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Spectrochimica Acta. Part A, Molecular... Nov 2023The present study focuses on structural and chemical analyses of N-phenylmorpholine-4-carboxamide benzene-1,2-diamine (PMCBD) using quantum computational methods. The...
The present study focuses on structural and chemical analyses of N-phenylmorpholine-4-carboxamide benzene-1,2-diamine (PMCBD) using quantum computational methods. The calculated bond angle, length, and dihedral angle between atoms were compared with measured values. The observed and stimulated FT-IR (Fourier Transform Infrared Spectroscopy) spectra parameters for vibrational wavenumbers and their associated PED (Potential Energy Distribution) values in percentage have been obtained from VEDA4 software. The electronic transitions of PMCBD were discussed by TD-SCF/DFT/B3LYP based on the 6-311++G(d,p) basis set with solvents such as chloroform, ethanol, and dimethyl sulfoxide (DMSO) and gas. Density functional computations were used to study the band energy between HOMO and LUMO using the B3LYP/6-311++G(d,p) level. Mulliken analysis and natural population analysis were used for a better understanding of charge levels on different atoms such as N, H and O. The natural bonding orbital (NBO) analysis proved helpful in studying molecular and bond strengths. (NBO). The ESP acquired data on the molecule's size, shape, charge density distribution, and chemical reactivity site. This was done by mapping electron density on the surface with electrostatic potential. Non-linear optical detection of PMCBD was also discussed. Aside from the electron localization function map, state densities are also mapped using Multiwfn software, a wave function analyzer.
Topics: Models, Molecular; Molecular Conformation; Spectroscopy, Fourier Transform Infrared; Benzene; Spectrum Analysis, Raman; Diamines; Static Electricity; Quantum Theory; Thermodynamics; Vibration; Spectrophotometry, Ultraviolet
PubMed: 37321138
DOI: 10.1016/j.saa.2023.122988 -
European Journal of Nuclear Medicine... Jan 2024Standardized uptake value (SUV) has been prevalently used to measure [ Ga]Ga-PSMA-11 activity in prostate cancer, but it is susceptible to multiple factors. Parametric...
PURPOSE
Standardized uptake value (SUV) has been prevalently used to measure [ Ga]Ga-PSMA-11 activity in prostate cancer, but it is susceptible to multiple factors. Parametric imaging allows for absolute quantification of tracer uptake and provides a better diagnostic accuracy that is crucial for lesion detection. However, the clinical significance of total-body parametric imaging of [ Ga]Ga-PSMA-11 remains to be fully assessed. Therefore, the aim of our study is to delve into the diagnostic implications of total-body parametric imaging of [ Ga]Ga-PSMA-11 PET/CT for patients with prostate cancer.
METHODS
Twenty prostate cancer patients were included and underwent a dynamic total-body [ Ga]Ga-PSMA-11 PET/CT scan. An irreversible two-tissue compartment model (2T3k) was fitted for each tissue time-to-activity curve, and the net influx rate (K) was obtained. The image quality and semi-quantitative analysis of lesion-to-background ratio (LBR), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were compared between parametric images and SUV images.
RESULTS
Kinetic modeling using 2T3k demonstrated favorable model fitting in both normal organs and lesions. All of the lesions detected on SUV images (55-60 min) could be detected on K images. The correlation between K, SUV and SUV in both normal organs and pathological lesions was found to be positive and statistically significant. Conversely, a moderate positive correlations were found between K and K (R = 0.69, P < 0.001; R = 0.61, P < 0.001) and K and k (R = 0.69, P < 0.001; R = 0.62, P < 0.001), in normal organs and pathological lesions, respectively. Visual assessment in K images showed less image noise and higher lesions conspicuity compared to SUV images. K image-derived LBR, SNR, and CBR of pathological lesions including primary tumors (PTs), lymph node metastases (LNMs) and bone metastases (BMs), exhibited remarkably higher folds (1.4-3.6 folds) compared to those derived from SUV of corresponding lesions.
CONCLUSIONS
Total-body parametric imaging of [ Ga]Ga-PSMA-11 enhanced lesion contrast and improved lesion detectability compared to SUV images. This may potentially serve as an imaging biomarker and theranostic tool for precise diagnosis and treatment evaluation in prostate cancer patients.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Gallium Radioisotopes; Prostatic Neoplasms; Edetic Acid
PubMed: 37792025
DOI: 10.1007/s00259-023-06456-1 -
Clinical Nuclear Medicine Jan 202468 Ga-prostate specific membrane antigen (PSMA) PET/CT scan for staging revealed increased 68 Ga-PSMA uptake in solar elastosis in a patient with prostate cancer. Solar...
68 Ga-prostate specific membrane antigen (PSMA) PET/CT scan for staging revealed increased 68 Ga-PSMA uptake in solar elastosis in a patient with prostate cancer. Solar elastosis is a degenerative condition of elastic tissue in the dermis caused by prolonged sun exposure. A few studies have demonstrated 68 Ga-PSMA uptake in cutaneous lesions. This case illustrates another instance of a benign cutaneous lesion accompanied by increased 68 Ga-PSMA uptake.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Gallium Radioisotopes; Prostatic Neoplasms; Skin Diseases; Edetic Acid
PubMed: 38015624
DOI: 10.1097/RLU.0000000000004967 -
Clinical Nutrition (Edinburgh, Scotland) Mar 2024The aim of this study is using clinical factors and non-enhanced computed tomography (CT) deep features of the psoas muscles at third lumbar vertebral (L3) level to...
OBJECTIVE
The aim of this study is using clinical factors and non-enhanced computed tomography (CT) deep features of the psoas muscles at third lumbar vertebral (L3) level to construct a model to predict malnutrition in gastric cancer before surgery, and to provide a new nutritional status assessment and survival assessment tool for gastric cancer patients.
METHODS
A retrospective analysis of 312 patients of gastric cancer were divided into malnutrition group and normal group based on Nutrition Risk Screening 2002(NRS-2002). 312 regions of interest (ROI) of the psoas muscles at L3 level of non-enhanced CT were delineated. Deep learning (DL) features were extracted from the ROI using a deep migration model and were screened by principal component analysis (PCA) and least-squares operator (LASSO). The clinical predictors included Body Mass Index (BMI), lymphocyte and albumin. Both deep learning model (including deep learning features) and mixed model (including selected deep learning features and selected clinical predictors) were constructed by 11 classifiers. The model was evaluated and selected by calculating receiver operating characteristic (ROC), area under curve (AUC), accuracy, sensitivity and specificity, calibration curve and decision curve analysis (DCA). The Cohen's Kappa coefficient (κ) was using to compare the diagnostic agreement for malnutrition between the mixed model and the GLIM in gastric cancer patients.
RESULT
The results of logistics multivariate analysis showed that BMI [OR = 0.569 (95% CI 0.491-0.660)], lymphocyte [OR = 0.638 (95% CI 0.408-0.998)], and albumin [OR = 0.924 (95% CI 0.859-0.994)] were clinically independent malnutrition of gastric cancer predictor(P < 0.05). Among the 11 classifiers, the Multilayer Perceptron (MLP)were selected as the best classifier. The AUC of the training and test sets for deep learning model were 0.806 (95% CI 0.7485-0.8635) and 0.769 (95% CI 0.673-0.863) and with accuracies were 0.734 and 0.766, respectively. The AUC of the training and test sets for the mixed model were 0.909 (95% CI 0.869-0.948) and 0.857 (95% CI 0.782-0.931) and with accuracies of 0.845 and 0.861, respectively. The DCA confirmed the clinical benefit of the both models. The Cohen's Kappa coefficient (κ) was 0.647 (P < 0.001). Diagnostic agreement for malnutrition between the mixed model and GLIM criteria was good. The mixed model was used to calculate the predicted probability of malnutrition in gastric cancer patients, which was divided into high-risk and low-risk groups by median, and the survival analysis showed that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P = 0.005).
CONCLUSION
Deep learning based on mixed model may be a potential tool for predicting malnutrition in gastric cancer patients.
Topics: Humans; Stomach Neoplasms; Deep Learning; Retrospective Studies; Malnutrition; Albumins; Tomography; Benzamides; Phenylenediamines
PubMed: 38377634
DOI: 10.1016/j.clnu.2024.02.005 -
Fluids and Barriers of the CNS Dec 2023The lack of accessible and informative biomarkers results in a delayed diagnosis of Parkinson's disease (PD), whose symptoms appear when a significant number of...
BACKGROUND
The lack of accessible and informative biomarkers results in a delayed diagnosis of Parkinson's disease (PD), whose symptoms appear when a significant number of dopaminergic neurons have already disappeared. The retina, a historically overlooked part of the central nervous system (CNS), has gained recent attention. It has been discovered that the composition of cerebrospinal fluid influences the aqueous humor composition through microfluidic circulation. In addition, alterations found in the brain of patients with PD have a correlate in the retina. This new paradigm highlights the potential of the aqueous humor as a sample for identifying differentially concentrated metabolites that could, eventually, become biomarkers if also found altered in blood or CSF of patients. In this research we aim at analyzing the composition of the aqueous humor from healthy controls and PD patients.
METHODS
A targeted metabolomics approach with concentration determination by mass spectrometry was used. Statistical methods including principal component analysis and linear discriminants were used to select differentially concentrated metabolites that allow distinguishing patients from controls.
RESULTS
In this first metabolomics study in the aqueous humor of PD patients, elevated levels of 16 compounds were found; molecules differentially concentrated grouped into biogenic amines, amino acids, and acylcarnitines. A biogenic amine, putrescine, alone could be a metabolite capable of differentiating between PD and control samples. The altered levels of the metabolites were correlated, suggesting that the elevations stem from a common mechanism involving arginine metabolism.
CONCLUSIONS
A combination of three metabolites, putrescine, tyrosine, and carnitine was able to correctly classify healthy participants from PD patients. Altered metabolite levels suggest altered arginine metabolism. The pattern of metabolomic disturbances was not due to the levodopa-based dopamine replacement medication because one of the patients was not yet taking levodopa but a dopamine receptor agonist.
Topics: Humans; Parkinson Disease; Levodopa; Aqueous Humor; Putrescine; Biomarkers; Arginine
PubMed: 38049870
DOI: 10.1186/s12987-023-00494-5 -
Current Pharmaceutical Design 2024Digital PCR (dPCR) is the latest technique that has become commercially accessible for various types of research. This method uses Taq polymerase in a standard... (Review)
Review
Digital PCR (dPCR) is the latest technique that has become commercially accessible for various types of research. This method uses Taq polymerase in a standard polymerase chain reaction (PCR) to amplify a target DNA fragment from a complex sample, like quantitative PCR (qPCR) and droplet digital PCR (dd- PCR). ddPCR may facilitate microRNA (miRNA) measurement, particularly in liquid biopsy, because it has been proven to be more effective and sensitive, and in this method, ddPCR can provide an unprecedented chance for deoxyribonucleic acid (DNA) methylation research because of its capability to increase sensitivity and precision over conventional PCR-based methods. qPCR has also been found to be a valuable standard technique to measure both copy DNA (cDNA) and genomic DNA (gDNA) levels, although the finding data can be significantly variable and non-reproducible without relevant validation and verification of both primers and samples. The SYBR green quantitative real-time PCR (qPCR) method has been reported as an appropriate technique for quantitative detection and species discrimination, and has been applied profitably in different experiments to determine, quantify, and discriminate species. Although both TaqMan qRT-PCR and SYBR green qRT-PCR are sensitive and rapid, the SYBR green qRT-PCR assay is easy and the TaqMan qRT-PCR assay is specific but expensive due to the probe required. This review aimed to introduce dPCR, qPCR, SYBR green PCR kit, and digital PCR, compare them, and also introduce their advantages in the detection of different diseases.
Topics: Humans; Real-Time Polymerase Chain Reaction; Benzothiazoles; Diamines; DNA; Quinolines
PubMed: 38243947
DOI: 10.2174/0113816128276560231218090436 -
Scientific Reports Feb 2024Ferroptosis plays an important role in inflammation and oxidative stress. Whether ferroptosis is involved in the inflammation of vascular endothelial cells and its...
Ferroptosis plays an important role in inflammation and oxidative stress. Whether ferroptosis is involved in the inflammation of vascular endothelial cells and its regulation mechanism remains unclear. We estimated the correlation between serum iron ion levels and the inflammation index of 33 patients with arteriosclerosis. In vitro, HUVECs with or without ferrostatin-1 were exposed to Lipopolysaccharide. Corresponding cell models to verify the target signaling pathway. The results showed that serum iron ion levels had a significant positive correlation with N ratio, N/L, LDL level, and LDL/HDL (P < 0.05), and a negative correlation with L ratio (P < 0.05) in the arteriosclerosis patients. In vitro, ferroptosis is involved in HUVECs inflammation. Ferrostatin-1 can rescue LPS-induced HUVECs inflammation by decreasing HMGB1/IL-6/TNF-α expression. Nrf2 high expression could protect HUVECs against ferroptosis by activating the GPX4/GSH system, inhibiting ferritinophagy, and alleviating inflammation in HUVECs by inhibiting HMGB1/IL-6/TNF-α expression. It also found that Nrf2 is a key adaptive regulatory factor in the oxidative damage of HUVECs induced by NOX4 activation. These findings indicated that ferroptosis contributed to the pathogenesis of vascular endothelial cell damage by mediating endothelial cell inflammation. Nrf2-mediated redox balance in vascular inflammation may be a therapeutic strategy in vascular diseases.
Topics: Humans; Endothelial Cells; Ferroptosis; HMGB1 Protein; Interleukin-6; Lipopolysaccharides; NF-E2-Related Factor 2; Tumor Necrosis Factor-alpha; Inflammation; Oxidation-Reduction; Arteriosclerosis; Iron; Cyclohexylamines; Phenylenediamines
PubMed: 38336964
DOI: 10.1038/s41598-024-53976-3 -
Scientific Reports Jul 2023A one-step sandwich chemiluminescence immunometric assay (LIA) was developed for the quantification of bifunctional peptidylglycine-α-amidating monooxygenase (PAM) in...
A one-step sandwich chemiluminescence immunometric assay (LIA) was developed for the quantification of bifunctional peptidylglycine-α-amidating monooxygenase (PAM) in human plasma (PAM-LIA). PAM is responsible for the activation of more than half of known peptide hormones through C-terminal α-amidation. The assay employed antibodies targeting specific catalytic PAM-subunits, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), to ensure detection of full-length PAM. The PAM-LIA assay was calibrated with a human recombinant PAM enzyme and achieved a detection limit of 189 pg/mL and a quantification limit of 250 pg/mL. The assay demonstrated good inter-assay (6.7%) and intra-assay (2.2%) variabilities. It exhibited linearity when accessed by gradual dilution or random mixing of plasma samples. The accuracy of the PAM-LIA was determined to be 94.7% through spiking recovery experiments, and the signal recovery after substance interference was 94-96%. The analyte showed 96% stability after six freeze-thaw cycles. The assay showed strong correlation with matched EDTA and serum samples, as well as matched EDTA and Li-Heparin samples. Additionally, a high correlation was observed between α-amidating activity and PAM-LIA. Finally, the PAM-LIA assay was successfully applied to a sub-cohort of a Swedish population-based study, comprising 4850 individuals, confirming its suitability for routine high throughput screening.
Topics: Humans; Edetic Acid; Mixed Function Oxygenases; Multienzyme Complexes
PubMed: 37402878
DOI: 10.1038/s41598-023-37976-3 -
Current Eye Research Nov 2023This study was designed to determine if previous approaches to eliminate fibroblast contamination in different cells types would be successful in eliminating fibroblast...
PURPOSE
This study was designed to determine if previous approaches to eliminate fibroblast contamination in different cells types would be successful in eliminating fibroblast contamination from human and mouse primary corneal epithelial cell cultures, with the primary goal being to describe a simple, easy, and effective method to culture fibroblast-free primary mouse and human corneal epithelial cell cultures.
METHODS
Primary human and mouse corneal stromal cells and epithelial cells were isolated and cultured from human corneal rims and mouse corneas, respectively. Several approaches previously used in other tissue types were evaluated using corneal epithelial cells and mixtures of fibroblasts and epithelial cells to determine the most effective purification method. Methods evaluated included 0.25% trypsin-EDTA, low temperature, mitomycin-C, and dispase. Degree of fibroblast contamination was examined using light microscopy evaluation of cell phenotype, immunofluorescence and western blotting using cell type-specific markers. Anti-pancytokeratin (PanCK) was used as the epithelial immunofluorescence label, and anti-α smooth muscle actin (αSMA) as the fibroblast immunofluorescence label. Epithelial western blot antibodies included PanCK, keratin 12, and E-cadherin, while αSMA, collagen 1A1 and collagen 3A1 were used to identify fibroblasts.
RESULTS
Fibroblast contamination of human and mouse primary cornea epithelial cell cultures was best controlled using the 0.25% trypsin-EDTA method. The other methods examined were not effective at eliminating cornea fibroblast contamination.
CONCLUSIONS
Trypsin-EDTA digestion is a simple and effective method for controlling fibroblast contamination of cultured primary human and mouse corneal epithelial cells.
Topics: Humans; Animals; Mice; Edetic Acid; Trypsin; Cells, Cultured; Cornea; Epithelial Cells; Fibroblasts; Collagen
PubMed: 37490619
DOI: 10.1080/02713683.2023.2241683 -
Experimental Dermatology Sep 2023Wound fluid has been well studied for exploring protein biomarkers contained in it. However, cells in wound fluid have not received much attention due to the difficulty...
Wound fluid has been well studied for exploring protein biomarkers contained in it. However, cells in wound fluid have not received much attention due to the difficulty in their collection. Our study aimed to establish a method for collecting viable cells from discarded wound dressings. A protocol was designed to wash out nonadherent cells and detach adherent cells from silicone-faced foam wound dressings using trypsin-EDTA. The optimal concentration and incubation time of trypsin-EDTA for collecting equivalent proportions of different cell types to the original cell population were determined in vitro. Cell composition and gene expression changes in monocytes, lymphocytes, neutrophils, fibroblasts and keratinocytes were confirmed using immunocytochemistry and RNA-sequencing ex vivo. Full-thickness wounds were created on 9-week-old male C57BL/6J mice. Wound fluid was collected, and half of it was applied to the wound dressings. The original cell population in the wound fluid and the cell population collected from wound dressings were compared. In the in vitro study, 0.25% trypsin-EDTA and 2.5-min incubation time were considered optimal for collecting adherent cells from wound dressings. In the ex vivo study, among all cell types, only CD3+ lymphocytes showed a significantly higher cell proportion in the collected group. The relative gene expression of the five selected cells showed no significant changes (p-value >0.05, |log fold change| < 1.5, differential gene expression analysis). Viable nonadherent and adherent cells were collected from wound dressings without altering gene expression and could be used in future studies for cellular analysis of wound fluid.
Topics: Animals; Mice; Male; Wound Healing; Edetic Acid; Trypsin; Mice, Inbred C57BL; Bandages
PubMed: 37345866
DOI: 10.1111/exd.14857