Biomolecular Concepts[JOURNAL]
Sun
200 papers
Be and Na radionuclides for a new therapy for cancer.
Kukulin VI, Bibikov AV, Tkalya EV … +2 more , Ceccarelli M, Bodrenko IV
Biomol Concepts · 2023 Jan · PMID 38167297 · Publisher ↗
B isotopes have been almost exclusively used in the neutron-capture radiation therapy (NCT) of cancer for decades. We have identified two other nuclides suitable for radiotherapy, which have ca. ten times larger cross se...
B isotopes have been almost exclusively used in the neutron-capture radiation therapy (NCT) of cancer for decades. We have identified two other nuclides suitable for radiotherapy, which have ca. ten times larger cross section of absorption for neutrons and emit heavy charged particles. This would provide several key advantages for potential NCT, such as the possibility to use a lower nuclide concentration in the target tissues or a lower neutron irradiation flux. By detecting the characteristic γ radiation from the spontaneous decay of the radionuclides, one can image their biodistribution. These advantages could open up new possibilities for NCT applications as a safer and more efficient cancer therapy.
Potential PDE4B inhibitors as promising candidates against SARS-CoV-2 infection.
Giuzio F, Bonomo MG, Catalano A … +8 more , Infantino V, Salzano G, Monné M, Geronikaki A, Petrou A, Aquaro S, Sinicropi MS, Saturnino C
Biomol Concepts · 2023 Jan · PMID 37909122 · Publisher ↗
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus belonging to the coronavirus family responsible for coronavirus disease 2019 (COVID-19). It primarily affects the pulmonary system, which is th...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus belonging to the coronavirus family responsible for coronavirus disease 2019 (COVID-19). It primarily affects the pulmonary system, which is the target of chronic obstructive pulmonary disease (COPD), for which many new compounds have been developed. In this study, phosphodiesterase 4 (PDE4) inhibitors are being investigated. The inhibition of PDE4 enzyme produces anti-inflammatory and bronchodilator effects in the lung by inducing an increase in cAMP concentrations. Piclamilast and rolipram are known selective inhibitors of PDE4, which are unfortunately endowed with common side effects, such as nausea and emesis. The selective inhibition of the phosphodiesterase 4B (PDE4B) subtype may represent an intriguing technique for combating this highly contagious disease with fewer side effects. In this article, molecular docking studies for the selective inhibition of the PDE4B enzyme have been carried out on 21 in-house compounds. The compounds were docked into the pocket of the PDE4B catalytic site, and in most cases, they were almost completely superimposed onto piclamilast. Then, in order to enlarge our study, drug-likeness prediction studies were performed on the compounds under study.
A commentary on the inhibition of human TPC2 channel by the natural flavonoid naringenin: Methods, experiments, and ideas.
Minicozzi V, Qi T, Gradogna A … +5 more , Pozzolini M, Milenkovic S, Filippini A, Ceccarelli M, Carpaneto A
Biomol Concepts · 2023 Jan · PMID 37677148 · Publisher ↗
Human endo-lysosomes possess a class of proteins called TPC channels on their membrane, which are essential for proper cell functioning. This protein family can be functionally studied by expressing them in plant vacuole...
Human endo-lysosomes possess a class of proteins called TPC channels on their membrane, which are essential for proper cell functioning. This protein family can be functionally studied by expressing them in plant vacuoles. Inhibition of hTPC activity by naringenin, one of the main flavonoids present in the human diet, has the potential to be beneficial in severe human diseases such as solid tumor development, melanoma, and viral infections. We attempted to identify the molecular basis of the interaction between hTPC2 and naringenin, using ensemble docking on molecular dynamics (MD) trajectories, but the specific binding site remains elusive, posing a challenge that could potentially be addressed in the future by increased computational power in MD and the combined use of microscopy techniques such as cryo-EM.
Modeling of olfactory transduction in AWC neuron via coupled electrical-calcium dynamics.
Nicoletti M, Luchetti N, Chiodo L … +4 more , Loppini A, Folli V, Ruocco G, Filippi S
Biomol Concepts · 2023 Jan · PMID 37574865 · Publisher ↗
Amphid wing "C" (AWC) neurons are among the most important and studied neurons of the nematode In this work, we unify the existing electrical and intracellular calcium dynamics descriptions to obtain a biophysically acc...
Amphid wing "C" (AWC) neurons are among the most important and studied neurons of the nematode In this work, we unify the existing electrical and intracellular calcium dynamics descriptions to obtain a biophysically accurate model of olfactory transduction in AWC neurons. We study the membrane voltage and the intracellular calcium dynamics at different exposure times and odorant concentrations to grasp a complete picture of AWC functioning. Moreover, we investigate the complex cascade of biochemical processes that allow AWC activation upon odor removal. We analyze the behavior of the different components of the models and, by suppressing them selectively, we extrapolate their contribution to the overall neuron response and study the resilience of the dynamical system. Our results are all in agreement with the available experimental data. Therefore, we provide an accurate mathematical and biophysical model for studying olfactory signal processing in
Effects of model membranes on lysozyme amyloid aggregation.
Burrelli A, Moretti P, Gerelli Y … +1 more , Ortore MG
Biomol Concepts · 2023 Jan · PMID 37542518 · Publisher ↗
The study of the interaction between lipid membranes and amyloidogenic peptides is a turning point for understanding the processes involving the cytotoxicity of peptides involved in neurodegenerative diseases. In this wo...
The study of the interaction between lipid membranes and amyloidogenic peptides is a turning point for understanding the processes involving the cytotoxicity of peptides involved in neurodegenerative diseases. In this work, we perform an experimental study of model membrane-lysozyme interaction to understand how the formation of amyloid fibrils can be affected by the presence of polar and zwitterionic phospholipid molecules (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [POPC] and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol [POPG]). The study was conducted above and below the critical micellar concentration (CMC) using dynamic light scattering (DLS), atomic force microscopy (AFM), UV-Vis spectrophotometry, and the quartz crystal microbalance (QCM). Our results show that the presence of phospholipids appears to be a factor favoring the formation of amyloid aggregates. Spectrophotometric and DLS data revealed that the quantity of -structure increases in the presence of POPG and POPC at different concentrations. The presence of POPG and POPC increases the speed of the nucleation process, without altering the overall structures of the fibrillar final products.
Setting up multicolour TIRF microscopy down to the single molecule level.
Schirripa Spagnolo C, Luin S
Biomol Concepts · 2023 Jan · PMID 37428621 · Publisher ↗
Investigating biological mechanisms in ever greater detail requires continuous advances in microscopy techniques and setups. Total internal reflection fluorescence (TIRF) microscopy is a well-established technique for vi...
Investigating biological mechanisms in ever greater detail requires continuous advances in microscopy techniques and setups. Total internal reflection fluorescence (TIRF) microscopy is a well-established technique for visualizing processes on the cell membrane. TIRF allows studies down to the single molecule level, mainly in single-colour applications. Instead, multicolour setups are still limited. Here, we describe our strategies for implementing a multi-channel TIRF microscopy system capable of simultaneous two-channel excitation and detection, starting from a single-colour commercial setup. First, we report some applications at high molecule density and then focus on the challenges we faced for achieving the single molecule level simultaneously in different channels, showing that rigorous optimizations on the setup are needed to increase its sensitivity up to this point, from camera setting to background minimization. We also discuss our strategies regarding crucial points of fluorescent labelling for this type of experiment: labelling strategy, kind of probe, efficiency, and orthogonality of the reaction, all of which are aspects that can influence the achievable results. This work may provide useful guidelines for setting up advanced single-molecule multi-channel TIRF experiments to obtain insights into interaction mechanisms on the cell membrane of living cells.
Head or tail? A molecular dynamics approach to the complex structure of TNF-associated factor TRAF2.
Erba F, Di Paola L, Di Venere A … +4 more , Mastrangelo E, Cossu F, Mei G, Minicozzi V
Biomol Concepts · 2023 Jan · PMID 37377424 · Publisher ↗
Tumor necrosis factor receptor-associated factor proteins (TRAFs) are trimeric proteins that play a fundamental role in signaling, acting as intermediaries between the tumor necrosis factor (TNF) receptors and the protei...
Tumor necrosis factor receptor-associated factor proteins (TRAFs) are trimeric proteins that play a fundamental role in signaling, acting as intermediaries between the tumor necrosis factor (TNF) receptors and the proteins that transmit the downstream signal. The monomeric subunits of all the TRAF family members share a common tridimensional structure: a C-terminal globular domain and a long coiled-coil tail characterizing the N-terminal section. In this study, the dependence of the TRAF2 dynamics on the length of its tail was analyzed . In particular, we used the available crystallographic structure of a C-terminal fragment of TRAF2 (168 out of 501 a.a.), TRAF2-C, and that of a longer construct, addressed as TRAF2-plus, that we have re-constructed using the AlphaFold2 code. The results indicate that the longer N-terminal tail of TRAF2-plus has a strong influence on the dynamics of the globular regions in the protein C-terminal head. In fact, the quaternary interactions among the TRAF2-C subunits change asymmetrically in time, while the movements of TRAF2-plus monomers are rather limited and more ordered than those of the shorter construct. Such findings shed a new light on the dynamics of TRAF subunits and on the protein mechanism , since TRAF monomer-trimer equilibrium is crucial for several reasons (receptor recognition, membrane binding, hetero-oligomerization).
Dipalmitoyl-phosphatidylserine-filled cationic maltodextrin nanoparticles exhibit enhanced efficacy for cell entry and intracellular protein delivery in phagocytic THP-1 cells.
Brinkhuizen C, Shapman D, Lebon A … +5 more , Bénard M, Tardivel M, Dubuquoy L, Galas L, Carpentier R
Biomol Concepts · 2023 Jan · PMID 37377352 · Publisher ↗
Vaccination through the upper respiratory tract is a promising strategy, and particulate antigens, such as antigens associated with nanoparticles, triggered a stronger immune response than the sole antigens. Cationic mal...
Vaccination through the upper respiratory tract is a promising strategy, and particulate antigens, such as antigens associated with nanoparticles, triggered a stronger immune response than the sole antigens. Cationic maltodextrin-based nanoparticles loaded with phosphatidylglycerol (NPPG) are efficient for intranasal vaccination but non-specific to trigger immune cells. Here we focused on phosphatidylserine (PS) receptors, specifically expressed by immune cells including macrophages, to improve nanoparticle targeting through an efferocytosis-like mechanism. Consequently, the lipids associated with NPPG have been substituted by PS to generate cationic maltodextrin-based nanoparticles with dipalmitoyl-phosphatidylserine (NPPS). Both NPPS and NPPG exhibited similar physical characteristics and intracellular distribution in THP-1 macrophages. NPPS cell entry was faster and higher (two times more) than NPPG. Surprisingly, competition of PS receptors with phospho-L-serine did not alter NPPS cell entry and annexin V did not preferentially interact with NPPS. Although the protein association is similar, NPPS delivered more proteins than NPPG in cells. On the contrary, the proportion of mobile nanoparticles (50%), the movement speed of nanoparticles (3 µm/5 min), and protein degradation kinetics in THP-1 were not affected by lipid substitution. Together, the results indicate that NPPS enter cells and deliver protein better than NPPG, suggesting that modification of the lipids of cationic maltodextrin-based nanoparticles may be a useful strategy to enhance nanoparticle efficacy for mucosal vaccination.
Proteins turn "Proteans" - The over 40-year delayed paradigm shift in structural biology: From to .
Frixione E, Ruiz-Zamarripa L
Biomol Concepts · 2023 Jan · PMID 37326425 · Publisher ↗
The current millennium brought up a revolutionary paradigm shift in molecular biology: many operative proteins, rather than being quasi-rigid polypeptide chains folded into unique configurations - as believed throughout...
The current millennium brought up a revolutionary paradigm shift in molecular biology: many operative proteins, rather than being quasi-rigid polypeptide chains folded into unique configurations - as believed throughout most of the past century - are now known to be intrinsically disordered, dynamic, pleomorphic, and multifunctional structures with stochastic behaviors. Yet, part of this knowledge, including suggestions about possible mechanisms and plenty of evidence for the same, became available by the 1950s and 1960s to remain then nearly forgotten for over 40 years. Here, we review the main steps toward the classic notions about protein structures, as well as the neglected precedents of present views, discuss possible explanations for such long oblivion, and offer a sketch of the current panorama in this field.
Molecular epidemiology of human papillomavirus in pregnant women in Burkina Faso.
Kabre KM, Ouermi D, Zohoncon TM … +12 more , Traore FPW, Gnoumou OPP, Ouedraogo RA, Yonli AT, Bado P, Ouedraogo P, Ouedraogo TC, Yelemkoure TE, Kuassi-Kpede PA, Obiri-Yeboah D, Ouedraogo CMR, Simpore J
Biomol Concepts · 2022 Jan · PMID 36727673 · Publisher ↗
INTRODUCTION: Genital human papillomavirus (HPV) infection is widespread among sexually active individuals. Several factors may contribute to increased risk of infection in pregnant women. The objective of this study was...
INTRODUCTION: Genital human papillomavirus (HPV) infection is widespread among sexually active individuals. Several factors may contribute to increased risk of infection in pregnant women. The objective of this study was to determine the high-risk (HR-HPV) and low-risk (LR-HPV) oncogenic HPV genotypes among pregnant women in Ouagadougou. METHODOLOGY: In this study, 100 endocervical samples were collected using a sterile swab on the sterile examination glove used during vaginal examination in pregnant women. DNA from each sample was amplified by PCR followed by hybridization using the HPV Direct Flow Chips kit detecting 36 HPV genotypes. RESULTS: Twenty-three percent (23%) of pregnant women had HPV infection. Of the 36 genotypes tested, 29 genotypes had been identified with a predominance of HPV 52 (10.34%), HPV 35 (6.89%), and HPV 82 (6.89%) for high risk and HPV 43 (10.34%), HPV 44/55 (6.90%), and HPV 62/81 (6.89%) for low risk. CONCLUSION: HPV is common among pregnant women in Burkina Faso. However, the available vaccines do not cover the frequent genotypes found in this study. HPV could therefore constitute a threat for pregnant women and a risk of infection for the newborn.
Subcellular elements responsive to the biomechanical activity of triple-negative breast cancer-derived small extracellular vesicles.
Senigagliesi B, Bedolla DE, Birarda G … +5 more , Zanetti M, Lazzarino M, Vaccari L, Parisse P, Casalis L
Biomol Concepts · 2022 Jan · PMID 36482512 · Publisher ↗
Triple-negative breast cancer (TNBC) stands out for its aggressive, fast spread, and highly metastatic behavior and for being unresponsive to the classical hormonal therapy. It is considered a disease with a poor prognos...
Triple-negative breast cancer (TNBC) stands out for its aggressive, fast spread, and highly metastatic behavior and for being unresponsive to the classical hormonal therapy. It is considered a disease with a poor prognosis and limited treatment options. Among the mechanisms that contribute to TNBC spreading, attention has been recently paid to small extracellular vesicles (sEVs), nano-sized vesicles that by transferring bioactive molecules to recipient cells play a crucial role in the intercellular communication among cancer, healthy cells, and tumor microenvironment. In particular, TNBC-derived sEVs have been shown to alter proliferation, metastasis, drug resistance, and biomechanical properties of target cells. To shed light on the molecular mechanisms involved in sEVs mediation of cell biomechanics, we investigated the effects of sEVs on the main subcellular players, i.e., cell membrane, cytoskeleton, and nuclear chromatin organization. Our results unveiled that TNBC-derived sEVs are able to promote the formation and elongation of cellular protrusions, soften the cell body, and induce chromatin decondensation in recipient cells. In particular, our data suggest that chromatin decondensation is the main cause of the global cell softening. The present study added new details and unveiled a novel mechanism of activity of the TNBC-derived sEVs, providing information for the efficient translation of sEVs to cancer theranostics.
The effects of supplementation of microalgae on biochemical, inflammatory and antioxidant responses in diabetic rats.
Fereidouni A, Khaleghian A, Mousavi-Niri N … +1 more , Moradikor N
Biomol Concepts · 2022 Jan · PMID 36315027 · Publisher ↗
Diabetes is accompanied by inflammation and oxidation. Supplementation of anti-inflammatory and antioxidant compounds can prevent the progression of diabetes. This study aimed to investigate the effects of supplementatio...
Diabetes is accompanied by inflammation and oxidation. Supplementation of anti-inflammatory and antioxidant compounds can prevent the progression of diabetes. This study aimed to investigate the effects of supplementation of microalgae (NOM) on the inflammatory and antioxidant responses in diabetic rats. Sixty male rats were divided into six groups as diabetic and non-diabetic rats receiving 0, 10 and 20 mg/kg of body weight of NOM daily for 21 days. Body weight, the serum concentrations of insulin and glucose and the tissue concentrations of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD), glutathione peroxidase (GPx) were assessed. The results showed that induction of diabetes significantly reduced the body weight, the serum concentrations of insulin and the tissue concentrations of SOD, FRAP and GPx while increasing the concentrations of glucose, MDA, IL-1β, IL-6, NF-κB and TNF-α. Daily oral administration of NOM (10 and 20 mg/kg) significantly maintained the body weight, the serum concentrations of insulin and the tissue concentrations of SOD, FRAP and GPx while preventing the increase in the concentrations of glucose, MDA, IL-1β and TNF-α. In conclusion, diabetes caused inflammation and oxidation while NOM worked as a natural anti-inflammatory and antioxidant compound.
Insights into functional connectivity in mammalian signal transduction pathways by pairwise comparison of protein interaction partners of critical signaling hubs.
Ramana CV
Biomol Concepts · 2022 Jan · PMID 36048718 · Publisher ↗
Growth factors and cytokines activate signal transduction pathways and regulate gene expression in eukaryotes. Intracellular domains of activated receptors recruit several protein kinases as well as transcription factors...
Growth factors and cytokines activate signal transduction pathways and regulate gene expression in eukaryotes. Intracellular domains of activated receptors recruit several protein kinases as well as transcription factors that serve as platforms or hubs for the assembly of multi-protein complexes. The signaling hubs involved in a related biologic function often share common interaction proteins and target genes. This functional connectivity suggests that a pairwise comparison of protein interaction partners of signaling hubs and network analysis of common partners and their expression analysis might lead to the identification of critical nodes in cellular signaling. A pairwise comparison of signaling hubs across several related pathways might reveal novel signaling modules. Analysis of rotein nteraction onnectome by enn (PIC-Venn) of transcription factors STAT1, STAT3, NFKB1, RELA, FOS, and JUN, and their common interaction network suggested that BRCA1 and TSC22D3 function as critical nodes in immune responses by connecting the signaling hubs into signaling modules. Transcriptional regulation of critical hubs may play a major role in the lung epithelial cells in response to SARS-CoV-2 and in COVID-19 patients. Mutations and differential expression levels of these critical nodes and modules in pathological conditions might deregulate signaling pathways and their target genes involved in inflammation. Biological connectivity emerges from the structural connectivity of interaction networks across several signaling hubs in related pathways. The main objectives of this study are to identify critical hubs, critical nodes, and modules involved in the signal transduction pathways of innate and adaptive immunity. Application of PIC-Venn to several signaling hubs might reveal novel nodes and modules that can be targeted by small regulatory molecules to simultaneously activate or inhibit cell signaling in health and disease.
Electrophysiological study of the effects of side products of RuBi-GABA uncaging on GABA receptors in cerebellar granule cells.
Gatta E, Bazzurro V, Angeli E … +5 more , Salis A, Damonte G, Cupello A, Robello M, Diaspro A
Biomol Concepts · 2022 Jun · PMID 35675587 · Publisher ↗
The study of the GABA receptor itself and its pharmacology is of paramount importance for shedding light on the role of this receptor in the central nervous system. Caged compounds have emerged as powerful tools to suppo...
The study of the GABA receptor itself and its pharmacology is of paramount importance for shedding light on the role of this receptor in the central nervous system. Caged compounds have emerged as powerful tools to support research in this field, as they allow to control, in space and time, the release of neurotransmitters enabling, for example, to map receptors' distribution and dynamics. Here we focus on γ-aminobutyric acid (GABA)-caged compounds, particularly on a commercial complex called RuBi-GABA, which has high efficiency of uncaging upon irradiation at visible wavelengths. We characterized, by electrophysiological measurements, the effects of RuBi-GABA on GABA receptors of rat cerebellar granule cells In particular, we evaluated the effects of side products obtained after RuBi-GABA photolysis. For this purpose, we developed a procedure to separate the "RuBi-cage" from GABA after uncaging RuBi-GABA with a laser source; then, we compared electrophysiological measurements acquired with and without administering the RuBi-cage in the perfusing bath. In conclusion, to investigate the role of the "cage" molecules both near and far from the cell soma, we compared experiments performed changing the distance of the uncaging point from the cell.
Supercomplex supercomplexes: Raison d'etre and functional significance of supramolecular organization in oxidative phosphorylation.
Nath S
Biomol Concepts · 2022 May · PMID 35617665 · Publisher ↗
Following structural determination by recent advances in electron cryomicroscopy, it is now well established that the respiratory Complexes I-IV in oxidative phosphorylation (OXPHOS) are organized into supercomplexes in...
Following structural determination by recent advances in electron cryomicroscopy, it is now well established that the respiratory Complexes I-IV in oxidative phosphorylation (OXPHOS) are organized into supercomplexes in the respirasome. Nonetheless, the reason for the existence of the OXPHOS supercomplexes and their functional role remains an enigma. Several hypotheses have been proposed for the existence of these supercomplex supercomplexes. A commonly-held view asserts that they enhance catalysis by substrate channeling. However, this - and other views - has been challenged based on structural and biophysical information. Hence, new ideas, concepts, and frameworks are needed. Here, a new model of energy transfer in OXPHOS is developed on the basis of biochemical data on the pure competitive inhibition of anionic substrates like succinate by the classical anionic uncouplers of OXPHOS (2,4-dinitrophenol, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and dicoumarol), and pharmacological data on the unique site-selective, energy-linked inhibition of energy conservation pathways in mitochondria induced by the guanidine derivatives. It is further found that uncouplers themselves are site-specific and exhibit selectivity and efficacy in the inhibition caused by the Site 1/Complex I or Site 2/Complexes II-III-selective guanidine derivatives. These results lead to new vistas and sufficient complexity in the network of energy conservation pathways in the mitochondrial respiratory chain that necessitate discrete points of interaction with classes of guanidine derivatives and uncoupling agents and thereby between Site 1 and Site 2 and the intermediate that energizes adenosine triphosphate (ATP) synthesis by Complex V. Interpretation based on Mitchell's single-ion chemiosmotic theory that postulates only a energy pool is inadequate to rationalize the data and account for the required complexity. The above results and available information are shown to be explained by Nath's theory of energy coupling and ATP synthesis, involving movement of succinate anions and protons, along with the requirement postulated by the theory for maintenance of homeostasis and ion translocation across the energy-transducing membrane of succinate monoanions and succinate dianions by Complexes I-V in the OXPHOS supercomplexes. The new model of energy transfer in mitochondria is mapped onto the solved structures of the supercomplexes and integrated into a consistent model with the three-dimensional electron microscope computer tomography visualization of the internal structure of the cristae membranes in mammalian mitochondria. The model also offers valuable insights into diseased states induced in type 2 diabetes and especially in Alzheimer's and other neurodegenerative diseases that involve mitochondrial dysfunction.
Innovative light sources for phototherapy.
Romano G, Insero G, Marrugat SN … +1 more , Fusi F
Biomol Concepts · 2022 May · PMID 35607716 · Publisher ↗
The use of light for therapeutic purposes dates back to ancient Egypt, where the sun itself was an innovative source, probably used for the first time to heal skin diseases. Since then, technical innovation and advanceme...
The use of light for therapeutic purposes dates back to ancient Egypt, where the sun itself was an innovative source, probably used for the first time to heal skin diseases. Since then, technical innovation and advancement in medical sciences have produced newer and more sophisticated solutions for light-emitting sources and their applications in medicine. Starting from a brief historical introduction, the concept of innovation in light sources is discussed and analysed, first from a technical point of view and then in the light of their fitness to improve existing therapeutic protocols or propose new ones. If it is true that a "pure" technical advancement is a good reason for innovation, only a sub-system of those advancements is innovative for phototherapy. To illustrate this concept, the most representative examples of innovative light sources are presented and discussed, both from a technical point of view and from the perspective of their diffusion and applications in the clinical field.
Quantitative active super-resolution thermal imaging: The melanoma case study.
Marini M, Bouzin M, Scodellaro R … +6 more , D'Alfonso L, Sironi L, Granucci F, Mingozzi F, Chirico G, Collini M
Biomol Concepts · 2022 Apr · PMID 35446517 · Publisher ↗
Super-resolution image acquisition has turned photo-activated far-infrared thermal imaging into a promising tool for the characterization of biological tissues. By the sub-diffraction localization of sparse temperature i...
Super-resolution image acquisition has turned photo-activated far-infrared thermal imaging into a promising tool for the characterization of biological tissues. By the sub-diffraction localization of sparse temperature increments primed by the sample absorption of modulated focused laser light, the distribution of (endogenous or exogenous) photo-thermal biomarkers can be reconstructed at tunable ∼10-50 μm resolution. We focus here on the theoretical modeling of laser-primed temperature variations and provide the guidelines to convert super-resolved temperature-based images into quantitative maps of the absolute molar concentration of photo-thermal probes. We start from camera-based temperature detection via Stefan-Boltzmann's law, and elucidate the interplay of the camera point-spread-function and pixelated sensor size with the excitation beam waist in defining the amplitude of the measured temperature variations. This can be accomplished by the numerical solution of the three-dimensional heat equation in the presence of modulated laser illumination on the sample, which is characterized in terms of thermal diffusivity, conductivity, thickness, and concentration of photo-thermal species. We apply our data-analysis protocol to murine B16 melanoma biopsies, where melanin is mapped and quantified in label-free configuration at sub-diffraction 40 µm resolution. Our results, validated by an unsupervised machine-learning analysis of hematoxylin-and-eosin images of the same sections, suggest potential impact of super-resolved thermography in complementing standard histopathological analyses of melanocytic lesions.
Corticosterone potentiates ochratoxin A-induced microglial activation.
Chansawhang A, Phochantachinda S, Temviriyanukul P … +1 more , Chantong B
Biomol Concepts · 2022 Apr · PMID 35437979 · Publisher ↗
Microglial activation in the central nervous system (CNS) has been associated with brain damage and neurodegenerative disorders. Ochratoxin A (OTA) is a mycotoxin that occurs naturally in food and feed and has been assoc...
Microglial activation in the central nervous system (CNS) has been associated with brain damage and neurodegenerative disorders. Ochratoxin A (OTA) is a mycotoxin that occurs naturally in food and feed and has been associated with neurotoxicity, while corticosteroids are CNS' physiological function modulators. This study examined how OTA affected microglia activation and how corticosteroids influenced microglial neuroinflammation. Murine microglial cells (BV-2) were stimulated by OTA, and the potentiation effects on OTA-induced inflammation were determined by corticosterone pre-treatment. Expressions of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) were determined. Phosphorylation of mitogen-activated protein kinases (MAPKs) was analyzed by western blotting. OTA significantly increased the mRNA expression of IL-6, TNF-α, IL-1β, and iNOS and also elevated IL-6 and NO levels. Corticosterone pre-treatment enhanced the neuroinflammatory response to OTA in a mineralocorticoid receptor (MR)-dependent mechanism, which is associated with increases in extracellular signal-regulated kinase (ERK) and p38 MAPK activation. In response to OTA, microglial cells produced pro-inflammatory cytokines and NO, while corticosterone increased OTA-induced ERK and p38 MAPK phosphorylation via MR. Findings indicated the direct role of OTA in microglia activation and neuroinflammatory response and suggested that low corticosterone concentrations in the brain exacerbated neurodegeneration.
The capture of host cell's resources: The role of heat shock proteins and polyamines in SARS-COV-2 (COVID-19) pathway to viral infection.
Makhoba XH, Makumire S
Biomol Concepts · 2022 Apr · PMID 35437978 · Publisher ↗
The exposure of organisms and cells to unfavorable conditions such as increased temperature, antibiotics, reactive oxygen species, and viruses could lead to protein misfolding and cell death. The increased production of...
The exposure of organisms and cells to unfavorable conditions such as increased temperature, antibiotics, reactive oxygen species, and viruses could lead to protein misfolding and cell death. The increased production of proteins such as heat shock proteins (HSPs) and polyamines has been linked to protein misfolding sequestration, thus maintaining, enhancing, and regulating the cellular system. For example, heat shock protein 40 (Hsp40) works hand in hand with Hsp70 and Hsp90 to successfully assist the newly synthesized proteins in folding properly. On the other hand, polyamines such as putrescine, spermidine, and spermine have been widely studied and reported to keep cells viable under harsh conditions, which are also involved in cell proliferation, differentiation, and growth. Polyamines are found in all living organisms, including humans and viruses. Some organisms have developed a mechanism to hijack mammalian host cell machinery for their benefit like viruses need polyamines for infection. Therefore, the role of HSPs and polyamines in SARS-CoV-2 (COVID-19) viral infection, how these molecules could delay the effectiveness of the current treatment in the market, and how COVID-19 relies on the host molecules for its successful infection are reviewed.
Diffusion of molecules through nanopores under confinement: Time-scale bridging and crowding effects via Markov state model.
Bodrenko IV, Milenkovic S, Ceccarelli M
Biomol Concepts · 2022 Apr · PMID 35417112 · Publisher ↗
Passive transport of molecules through nanopores is characterized by the interaction of molecules with pore internal walls and by a general crowding effect due to the constricted size of the nanopore itself, which limits...
Passive transport of molecules through nanopores is characterized by the interaction of molecules with pore internal walls and by a general crowding effect due to the constricted size of the nanopore itself, which limits the presence of molecules in its interior. The molecule-pore interaction is treated within the diffusion approximation by introducing the potential of mean force and the local diffusion coefficient for a correct statistical description. The crowding effect can be handled within the Markov state model approximation. By combining the two methods, one can deal with complex free energy surfaces taking into account crowding effects. We recapitulate the equations bridging the two models to calculate passive currents assuming a limited occupancy of the nanopore in a wide range of molecular concentrations. Several simple models are analyzed to clarify the consequences of the model. Eventually, a biologically relevant case of transport of an antibiotic molecule through a bacterial porin is used to draw conclusions (i) on the effects of crowding on transport of small molecules through biological channels, and (ii) to demonstrate its importance for modelling of cellular transport.
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