This article aims at establishing new benchmark scenarios for Galactic cosmic-ray propagation in the GV-TV rigidity range, based on fits to the AMS-02 boron to carbon ratio (B/C) data with the usine ...v3.5 propagation code. We employ a new fitting procedure, cautiously taking into account data systematic error correlations in different rigidity bins and considering Solar modulation potential and leading nuclear cross section as nuisance parameters. We delineate specific low, intermediate, and high-rigidity ranges that can be related to both features in the data and peculiar microphysics mechanisms resulting in spectral breaks. We single out a scenario which yields excellent fits to the data and includes all the presumably relevant complexity, the BIG model. This model has two limiting regimes: (i) the SLIM model, a minimal diffusion-only setup, and (ii) the QUAINT model, a convection-reacceleration model where transport is tuned by nonrelativistic effects. All models lead to robust predictions in the high-energy regime (≳10 GV), i.e., independent of the propagation scenario: at 1σ, the diffusion slope δ is 0.43–0.53, whereas K10, the diffusion coefficient at 10 GV, is 0.26–0.36 kpc2 Myr−1; we confirm the robustness of the high-energy break, with a typical value Δh∼0.2. We also find a hint for a similar (reversed) feature at low rigidity around the B/C peak (∼4 GV) which might be related to some effective damping scale in the magnetic turbulence.
This study aimed at the development of improved drugs against human osteosarcoma, which is the most common primary bone tumor in children and teenagers with a low prognosis. New insights into the ...impact of an unconventional Pd(II) anticancer agent on human osteosarcoma cells were obtained by synchrotron radiation-Fourier transform infrared microspectroscopy and quasi-elastic neutron scattering (QENS) experiments from its effect on the cellular metabolism to its influence on intracellular water, which can be regarded as a potential secondary pharmacological target. Specific infrared biomarkers of drug action were identified, enabling a molecular-level description of variations in cellular biochemistry upon drug exposure. The main changes were detected in the protein and lipid cellular components, namely, in the ratio of unsaturated-to-saturated fatty acids. QENS revealed reduced water mobility within the cytoplasm for drug-treated cells, coupled to a disruption of the hydration layers of biomolecules. Additionally, the chemical and dynamical profiles of osteosarcoma cells were compared to those of metastatic breast cancer cells, revealing distinct dissimilarities that may influence drug activity.
Cervical cancer was considered the fourth most common cancer worldwide in 2020. In order to reduce mortality, an early diagnosis of the tumor is required. Currently, this type of cancer occurs mostly ...in developing countries due to the lack of vaccination and screening against the Human Papillomavirus. Thus, there is an urgent clinical need for new methods aiming at a reliable screening and an early diagnosis of precancerous and cancerous cervical lesions. Vibrational spectroscopy has provided very good results regarding the diagnosis of various tumors, particularly using Fourier transform infrared microspectroscopy, which has proved to be a promising complement to the currently used histopathological methods of cancer diagnosis. This spectroscopic technique was applied to the analysis of cryopreserved human cervical tissue samples, both squamous cell carcinoma (SCC) and non-cancer samples. A dedicated Support Vector Machine classification model was constructed in order to categorize the samples into either normal or malignant and was subsequently validated by cross-validation, with an accuracy higher than 90%.
Water dynamics in human cancer and non-cancer tissues Marques, M. P. M; Santos, I. P; Batista de Carvalho, A. L. M ...
Physical chemistry chemical physics : PCCP,
06/2022, Letnik:
24, Številka:
25
Journal Article
Recenzirano
Normal-to-malignant transformation is a poorly understood process associated with cellular biomechanical properties. These are strongly dependent on the dynamical behaviour of water, known to play a ...fundamental role in normal cellular activity and in the maintenance of the three-dimensional architecture of the tissue and the functional state of biopolymers. In this study, quasi-elastic neutron scattering was used to probe the dynamical behaviour of water in human cancer specimens and their respective surrounding normal tissue from breast and tongue, as an innovative approach for identifying particular features of malignancy. This methodology has been successfully used by the authors in human cells and was the first study of human tissues by neutron scattering techniques. A larger flexibility was observed for breast
versus
tongue tissues. Additionally, different dynamics were found for malignant and non-malignant specimens, depending on the tissue: higher plasticity for breast invasive cancer
versus
the normal, and an opposite effect for tongue. The data were interpreted in the light of two different water populations within the samples: one displaying bulk-like dynamics (extracellular and intracellular/cytoplasmic) and another with constrained flexibility (extracellular/interstitial and intracellular/hydration layers).
Normal-to-malignant transformation is a poorly understood process associated with cellular biomechanical properties.
A dinuclear Pt(II) complex with putrescine as bridging polyamine ligand (Pt
Put
(NH
)
Cl
) was synthesized and assessed as to its potential anticancer activity against a human non-small cell lung ...cancer line (A549), as well as towards non-cancer cells (BEAS-2B). This effect was evaluated through in vitro cytotoxicity assays (MTT and SRB) coupled to microFTIR and microRaman spectroscopies, the former delivering information on growth-inhibiting and cytotoxic abilities while the latter provided very specific information on the metabolic impact of the metal agent (at the sub-cellular level). Regarding cancer cells, a major impact of Pt
Put
(NH
)
Cl
was evidenced on cellular proteins and lipids, as compared to DNA, particularly via the Amide I and Amide II signals. The effect of the chelate on non-malignant cells was lower than on malignant ones, evidencing a promising low toxicity towards healthy cells.
In 2020, approximately 10 million people died of cancer, rendering this disease the second leading cause of death worldwide. Detecting cancer in its early stages is paramount for patients’ prognosis ...and survival. Hence, the scientific and medical communities are engaged in improving both therapeutic strategies and diagnostic methodologies, beyond prevention. Optical vibrational spectroscopy has been shown to be an ideal diagnostic method for early cancer diagnosis and surgical margins assessment, as a complement to histopathological analysis. Being highly sensitive, non-invasive and capable of real-time molecular imaging, Raman and Fourier transform infrared (FTIR) spectroscopies give information on the biochemical profile of the tissue under analysis, detecting the metabolic differences between healthy and cancerous portions of the same sample. This constitutes tremendous progress in the field, since the cancer-prompted morphological alterations often occur after the biochemical imbalances in the oncogenic process. Therefore, the early cancer-associated metabolic changes are unnoticed by the histopathologist. Additionally, Raman and FTIR spectroscopies significantly reduce the subjectivity linked to cancer diagnosis. This review focuses on breast and head and neck cancers, their clinical needs and the progress made to date using vibrational spectroscopy as a diagnostic technique prior to surgical intervention and intraoperative margin assessment.
Breast cancer is a type of cancer with the highest incidence worldwide in 2021, with early diagnosis and rapid treatment intervention being the reasons for the decreasing mortality rate associated ...with the disease. The major challenge faced by clinicians and pathologists is the lack of accuracy in the histopathological analysis of biopsy or resection samples, leading to classification misdiagnosis and compromising the prognosis of patients. Spectral histopathology has provided great advances regarding cancer diagnosis, especially through the use of FTIR spectroscopy, proving to be a valuable complement to histopathological analyses. In this study unstained formalin-fixed paraffin embedded breast cancer tissue samples, collected from patients undergoing surgery and mounted on glass slides, were probed through FTIR and Raman microspectrocopy. Two classification models were constructed using the AdaBoost algorithm, both achieving >90% accuracy and successfully discriminating invasive breast carcinoma from surrounding normal tissue. Chemical maps from the interfaces of invasive breast carcinoma-surrounding normal tissue were also generated. This study showed the potential of spectral histopathology, in particular FTIR, for daily use in pathology laboratories, introducing few disruptions to the routine workflow while increasing the sensitivity, specificity and accuracy of the diagnoses.
Breast cancer is a type of cancer with the highest incidence worldwide in 2021, with early diagnosis and rapid treatment intervention being the reasons for the decreasing mortality rate associated with the disease.
(1) Breast cancer is presently the leading cause of death in women worldwide. This study aims at identifying molecular biomarkers of cancer in human breast cancer cells, in order to differentiate ...highly aggressive triple-negative from non-triple-negative cancers, as well as distinct triple-negative subtypes, which is currently an unmet clinical need paramount for an improved patient care. (2) Raman and FTIR (Fourier transform infrared) microspectroscopy state-of-the-art techniques were applied, as highly sensitive, specific and non-invasive methods for probing heterogeneous biological samples such as human cells. (3) Particular biochemical features of malignancy were unveiled based on the cells' vibrational signature, upon principal component analysis of the data. This enabled discrimination between TNBC (triple-negative breast cancer) and non-TNBC, TNBC MSL (mesenchymal stem cell-like) and TNBC BL1 (basal-like 1) and TNBC BL1 highly metastatic and low-metastatic cell lines. This specific differentiation between distinct TNBC subtypes-mesenchymal from basal-like, and basal-like 1 with high-metastatic potential from basal-like 1 with low-metastatic potential-is a pioneer result, of potential high impact in cancer diagnosis and treatment.
Recently, some works claim that hydrophobic deep eutectic solvents could be prepared based on menthol and monocarboxylic acids. Despite of some promising potential applications, these systems were ...poorly understood, and this work addresses this issue. Here, the characterization of eutectic solvents composed of the terpenes thymol or l(−)-menthol and monocarboxylic acids is studied aiming the design of these solvents. Their solid–liquid phase diagrams were measured by differential scanning calorimetry in the whole composition range, showing that a broader composition range, and not only fixed stoichiometric proportions, can be used as solvents at low temperatures. Additionally, solvent densities and viscosities close to the eutectic compositions were measured, showing low viscosity and lower density than water. The solvatochromic parameters at the eutectic composition were also investigated aiming at better understanding their polarity. The high acidity is mainly provided by the presence of thymol in the mixture, while l(−)-menthol plays the major role on the hydrogen-bond basicity. The measured mutual solubilities with water attest to the hydrophobic character of the mixtures investigated. The experimental solid–liquid phase diagrams were described using the PC-SAFT equation of state that is shown to accurately describe the experimental data and quantify the small deviations from ideality.
Regarding the development of new antineoplastic agents, with a view to assess the selective antitumoral potential which aims at causing irreversible damage to cancer cells while preserving the ...integrity of their healthy counterparts, it is essential to evaluate the cytotoxic effects in both healthy and malignant human cell lines. In this study, a complex with two Pd(II) centers linked by the biogenic polyamine spermine (Pd2Spm) was tested on healthy (PNT-2) and cancer (LNCaP and PC-3) prostate human cell lines, using cisplatin as a reference. To understand the mechanisms of action of both cisplatin and Pd2Spm at a molecular level, Fourier Transform Infrared (FTIR) and Raman microspectroscopies were used. Principal component analysis was applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug impact. The main changes were observed between the B-DNA native conformation and either Z-DNA or A-DNA, with a higher effect on lipids having been detected in the presence of cisplatin as compared to Pd2Spm. In turn, the Pd-agent showed a more significant impact on proteins.
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