Post-translational processing leads to conformational changes in protein structure that modulate molecular functions and change the signature of metabolic transformations and immune responses. Some ...post-translational modifications (PTMs), such as phosphorylation and acetylation, are strongly related to oncogenic processes and malignancy. This study investigated a PTM pattern in patients with gender-specific ovarian or breast cancer. Proteomic profiling and analysis of cancer-specific PTM patterns were performed using high-resolution UPLC-MS/MS. Structural analysis, topology, and stability of PTMs associated with sex-specific cancers were analyzed using molecular dynamics modeling. We identified highly specific PTMs, of which 12 modified peptides from eight distinct proteins derived from patients with ovarian cancer and 6 peptides of three proteins favored patients from the group with breast cancer. We found that all defined PTMs were localized in the compact and stable structural motifs exposed outside the solvent environment. PTMs increase the solvent-accessible surface area of the modified moiety and its active environment. The observed conformational fluctuations are still inadequate to activate the structural degradation and enhance protein elimination/clearance; however, it is sufficient for the significant modulation of protein activity.
Early detection of microangiopathic complications of diabetes mellitus (DM) is necessary to analyze the patient's condition and prevent disease progression. The study was aimed to investigate the ...relationship between the presence of retinopathy and decreased reactivity of the microcirculatory bed in patients with diabetes.
The study involved 130 subjects: healthy volunteers (n = 48), DM patients without retinopathy (n = 53) and with retinopathy (n = 29). Skin microvascular reactivity was assessed on the forearm using laser Doppler flowmetry with a local heating test combined with occlusion.
The slope of local thermal hyperemia curve (Slope-120) and other parameters of microvascular reactivity showed difference in pairwise comparisons between the groups. Slope-120 had the highest sensitivity (0.759) and specificity (0.717) in detection of diabetic retinopathy. The decrease of Slope-120 was associated with retinopathy (odds ratio (OR) – 8.3 (2.9–24.1), p < 0.001), even after adjusting for other factors (OR – 11.0 (1.6–77.2), p = 0.016).
Thus, assessment of skin microvascular reactivity may be a useful test for detecting signs of microangiopathic complications and for screening patients in risk group. Decreased microvascular reactivity has been shown to be prospective as an independent indicator of retinopathy in type 1 DM.
•The diabetic microangiopathic changes occur in many organs and lead to complications.•The skin microcirculation can reflect signs of diabetes and diabetic complications.•In our study, decreased skin microvascular reactivity was associated with retinopathy.•It can be used as an independent risk factor for diabetic retinopathy presence.
Introduction
The development of new highly accurate, inexpensive and accessible methods for the detection of lower-extremity peripheral artery disease (LE-PAD) in diabetic patients is required. The ...aim of this study was to evaluate the accuracy of a new incoherent optical fluctuation flowmetry (IOFF) method in detecting legs with hemodynamically significant stenoses compared to ankle brachial index (ABI) and transcutaneous oximetry (TcPO2) in patients with diabetes mellitus (DM).
Materials and methods
Patients were recruited into 2 groups. Group 1 included patients with DM without LE-PAD and/or diabetic foot syndrome; Group 2 included patients with DM and LE-PAD. All patients underwent the following measurements: ultrasound (reference method), ABI, TcPO2, and the new IOFF method.
Results
The new IOFF method showed a sensitivity of 79.5% and a specificity of 89.8% in detecting limbs with hemodynamically significant stenosis (AUC 0.890, CI 0.822–0.957). TcpO2 allows the diagnosis of LE-PAD with 69.2% sensitivity and 86.2% specificity (AUC 0.817, CI 0.723–0.911). Using a standard ABI cut-off of less than 0.9, the sensitivity and specificity for this parameter were 34.5% and 89.7%, respectively. Increasing the diagnostic cut-off of the ABI on the study group to 0.99 improved sensitivity to 84.6% and specificity to 78% (AUC,0.824 CI 0.732–0.915).
Conclusions
The new IOFF technique has demonstrated high sensitivity and specificity in the detection of LE-PAD in patients with DM. The high accuracy, rapid measurement, and potential availability suggest that the new IOFF method has a high potential for clinical application in the detection of PAD.
This article describes the problems and prospects of introduction of electronic textbooks in the educational space of technical colleges. Practical recommendations for the maintenance, monitoring, ...organization and development of electronic textbooks projects.
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•Systematic approach realizes common features between related and unrelated diseases.•Neural network can use both meaningful and unassigned mass spectrometry-based data.•Convolutional ...neural network discriminates closely related phenotypes.•Neural network suggests comorbidity between schizophrenia and oncophenotypes.
The association between cancer risk and schizophrenia is widely debated. Despite many epidemiological studies, there is still no strong evidence regarding the molecular basis for the comorbidity between these two pathological conditions. The vast majority of assays have been performed using clinical records of schizophrenic patients or those undergoing cancer treatment and monitored for sufficient time to find shared features between the considered conditions. We performed mass spectrometry-based proteomic and metabolomic investigations of patients with different cancer phenotypes (breast, ovarian, renal, and prostate) and patients with schizophrenia. The resulting vast quantity of proteomic and metabolomic data were then processed using systems biology and one-dimensional (1D) convolutional neural network (1DCNN) machine learning approaches. Traditional systematic approaches permit the segregation of schizophrenia and cancer phenotypes on the level of biological processes, while 1DCNN recognized “signatures” that could segregate distinct cancer phenotypes and schizophrenia at the comorbidity level. The designed network efficiently discriminated unrelated pathologies with a model accuracy of 0.90 and different subtypes of oncophenotypes with an accuracy of 0.94. The proposed strategy integrates systematic analysis of identified compounds and application of 1DCNN model for unidentified ones to reveal the similarity between distinct phenotypes.
BACKGROUND: Neurogenic regulation is involved in the development of microcirculation response to local heating. We suggest that microvascular reactivity can be used to estimate the severity of ...diabetic polyneuropathy (DPN). OBJECTIVE: To evaluate the prospects for using the parameters of skin microvascular reactivity to determine the severity of DPN. METHODS: 26 patients with diabetes mellitus were included in the study (patients with retinopathy (n = 15), and without retinopathy (n = 11)). The severity of DPN was assessed using Michigan Neuropathy Screening Instrument (MNSI) and Norfolk QOL-DN (NQOLDN). Skin microcirculation was measured by laser Doppler flowmetry with local heating test. RESULTS: There were revealed moderate negative correlations between microvascular reactivity and the severity of DPN (for MNSI (Rs = –0.430), for NQOLDN (Rs = –0.396)). In patients with retinopathy, correlations were stronger than in the general group (for MNSI (Rs = –0.770) and NQOLDN (Rs = –0.636)). No such correlations were found in patients without retinopathy. CONCLUSION: Correlation of the microvascular reactivity and DPN was revealed in patients with registered structural disorders in microvessels (retinopathy). The lack of such correlation in patients without retinopathy may be explained by the intact compensatory mechanisms of microvessels without severe disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Activity coefficients at infinite dilution γ i ∞ of 19 alkanes, alkenes, and alkylbenzenes in the ionic liquid 4-methyl-n-butylpyridinium tetrafluoroborate (C10H16BF4N) were determined by gas ...chromatography using the ionic liquid as stationary phase. The measurements were carried out at different temperatures between 313.1 K and 363.1 K. From the temperature dependence of the limiting activity coefficients partial molar excess enthalpies at infinite dilution of the organic solutes in the ionic liquids have been derived.
Keloid scars, in contrast to other scar types, significantly reduce the patient's quality of life. To develop a nondestructive optical diagnostic technique predicting the keloid scars formation
, ...laser-induced fluorescence spectroscopy (LFS) was used to study the autofluorescence in skin of patients with various types of head and neck cicatricial deformities. The unexpected results were obtained for the endogenous fluorescence of lipofuscin. Significantly reduced autofluorescence of lipofuscin was registered both in the intact and in the keloid scar tissues in comparison with the intact and scar tissues in patients with hypertrophic and normotrophic scars. Sensitivity and specificity achieved by LFS in keloid diagnosis are 81.8% and 93.9% respectively. It could take place due to the changes in the reductive-oxidative balance in cells, as well as due to the proteolysis processes violation. Therefore, we suppose that the evaluation of the lipofuscin autofluorescence in skin before any surgical intervention could predict the probability of the subsequent keloid scars formation.
Laser fluorescence spectroscopy (LFS) is a potential tool for diagnosing pathological skin processes such as fibrosis, hypoxia, and inflammation. This article describes the results of the ...non-invasive assessment of skin autofluorescence for animals of different ages.
The study was performed on outbred white male mice (n = 14). Fluorescence spectra were measured using the multifunctional device LAKK-M (SPE Lazma, Moscow, Russia), which implements LFS in vivo. The method is to record the fluorescence spectrum of a tissue after laser irradiation at a wavelength of λe excites its fluorescence. The wavelength λe is selected corresponding to specific fluorophore properties. To excite the fluorescence, the wavelength λe = 535 nm was used, which made it possible to estimate the fluorescence intensity of the lipofuscin.
Increased autofluorescence of lipofuscin in the green waveband was detected in animals in the older age group compared to the younger group using LFS. It is important to note that the autofluorescence spectra of lipofuscin are in superposition with the spectra of other fluorophores and that the autofluorescence spectra of lipofuscin overlap the spectra of other fluorophores such as porphyrins. This may affect the interpretation of LFS data.
Adjustment of animal age is necessary for the optical assessment of pathological processes using LFS.
(1) Background: To date, there are no studies evaluating the ability of the incoherent optical fluctuation flowmetry (IOFF) method to assess foot tissue perfusion. The aim of this study was to ...evaluate the correlation between perfusion values measured by IOFF and TcPO2 in patients with diabetes-related lower-extremity complications. (2) Methods: This was an observational, cross-sectional, two-center study. Diabetic patients with peripheral artery disease and/or diabetic foot ulcers were studied (n = 27, examinations were carried out on 54 legs). Perfusion in the foot tissues was assessed using TcPO2 (reference standard for this study) and the IOFF method. (3) Results: High correlation coefficients of all perfusion parameters measured by IOFF with TcPO2 (Rs 0.7 to 0.76) were shown. The study demonstrated that the IOFF method allows, with a sensitivity of 85.7% and a specificity of 90.0%, the identification of patients with a critical decrease in TcPO2 < 20 mmHg. (4) Conclusions: The high correlation of IOFF parameters with TcPO2 and the moderately high sensitivity and specificity in detecting patients with severe ischemia of foot tissues shows the promise of the method for assessing a tissue perfusion in patients with diabetes-related lower-extremity complications.
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