 µg/g BW/day) on cell-mediated immunity (activity of spleen phagocytes and proliferative response of lymphocytes) and reproductive parameters (egg and sperm quality, i.e. fecundity-total number of eggs produced by individual fish, fertility, embryo survival, and hatching rate) in medaka. Fish fed feed with resveratrol at 40 and 80 µg/g BW/day had significantly higher metabolic activity and intracellular phagocyte killing activity than control. The proliferative lymphocyte activity of the fish from R80 group was greater by more than 20 % in comparison with the control group (P < 0.05). The percentage of macrophages (MO) and their mean fluorescence intensities (MFI) in R40 and R80 groups were significantly higher compared to C and R20 groups (P < 0.05). The differences in MO and MFI values ranged from 52.5 % (±1.5; R0 group) to 65.8 % (±1.6; R80 group) and from 23.2 (±1.4; R0 group) to 38.2 (±2.4; R80 group), respectively. Moreover, resveratrol at 80 µg/g BW/day decreased liver COX activity, i.e. 5.4 in R80 group and 7.9 in R0 group (P < 0.05). The motility parameters of the sperm obtained from the males fed feed supplemented with resveratrol at 80 µg/g BW/day exhibited the highest values except the linearity, which was lower as compared to the control (P < 0.05). The results indicate that diet supplemented with resveratrol at a dosage of 40 µg/g BW/day improves phagocyte killing ability and lymphocyte proliferation in broodstock and accelerates offspring hatch. Also, the results suggest that COX activity influences sperm and oocyte quality in fish; the presence of a COX inhibitor in the dose of 40 µg/g BW/day decreased the embryo survival.

Propiscin--A safe anaesthetic for pikeperch (Sander Lucioperca L.).

The aim of this work was to determine the impact of etomidate (Propiscin) dose (1 and 2 ml l-1) and exposure time (2 and 10 min) on the biochemical and haematological parameters of juvenile pikeperch (Sander lucioperca) [mean body length (Lc) 25.9 cm; body weight (W) 189.9 g] that were reared in a recirculating aquaculture system (RAS). Significant changes in the mean values of total protein, globulin, calcium, magnesium, and ammonia were noted in all groups immediately following exposure. The greatest changes in the haematological indicators were observed in groups subjected to 10-min exposure at both doses of the anaesthetic. The specimens from these groups had higher values for white blood cells (WBC), red blood cells (RBC), haemoglobin (HGB), haematocrit (HCT), and mean corpuscular volume (MCV). Statistically significant differences in these same parameters were also noted in the groups of fish exposed to the anaesthetic for 2 min at a dose of 2 ml l-1, but they were not as pronounced. Twenty-four h following exposure to etomidate, all blood parameters in the experimental groups were comparable to those of the control group. Etomidate can be recommended as a safe, effective anaesthetic for pikeperch.

Cryopreservation of Acropora digitifera sperm with use of sucrose and methanol based solution.

Coral biodiversity has recently been considered an important topic in environmental studies. Biodiversity could be preserved with successful cryopreservation of endangered species gametes or embryos. Herein, we developed cryopreservation protocols for Acropora digitifera sperm with use of sucrose and methanol based extender. We studied cryopreservation of A. digitifera sperm with floating frames, allowing the placement of 250 µl French straws 4 cm above the liquid nitrogen surface, resulting in a 40 °C/min freezing rate. This method enabled the successful cryopreservation of sperm in 0.9 M sucrose supplemented with 20% methanol. In this protocol, we used a 1:3 (sperm:extender) dilution ratio. The fertilization ratios of freezing:thawed sperm were similar to the control and reached 63%. This method might be a valuable option in the formation of A. digitifera gene banking. Further studies are needed to explore possibilities of using this method in cryopreservation of other coral's sperm.