The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer.

Bladder cancer is a common malignancy associated with high recurrence rates and potential progression to invasive forms. Sorafenib, a multi-targeted tyrosine kinase inhibitor, has shown promise in anti-cancer therapy, but its cytotoxicity to normal cells and aggregation in solution limits its clinical application. To address these challenges, we investigated the formation of supramolecular aggregates of sorafenib with Congo red (CR), a bis-azo dye known for its supramolecular interaction. We analyzed different mole ratios of CR-sorafenib aggregates and evaluated their effects on bladder cancer cells of varying levels of malignancy. In addition, we also evaluated the effect of the test compounds on normal uroepithelial cells. Our results demonstrated that sorafenib inhibits the proliferation of bladder cancer cells and induces apoptosis in a dose-dependent manner. However, high concentrations of sorafenib also showed cytotoxicity to normal uroepithelial cells. In contrast, the CR-BAY aggregates exhibited reduced cytotoxicity to normal cells while maintaining anti-cancer activity. The aggregates inhibited cancer cell migration and invasion, suggesting their potential for metastasis prevention. Dynamic light scattering and UV-VIS measurements confirmed the formation of stable co-aggregates with distinctive spectral properties. These CR-sorafenib aggregates may provide a promising approach to targeted therapy with reduced cytotoxicity and improved stability for drug delivery in bladder cancer treatment. This work shows that the drug-excipient aggregates proposed and described so far, as Congo red-sorafenib, can be a real step forward in anti-cancer therapies.

Mechanism of MyD88S mediated signal termination.

BACKGROUND: A universal adaptor protein, MyD88, orchestrates the innate immune response by propagating signals from toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R). Receptor activation seeds MyD88 dependent formation of a signal amplifying supramolecular organizing center (SMOC)-the myddosome. Alternatively spliced variant MyD88S, lacking the intermediate domain (ID), exhibits a dominant negative effect silencing the immune response, but the mechanistic understanding is limited. METHODS: Luciferase reporter assay was used to evaluate functionality of MyD88 variants and mutants. The dimerization potential of MyD88 variants and myddosome nucleation process were monitored by co-immunoprecipitation and confocal microscopy. The ID secondary structure was characterized in silico employing I-TASSER server and in vitro using nuclear magnetic resonance (NMR) and circular dichroism (CD). RESULTS: We show that MyD88S is recruited to the nucleating SMOC and inhibits its maturation by interfering with incorporation of additional components. Biophysical analysis suggests that important functional role of ID is not supported by a well-defined secondary structure. Mutagenesis identifies Tyr116 as the only essential residue within ID required for myddosome nucleation and signal propagation (NF-κB activation). CONCLUSIONS: Our results argue that the largely unstructured ID of MyD88 is not only a linker separating toll-interleukin-1 receptor (TIR) homology domain and death domain (DD), but contributes intermolecular interactions pivotal in MyD88-dependent signaling. The dominant negative effect of MyD88S relies on quenching the myddosome nucleation and associated signal transduction. Video abstract.

Personalized management of prostate cancer: from molecular and imaging markers to radiogenomics.

PURPOSE: Prostate cancer (PCa) is the second most common cancer in men. The urge to guide treatment tactics based on personal clinical risk factors has evolved in the era of human genome sequencing. To date, personalized approaches to managing PCa patients have not yet been developed. Radiogenomics is a relatively new term, used to refer to the study of genetic variation associated with imaging features of the tumour in order to improve the prognostication of the disease course. MATERIAL AND METHODS: The study is a review of recent knowledge regarding potential clinical applications of radiogenomics in personalized treatment of PCa. RESULTS: Recent investigations have proven that by combining data on individual genetic tumour features, and radiomic profiling (radiologic-molecular correlation), with traditional staging procedures in order to personalize treatment of PCa, an improved prognostication of PCa course can be performed, and overtreatment of indolent cancer can be avoided. It was found that a combination of multiparametric MRI and gene expression data allowed the detection of radiomic features of PCa, which correlated with a number of gene signatures associated with adverse outcomes. It was revealed that several molecular markers may drive tumour upstaging, allowed the distinction between the PCa stages, and correlated with aggressiveness-related radiomic features. CONCLUSIONS: The radiogenomics of PCa is not a comprehensively investigated area of oncourology. The combination of genomics and radiomics as integrative parts of precision medicine in the future has the potential to become the foundation for a personalized approach to the management of PCa.

Local recurrence of renal cell carcinoma after partial nephrectomy: applicability of the apparent diffusion coefficient of MRI as an imaging marker - a multicentre study.

Purpose: The goal of the study was an assessment of the diagnostic performance of diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) of magnetic resonance imaging (MRI) in distinguishing local recurrence (LR) of renal cell carcinoma (RCC) from benign conditions after partial nephrectomy. Material and methods: Thirty-nine patients after partial nephrectomy for solid RCC were enrolled in the study. Patients were followed up using MRI, which included DWI sequence (b = 800 s/mm2). All patients with MRI features of LR were included in the main group (n = 14) and patients without such features - into the group of comparison (n = 25). Apparent diffusion coefficient (ADC) values of suspicious lesions were recorded. In all patients with signs of locally recurrent RCC, surgical treatment was performed followed by pathologic analysis. Results: The mean ADC values of recurrent RCC demonstrated significantly higher numbers compared to benign fibrous tissues and were 1.64 ± 0.15 × 10-3 mm2/s vs. 1.02 ± 0.26 × 10-3 mm2/s (p < 0.001). The mean ADC values of RCCs' LR and benign post-op changes in renal scar substantially differed from mean ADC values of healthy kidneys' parenchyma; the latter was 2.58 ± 0.05 × 10-3 mm2/s (p < 0.001). In ROC analysis, the use of ADC with a threshold value of 1.28 × 10-3 mm2/s allowed us to differentiate local recurrence of RCC from benign postoperative changes with 100% sensitivity, 80% specificity, and accuracy: AUC = 0.980 (p < 0.001). Conclusions: The apparent diffusion coefficient of DWI of MRI can be used as a potential imaging marker for the diagnosis of local recurrence of RCC.

Chest Computed Tomography (CT) as a Predictor of Clinical Course in Coronavirus Disease.

BACKGROUND Chest imaging may be taken into consideration in detecting viral lung infections, especially if there are no tests available or there is a need for a prompt diagnosis. Imaging modalities enable evaluation of the character and extent of pulmonary lesions and monitoring of the disease course. The aim of this study was to verify the prognostic value of chest CT in COVID-19 patients. MATERIAL AND METHODS We conducted a retrospective review of clinical data and CT scans of 156 patients with SARS-CoV-2 infection confirmed by real-time reverse-transcription polymerase-chain-reaction (rRT-PCR) assay hospitalized in the Central Clinical Hospital of the Ministry of the Interior in Warsaw and in the Medical Centre in Lancut, Poland. The total severity score (TSS) was used to quantify the extent of lung opacification in CT scans. RESULTS The dominant pattern in discharged patients was ground-glass opacities, whereas in the non-survivors, the dominant pulmonary changes were consolidations. The non-survivors were more likely to have pleural effusion, pleural thickening, lymphadenopathy, air bronchogram, and bronchiolectasis. There were no statistically significant differences among the 3 analyzed groups (non-survivors, discharged patients, and patients who underwent prolonged hospitalization) in the presence of fibrotic lesions, segmental or subsegmental pulmonary vessel enlargement, subpleural lines, air bubble sign, and halo sign. CONCLUSIONS Lung CT is a diagnostic tool with prognostic utility in COVID-19 patients. The correlation of the available clinical data with semi-quantitative radiological features enables evaluation of disease severity. The occurrence of specific radiomics shows a positive correlation with prognosis.

Ischaemic background of brain fog in long-haul COVID-19 - a nuclear magnetic resonance spectroscopy-based metabonomic analysis. Preliminary results.

PURPOSE: Long-haul COVID-19 is a condition of unknown background occurring in COVID-19 survivors regardless of the severity of the SARS-CoV-2 infection itself. The aim of the study was to evaluate brain changes in patients suffering from variable symptoms of brain fog after COVID-19. MATERIAL AND METHODS: Eleven patients hospitalized due to symptoms of severe brain fog, i.e. insomnia, sudden impairment of cognitive function, headache, and depression, and 14 healthy volunteers underwent brain imaging including MR spectroscopy. RESULTS: Routine MR imaging revealed no specific macroscopic changes in keeping with brain fog. Considering that the clinical manifestation of brain fog is transient, the evaluation of the metabolic status of the brain remained the method of choice. The concentration of the major cerebral metabolites, i.e. NAA, Cho, and Cr, remained stable. However, changes in Glx and Lac concentration were observed in MR spectroscopy. CONCLUSIONS: Following results along with clinical course of the brain for imply probable ischaemic background of symptoms.

ESIPT-Related Origin of Dual Fluorescence in the Selected Model 1,3,4-Thiadiazole Derivatives.

In our previous work, we discussed the emergence of the dual fluorescence phenomenon in selected compounds from the group of 1,3,4-thiadiazoles. The results obtained in a number of experimental studies, supported by [TD]DFT calculations, clearly indicated that the phenomenon of dual fluorescence stemmed from an overlap of several factors, including the correct conformation of the analyzed molecule and, very significantly in this context, aggregation effects. Where those two conditions were met, we could observe the phenomenon of intermolecular charge transfer (CT) and the emergence of electronic states responsible for long wave emissions. However, in light of the new studies presented in this paper, we were able, for the first time, to provide a specific theory for the effect of dual fluorescence observed in the analyzed group of 1,3,4-thiadiazoles. We present the results of spectroscopic measurements conducted for two selected analogues from the 1,3,4-thiadiazole group, both in polar and non-polar solvents, which clearly evidence (as we have already suspected in the past, albeit have not shown in publications to date) the possibility of processes related to emission from the tautomer formed in the process of excited state intramolecular proton transfer, which is responsible for the long-wavelength emissions observed in the selected analogues. The presented results obtained with the use of UV-Vis, fluorescence (stationary and time-resolved), FTIR, and Raman spectroscopy, as well as from calculations of dipole moment changes between the ground and excited state with the use of two derivatives with different structures of the resorcylic system, corroborated our standing hypothesis. At the same time, they excluded the presence of ground state keto forms of the analyzed analogues unless necessitated by the structure of the molecule itself. In this case, aggregation factors enhance the observed effects related to the dual fluorescence of the analyzed compounds (by way of AIE-aggregated induced emissions).

Spectroscopic and Theoretical Studies of Fluorescence Effects in 2-Methylamino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole Induced by Molecular Aggregation.

The article presents the results of fluorescence analyses of 2-methylamino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (MDFT) in an aqueous environment. MDFT dissolved in aqueous solutions with a pH value in the range from 1 to 4.5 yielded an interesting effect of two clearly separated fluorescence emissions. In turn, a single fluorescence was observed in MDFT dissolved in water solutions with a pH value from 4.5 to 12. As it was suggested in the previous investigations of other 1,3,4-thiadiazole compounds, these effects may be associated with conformational changes in the structure of the analysed molecule accompanied by aggregation effects. Crystallographic data showed that the effect of the two separated fluorescence emissions occurred in a conformation with the -OH group in the resorcyl ring bound on the side of the sulphur atom from the 1,3,4-thiadiazole ring. The hypothesis of aggregation as the mechanism involved in the change in the spectral properties at low pH is supported by the results of (Time-Dependent) Density Functional Theory calculations. The possibility of rapid analysis of conformational changes with the fluorescence spectroscopy technique may be rather important outcome obtained from the spectroscopic studies presented in this article. Additionally, the presented results seem to be highly important as they can be easily observed in solutions and biologically important samples.

Spectroscopic Studies of Dual Fluorescence in 2-(4-Fluorophenylamino)-5-(2,4-dihydroxybenzeno)-1,3,4-thiadiazole: Effect of Molecular Aggregation in a Micellar System.

The article presents the results of spectroscopic studies focused on a selected compound from the 1,3,4-thiadiazole group-2-(4-fluorophenylamino)-5-(2,4-dihydroxybenzeno)-1,3,4-thia-diazole (FABT)-in a micellar system formed by Triton X-100, a non-ionic detergent. Fluorescence measurements revealed the phenomenon of dual fluorescence whose emergence is related to the particular molecular organisation of the compound, which depends both on the concentration of the detergent and, most of all, the concentration of the compound itself. Dual fluorescence of FABT in a micellar system was observed for the compound dissolved in a methanol aqueous system, i.e., an environment wherein the dual fluorescence of the compound had never been reported before. Based on the interpretation of UV-Vis electronic absorption, resonance light scattering (RLS), emission and excitation fluorescence spectra, as well as measurements of dynamic light scattering (DLS) and Principal Component Analysis (PCA), we were able to relate the occurrence of this effect to the process of molecular aggregation taking place between FABT molecules in the micellar system in question. Results of fluorescence spectra measurements and time-correlated single photon counting (TCSPC) indicate that dual fluorescence occurs at detergent concentrations necessary to form micellar systems, which in turn facilitate the process of aggregation of FABT molecules. The correlation between the observed fluorescence effects and the previous measurements performed for analogues from this group suggests the possibility of charge transfer (CT) within the range of detergent concentrations wherein the aforementioned fluorescence effects are observed. It ought to be emphasised that this type of fluorescence effects are relatively easy to induce, which predisposes this groups of fluorophores as ideal fluorescence probes in the context of biological samples.

Spectroscopic Studies of Fluorescence Effects in Bioactive 4-(5-Heptyl-1,3,4-Thiadiazol-2-yl)Benzene-1,3-Diol and 4-(5-Methyl-1,3,4-Thiadiazol-2-yl)Benzene-1,3-Diol Molecules Induced by pH Changes in Aqueous Solutions.

This paper presents the results of stationary fluorescence spectroscopy and time-resolved spectroscopy analyses of two 1,3,4-thiadiazole analogues, i.e. 4-(5-methyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (C1) and 4-(5-heptyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (C7) in an aqueous medium containing different concentrations of hydrogen ions. An interesting dual florescence effect was observed when both compounds were dissolved in aqueous solutions at pH below 7 for C1 and 7.5 for C7. In turn, for C1 and C7 dissolved in water at pH higher than the physiological value (mentioned above), single fluorescence was only noted. Based on previous results of investigations of the selected 1,3,4-thiadiazole compounds, it was noted that the presented effects were associated with both conformational changes in the analysed molecules and charge transfer (CT) effects, which were influenced by the aggregation factor. However, in the case of C1 and C7, the dual fluorescence effects were visible in a higher energetic region (different than that observed in the 1,3,4-thiadiazoles studied previously). Measurements of the fluorescence lifetimes in a medium characterised by different concentrations of hydrogen ions revealed clear lengthening of the excited-state lifetime in a pH range at which dual fluorescence effects can be observed. An important finding of the investigations presented in this article is the fact that the spectroscopic effects observed not only are interesting from the cognitive point of view but also can help in development of an appropriate theoretical model of molecular interactions responsible for the dual fluorescence effects in the analysed 1,3,4-thiadiazoles. Furthermore, the study will clarify a broad range of biological and pharmaceutical applications of these compounds, which are more frequently used in clinical therapies. Graphical Abstract Upper left corner - C7 molecule at high pH, right upper corner - fluorescence emission spectrum for C7 dissolved in H2O at high pH (7-12) - single fluorescence. Bottom left corner - C7 molecule at low pH (1-7), lower right corner - fluorescence emission spectrum for C7 dissolved in water at low pH - two fluorescence emissions. The circles indicate the group related to dissociation of molecules at low and high pH and the additional long circles indicate C1 or a molecule with a shorter acyl chain.

Intrinsic disorder of human Yin Yang 1 protein.

YY1 (Yin Yang 1) is a zinc finger protein with an essential role in various biological functions via DNA- and protein-protein interactions with numerous partners. YY1 is involved in the regulation of a broad spectrum of cellular processes such as embryogenesis, proliferation, tumorigenesis, and snRNA transcription. The more than 100 reported targets of the YY1 protein suggest that it contains intrinsically disordered regions that are involved in such diverse interactions. Here, we present a study of the structural properties of human YY1 using several biochemical and biophysical techniques (fluorescence, circular dichroism, gel filtration chromatography, proteolytic susceptibility) together with various bioinformatics approaches. To facilitate our exploration of the YY1 structure, the full-length protein as well as an N-terminal fragment (residues 1-295) and the C-terminal DNA binding domain were used. We found the N-terminus to be a non-compact fragment of YY1 with little residual secondary structure and lacking a well-defined tertiary structure. The results of our study indicate that YY1 belongs to the family of intrinsically disordered proteins (IDPs), which exist natively in a partially unfolded conformation.

Influence of Solvent Polarizability on the Keto-Enol Equilibrium in 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl]benzene-1,3-diol.

This work presents spectroscopic studies of the keto-enol equilibrium induced by solvent polarizability in 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl]benzene-1,3-diol a strong antiproliferative and anticancer thiadiazol derivative. Electronic absorption, steady state and time resolved fluorescence, and infrared spectroscopies were applied to investigate the keto and enol forms of this compound in a series of polar and non-polar solvents. The enol form dominates in polar solvents while, surprisingly, the keto form dominates in non-polar solvents with high average electric dipole polarizability e.g. n-alkenes. The electronic absorption spectrum of this derivative is more dependent on spatially averaged electric dipole polarizability of the solvent than on Kirkwood's correlation or on Lorenz-Lorenz electric polarizability. By analogy of n-alkanes to the alkyl parts of lipids, one can expect that the transformation of 1,3,4-thiadiazoles to the keto form may be facilitated in the hydrophobic core of the lipid membrane. Such a transition may be of great practical importance for the design of biologically active pharmaceutics, which are able to interact with the hydrophobic regions of cell membranes in a specific manner.

Spectroscopic Studies of Dual Fluorescence in 2-((4-Fluorophenyl)amino)-5-(2,4-dihydroxybenzeno)-1,3,4-thiadiazole.

The paper presents results of fluorescence analysis of ionic and nonionic 2-((4-fluorophenyl)amino)-5-(2,4-dihydroxybenzeno)-1,3,4-thiadiazole (FABT) in monocrystals and solutions. We found a single fluorescence band in the case of FABT crystals grown in methanol and dual fluorescence for FABT crystals grown in an aqueous environment. The effect of dual fluorescence was preserved for FABT dissolved in aqueous solutions with pH ranging from 7.5 to 1. In contrast, FABT dissolved in methanol exhibited a single fluorescence band. The dual fluorescence effect is associated with conformational changes in the FABT molecule, which can be induced by aggregation effects. On the basis of crystallographic data, two types of FABT crystal molecule conformations were distinguished. In methanol, FABT molecules are in conformation "S" (the -OH group from the resorcyl ring oriented toward the sulfur atom from the 1,3,4-thiadiazole ring), which a gives single fluorescence band. In water, FABT in conformation "N" (the -OH group from the resorcyl ring oriented toward the nitrogen atom from the 1,3,4-thiadiazole ring due to 180° rotation) has two fluorescence bands. This significant finding implies the possibility of performing a rapid analysis of conformational changes in FABT molecules using fluorescence spectroscopy both in solutions and in biological samples.

The time effectiveness of three-dimensional telediagnostic postural screening of back curvatures and scoliosis.

BACKGROUND: Postural screening remains a powerful tool that can be used to identify children and adolescents with scoliosis or sagittal plane deformities. The aim of this study was to assess the time effectiveness of implemented telediagnostic screening procedures. MATERIALS AND METHODS: Medical images (virtual objects) of acquired clouds of points of 100 subjects of both sexes were chosen at random from the database and used for parametric evaluation for this study. This study was performed using a newly developed three-dimensional (3D) back surface topography measurement system for posture and scoliosis using a structured light method. The duration of each step of therapist/nurse/physician-assisted 3D assessment was measured independently with a stopwatch. Two configurations of PC computers and Internet connections were used to test the time effectiveness. Scoliotic postures were detected using cutoff values of angle of trunk rotation, Posterior Trunk Symmetry Index, and Deformity in the Axial Plane Index indices. RESULTS: The overall assessment of all subjects consumed from 2 h 55 min 55 s to 3 h 18 min 59 s dependent on PC and Internet connection configuration. Average examination time per subject ranged from 2 min 43 s to 4 min 51 s, respectively. The virtual landmarking and report generation times were dependent on the PC configuration (p<0.001). Our study confirmed satisfactory time effectiveness of the implemented telediagnostic postural screening procedure. We assume that it may influence the cost-effectiveness of the screening, which is usually mentioned as an important factor for recommendations against postural school screening. Relatively fast Internet connection and a medium-level PC configuration are sufficient for achieving a reasonably short time of 3D posture assessment of a virtual object representing a real subject's back surface. CONCLUSIONS: The efficiency of remote assessment of exact 3D surface topography can be used in large-scale studies for posture and scoliosis epidemiology.

Solitary fibrous tumour of the pleura - cases analysis.

BACKGROUND: Isolated fibrous tumor of the pleura (SFTP - Solitary fibrous tumour of the pleura/localized fibrous tumour of the pleura) is a rare primary tumour of the pleura of mesenchymal origin. In most cases, it is a benign lesion. It is composed of spindle cells similar to fibroblasts and derives probably from submesothelial mesenchyme. The aim of the study was to analyze clinical symptoms, incidence, possibility of suggesting the diagnosis on the basis of imaging tests, and confirmation of the diagnosis in pathological tests with regard to studies of histochemistry examination. MATERIAL/METHODS: Clinical and morphological material obtained from 14 patients from Department of Thoracic Surgery of Subcarpathian Chest Disease Center treated between year 2004 and 2010 was analysed. In the first stage, selected cases of patients with isolated fibrous tumour of the pleura were chosen from the archives and the analysis of their medical history was carried out. Basic information about age, gender, medical history, smoking habit, physical examination and results of imaging, endoscopic and morphological examinations were noted. The second parallel component of the study was pathomorphological examinations of the surgical material obtained from the patients, including the assessment of morphology and immunohistochemistry. RESULTS: Of the 14 examined patients, fibrous tumour occurred in 8 men and 6 women. The age range of the patients was 37-73 years, with a peak attributable to the 6(th) decade of life. In 8 patients the tumour was detected incidentally during routine examinations. In 7 patients there were no clinical signs of respiratory disease, and if present, then the most common complaint was shortness of breath. Regarding symptoms not connected with the respiratory system, anemia occurred most frequently. Fibrous tumour of the pleura was more often associated with the visceral pleura than with the parietal pleura. The largest lesion was approximately 20 cm in size. CONCLUSIONS: Fibrous tumour of the pleura is a pleura-based neoplasm which is usually detected incidentally, and is often asymptomatic or poorly symptomatic. Computed tomography imaging allows to suggest a correct diagnosis. Histopathological diagnosis is based on immunohistochemical examinations.

Zinc Ions Modulate YY1 Activity: Relevance in Carcinogenesis.

YY1 is widely recognized as an intrinsically disordered transcription factor that plays a role in development of many cancers. In most cases, its overexpression is correlated with tumor progression and unfavorable patient outcomes. Our latest research focusing on the role of zinc ions in modulating YY1's interaction with DNA demonstrated that zinc enhances the protein's multimeric state and affinity to its operator. In light of these findings, changes in protein concentration appear to be just one element relevant to modulating YY1-dependent processes. Thus, alterations in zinc ion concentration can directly and specifically impact the regulation of gene expression by YY1, in line with reports indicating a correlation between zinc ion levels and advancement of certain tumors. This review concentrates on other potential consequences of YY1 interaction with zinc ions that may act by altering charge distribution, conformational state distribution, or oligomerization to influence its interactions with molecular partners that can disrupt gene expression patterns.

Sulfhemoglobin under the spotlight - Detection and characterization of SHb and HbFeIII-SH.

Sulfhemoglobinemia is an incurable disease caused by an overdose of sulfur-containing drugs with oxidizing properties. Its diagnosis remains hindered due to the similarity of symptoms to other pathological state - methemoglobinemia, as well as contradictory information on the structure and characteristics of sulfhemoglobin. Herein, we present sulfhemoglobinemia model on living functional human erythrocytes, designed to recreate processes which could take place in a patient body in order to complement missing information and highlight distinctiveness of two hemoglobin (Hb) adducts formed after interaction with sulfur donors. Employed techniques, UV-Vis absorption, Raman, Fourier transformed infrared (FT-IR) and electronic circular dichroism (ECD) spectroscopies, allowed to distinguish and characterize Hb adduct with sulfur atom bounded directly to the iron ion (HbFeIII-SH), and irreversibly connected to the porphyrin ring (SHb - sulfhemoglobin). Presented herein results provided also new evidence on formation of both these hemoglobin adducts inside functional erythrocytes under oxidative conditions and during sulfur-containing drug presence, what can be further translated into future physiological studies. Moreover, we found that sulfur attachment to the porphyrin ring altered Hb structure and lead to changes in protein packing inside RBCs, eventually. Interestingly, measurement of blood drop smear by Raman spectroscopy occurred the most accurate method to differentiate HbFeIII-SH and SHb, indicating potential of this technique in sulfhemoglobinemia diagnosis.

Zinc controls operator affinity of human transcription factor YY1 by mediating dimerization via its N-terminal region.

Human protein Yin Yang 1 (YY1) controls the transcription of hundreds of genes both positively and negatively through interactions with a wide range of partner proteins. Results presented here from proteolytic sensitivity, calorimetry, circular dichroism, fluorescence, NMR, size-exclusion chromatography, SELEX, and EMSA show that purified YY1 forms dimers via its disordered N-terminal region with strong zinc-ion concentration dependence. The YY1 dimer is shown to bind tandem repeats of a canonical recognition DNA sequence with high affinity, and analysis of human YY1 regulatory sites shows that many contain repeats of its recognition elements. YY1 dimerization may compete with partner protein interactions, making control by zinc ion concentration a previously unrecognized factor affecting YY1 gene regulation. Indeed, YY1 is known to be important in many pathogenic processes, including neoplasia, in which zinc ion concentrations are altered. The present results incentivize studies in vivo or in vitro that explore the role of zinc ion concentration in YY1-mediated gene expression.

Telediagnostic 3D school screening of back curvatures and posture using structured light method - pilot study.

BACKGROUND: Several studies consider the school scoliosis screening as controversial. Many authors postulate to improve its clinical effectiveness. AIM: Authors assumed that three dimensional telediagnostic surface topography measurements allowing measuring several postural deformity indexes and angles of curvatures in sagittal plane may enhance current practice. The study was designed to determine usefulness of school screening back evaluation performed utilizing the three dimensional telediagnostic measurement system. METHODS: The measurement module is based on structured light method using "3D Orthoscreen" system. The technique for 3D image acquisition of back shape is based on temporal phase shifting and Gray codes. Measurement data was securely archived for remote access by investigator over the secure Internet connection. Acquired "images" were transferred to Telediagnostic Center for clinical evaluation. Spine parameters and deformation indexes like Posterior Trunk Symmetry Index (POTSI), Deformity in the Axial Plane Index (DAPI), kyphosis and lordosis angle were measured. The preliminary study was performed in 2 selected schools (basic and middle schools). The study was approved by Bioethical Committee. Clouds of points representing back topography of assessed subjects were acquired at schools in March and May 2011 and stored for remote evaluation and analysis. RESULTS: 758 children averagely aged 11.1 years (from 5 to 16), 387 females and 371 males, were examined. Their average body mass was 45.13 kg [16-105; STD 16.4] and average height was 151.43 cm, [110-192; STD 18.3]. The average values of back assessment parameters were as follows: POTSI 15.97% [0-73.4; STD 10.3]; DAPI 0.88% [0-5.9; STD 0.76]; kyphosis angle 10.19° [0-32; STD 5.82]; and lordosis angle 32,82° [0-56; STD 9.86]. CONCLUSION: Technical and clinical issues of the practical implementation allowed to elaborate preliminary protocol for cohort studies addressed to subject (i.e. parents acceptance of examination of undressed back) and technical issues (i.e. upload data and retrieval, network transfer velocity). Postural telediagnostics was found sufficiently feasible for further implementation of remote, cohort 3D back shape evaluations including school screening. Permanently saved 3D data allow monitoring back surface of the individual subjects.

Diagnostic value of chest CT scanning for determination of Covid-19 severity in individual lung lobes.

INTRODUCTION AND OBJECTIVE: CT examination is an important diagnostic tool in assessment of the severity of the infection and course of the disease. The aim of the study was to evaluate the degree and frequency of involvement of individual lung lobes and the population Lobe Involvement Coefficient (pLIC) value in the investigated population. MATERIAL AND METHODS: The analyzed material comprised 124 patients aged 18-92 years. CT examinations were performed using a 16- and 32-row CT LightSpeed apparatus. The spatial distribution of typical Covid -19 pathological changes was analyzed, divided into five lung lobes. The degree of the severity of lobe involvement was assessed using counters and percentages, as well as the population Lobe Involvement Coefficient (pLIC). Statistical analysis of data was performed with the use of Statistica 10.0 software. Values were measured on an oridinal scale. Anova Friedman's test was used to compare lobes. RESULTS: Statistically significant differences in the involvement between most of the individual lobes were shown. There was no statistically significant difference in the degree of lobe involvement between the left and right upper lobes, nor in the left and right lower lobes. The highest pILC was demonstrated for the lower lobe and the lowest value was obtained for the middle lobe. CONCLUSIONS: The lower lobes were affected most frequently and most severely, with no statistical difference between the right and left sides. The middle lobe was affected relatively least frequently and lightly. The introduced pLIC index allows quantitative assessment of individual lobes involvement in relation to the entire studied population.